Clinical Trials Resource Center

New Medical Therapies™

Lung Cancer

June 23, 2014

Novartis reported phase I trial results of Zykadia (LDK378) in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). The 246 patients with ALK+ NSCLC in this single-arm study received ceritinib 750mg ALK+ daily. Findings from the study showed patients treated with ceritinib achieved an ORR of 58.5% [95% CI, 52.1-64.8%] and a median PFS of 8.2 months [95% CI, 6.7-10.1 months]. The median duration of response was 9.7 months [95% CI, 7.0-11.4 months], with a median time to first response of six weeks after starting treatment. Among 163 patients receiving 750 mg of ceritinib daily and who were previously treated with the commonly prescribed ALK inhibitor crizotinib, ORR was 54.6% [95% CI, 46.6-62.4%] and PFS was 6.9 months [95% CI, 5.4-8.4 months]. In 83 patients who had not received prior treatment with an ALK inhibitor, ORR was 66.3% [95% CI, 55.1-76.3%] and PFS had not been reached. In the 124 patients who started the study with brain metastases, ceritinib achieved an ORR of 54.0% [95% CI, 44.9-63.0%] and a median PFS of 6.9 months [95% CI, 5.4-8.4 months]. Tumor shrinkage was seen in 50.0% of patients [49 of 98 patients; 95% CI, 39.7-60.3%] with brain metastases who had received previous ALK inhibitor therapy, while 69.2% of patients [18 of 26 patients; 95% CI, 48.2-85.7%] with brain metastases who were not previously treated achieved tumor shrinkage following treatment with ceritinib.

June 2, 2014

Boehringer Ingelheim reported result of two phase III trials (LUX-Lung 3 and LUX-Lung 6) of afatinib for treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. The LUX-Lung 3 trial compared afatinib with chemotherapy (pemetrexed/cisplatin); LUX-Lung 6 evaluated afatinib v. chemotherapy (gemcitabine/cisplatin) for Asian patients. Afatinib prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of three months (27.3 to 24.3 months) and significantly reduced the risk of death by 19% (HR=0.81, p=0.037). The most pronounced reduction in risk of death was 41% (HR=0.59, CI 0.45, 0.77) in patients whose tumors have the most common EGFR mutation (exon 19 deletion of the EGFR gene); for patients with the exon 21 (L8585R) mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Those patients who continued afatinib treatment, with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment and received chemotherapy only (tumor growth was delayed by 5.6 months and 2.8 months respectively, p=0.003). This corresponded to a 40% reduction in risk of disease progression (HR=0.60). The most common adverse events in patients treated with afatinib and chemotherapy versus chemotherapy were diarrhea (53.8% v. 6.7%), hair loss or alopecia (32.6% v. 15%) and weakness or asthenia (27.3% v. 28.3%).

April 7, 2014

Novartis released results of a phase I study of LDK378 in 130 patients for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC). Of 114 ALK+ NSCLC patients treated with LDK378 at 400mg or higher per day, 80 had progressed during or following treatment with crizotinib, and 34 patients with ALK+ NSCLC were crizotinib-naive. The maximum tolerated dose observed in the study was 750mg per day. The median duration of response for the 66 responding patients treated at 400mg or higher per day was 8.2 months [95% CI; 6.9-11.4 months]. In all, 114 ALK+ NSCLC patients treated at 400mg or higher per day, median progression-free survival was 7 months [95% CI; 5.6-9.5 months]. In the 114 ALK+ NSCLC patients treated with LDK378 at 400mg or higher per day, the overall response rate (ORR) was 58% [95% CI; 48-67%] (1 complete response [CR] and 65 partial responses [PR]), which includes those patients who had progressed during or after crizotinib therapy (ORR 56% [95% CI; 45-67%]) and those who were crizotinibnaive (ORR 62% [95% CI; 44-78%]). In the 78 patients with ALK+ NSCLC who received LDK378 at the maximum tolerated dose of 750mg per day, the ORR was 59% [95% CI; 47-70%] (46 PRs), which includes those who had progressed during or after crizotinib therapy (ORR 56% [95% CI; 41-70%]) and those who were crizotinib-naive (ORR 64% [95% CI; 44-81%]). The most frequent adverse events were nausea (82%), diarrhea (75%), vomiting (65%), fatigue (47%) and increased alanine aminotransferase levels (35%). At the 750mg dose level, 50 of 81 patients (62%) required at least one dose reduction, of which 32 occurred in cycle three or later. The FDA has accepted regulatory filings for LDK378.

March 3, 2014

Eli Lilly reported results of a phase III study of ramucirumab in combination with chemotherapy in patients with second-line non-small cell lung cancer (NSCLC). The global, randomized, double-blind trial compared ramucirumab and docetaxel to placebo and docetaxel in NSCLC patients whose disease has progressed after failure of prior platinum-based chemotherapy for locally advanced or metastatic disease. Ramucirumab showed a statistically significant improvement in overall survival in the ramucirumab-plus-docetaxel arm compared to the control arm of placebo plus docetaxel, and a statistically significant improvement in progression-free survival in the ramucirumab arm compared to the control arm. The most common (>5% incidence) Grade 3 adverse events on the ramucirumab-plus-docetaxel arm were decreased white blood cell count (neutropenia/leukopenia), febrile neutropenia, fatigue/asthenia and hypertension.

September 2, 2013

Eli Lilly released results of a phase III trial of necitumumab (IMC-11F8) in combination with gemcitabine and cisplatin as a first-line treatment, as compared to chemotherapy alone, for the treatment of with stage IV metastatic squamous non-small cell lung cancer (NSCLC). The trial enrolled 1093 patients (age greater than or equal to 18 years, ECOG PS 0-2) with histologically- or cytologicallyconfirmed, stage IV squamous NSCLC, who had received no prior therapy for metastatic disease. Patients underwent radiographic assessment of disease status (computed tomography or magnetic resonance imaging) every six weeks (+/- 3 days), until radiographic documentation of progressive disease (PD). The most common adverse events occurring more frequently in patients on the necitumumab arm were rash and hypomagnesemia. Serious, but less frequent, adverse events occurring more often on the necitumumab arm included thromboembolism. Lilly plans to present results from this study at a scientific meeting in 2014, and currently anticipates submitting to regulatory authorities before the end of 2014.

August 19, 2013

Boehringer Ingelheim issued results of a phase III study of afatinib in patients with advanced non-small cell lung cancer (NSCLC). Data from the LUX-Lung 3 trial demonstrate superiority of afatinib over chemotherapy considered best-in-class (pemetrexed/cisplatin) in EGFR-mutation positive advanced NSCLC patients. Patients treated with afatinib lived for almost one year (progression-free survival (PFS) of 11.1 months) before their tumor started to grow again compared to just over half a year (PFS of 6.9 months) for those treated with chemotherapy. Patients taking afatinib with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) v. just over half a year (PFS of 6.9 months) for those in the comparator arm. Afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; P=0.007) and dyspnoea (HR, 0.68; P=0.015) and showed significantly better mean scores over time in global health status/QoL (P=0 .015) and physical (P<0.001), role (P=0.004) and cognitive (P=0.007) functioning compared with chemotherapy, as measured by standard questionnaires. The LUX-Lung clinical trial program currently involves eight studies designed to investigate the use of afatinib in various settings of advanced NSCLC, including head-to-head trials with the first-wave of reversible tyrosine kinase inhibitors.

June 24, 2013

Novartis reported results from a phase I trial of LDK378 for anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) in patients who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. This single-arm study enrolled 114 patients. The results showed an overall response rate of 60% in patients with ALK+ NSCLC taking LDK378 (750 mg/day), which includes patients who had progressed during or after crizotinib therapy (overall response rate of 59%) and those who were crizotinib-naive (overall response rate of 62%). 78 patients were treated at 750mg/day; 36 patients were treated with LDK378 at 400-750mg/day. The median duration of response for patients treated at 400mg/day or higher (n=66) was 8.2 months (95% confidence interval [CI], 6.9-NE), with a median progression-free survival of 8.6 months (95% CI; 5.7-9.9). The six-month duration of response rate at 750mg/day was 61% (95% CI; 34.9-78.8). This trial will serve as the basis for the first regulatory filing, anticipated in early 2014.

June 10, 2013

Boehringer Ingelheim issued results from a phase III trial of LUME-Lung 1 for the treatment of advanced non-small cell lung cancer (NSCLC). This randomized, openlabel, double-blind study enrolled 1,314 patients with locally advanced or metastatic (stage IIIb/IV or recurring) NSCLC after first-line therapy. The subjects received nintedanib 200mg BID plus docetaxel 75mg/m(2) once a day for three weeks (n=655), or docetaxel plus placebo (n=659). LUME-Lung 1 improved progression-free survival (PFS)—the primary endpoint—as a second-line treatment in patients with NSCLC compared to docetaxel alone. Secondary endpoints included overall survival. Results showed patients treated with nintedanib plus docetaxel lived for a median of 3.4 months before their tumor started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The most common adverse events (AEs) of any grade in the nintedanib combination and docetaxel alone groups were diarrhea (42.3% v. 21.8%, respectively) and ALT elevations (28.5% v. 8.4%, respectively). Incidence of > grade 3 AEs was 71.3% in patients treated with nintedanib plus docetaxel compared to 64.3% with docetaxel alone. A higher incidence of > grade 3 diarrhea and elevated ALT were observed in patients treated with nintedanib plus docetaxel compared to docetaxel alone (> grade 3 diarrhea: 6.6% v. 2.6%; elevated ALT: 7.8% v. 0.9%). Incidence of > grade 3 hypertension, bleeding and thrombosis were similar in both treatment arms. There was a 1% difference in discontinuation between the treatment arms, with 22.7% of patients stopping treatment with nintedanib plus docetaxel versus 21.7% with docetaxel alone.

March 4, 2013

Peregrine Pharmaceuticals issued results from a phase II trial of bavituximab for the treatment of non-small cell lung cancer (NSCLC). This Peregrine's randomized, double-blind, placebo-controlled study enrolled 121 patients with previously treated locally advanced or metastatic second-line NSCLC. Subjects received bavituximab 3mg/kg plus docetaxel or placebo plus docetaxel. Results showed a meaningful improvement in median overall survival of 11.7 months in the bavituximab plus docetaxel arm compared to 7.3 months in the control arm (HR=0.73; p value=0.217). Persistent separation in the survival curves was observed with response rates and progression-free survival also favoring the bavituximab plus docetaxel. Bavituximab was well tolerated. The most frequent adverse events were similar between both treatment arms. Based on these data, Peregrine is preparing for an end-of-phase II meeting with the FDA.

October 15, 2012

Boehringer Ingelheim released results from a phase III trial of afatinib for the treatment of non-small cell lung cancer (NSCLC). This randomized, open-label study enrolled 345 previously untreated patients with EGFR mutation positive NSCLC. Subjects received afatinib or standard chemotherapy agents (pemetrexed/cisplatin) as first-line treatment. Data showed afatinib-dosed patients had a progression-free survival (PFS) of 11.1 months versus a PFS of 6.9 months for those receiving pemetrexed/cisplatin. NSCLC patients with tumors harboring the two most common EGFR mutations (del19 and L858R) receiving afatinib had a PFS of 13.6 months versus a PFS of 6.9 months for those in the comparator arm. The afatinib-dosed arm experienced an improvement in shortness of breath, cough and chest pain, a delay in deterioration of these symptoms, and overall improved quality of life. Afatinib was well tolerated. Boehringer Ingelheim has initiated two head-to-head trials comparing afatinib to Iressa (gefitinib) and Tarceva (erlotinib), to demonstrate any potential efficacy and safety superiority.

September 17, 2012

ImmunoGen released results from a phase II trial of IMGN901, in combination with etoposide and carboplatin, for the treatment of small cell lung cancer (SCLC). This randomized, dose-finding study, NORTH, enrolled 120 patients. Subjects received etoposide 100 mg/m2 on days one through three every 21 days; carboplatin AUC5 or AUC6 on day one every 21 days; and IMGN901 ranging up to 112 mg/m2, administered on days one and eight every 21 days. Results showed that IMGN901 112 mg/m2, carboplatin AUC5 and etoposide 100 mg/m2 was the most effective dose. Of the 33 patients dosed with this regimen, 10 had an objective response and 24 (72.7%) had disease control (objective response or stable disease). IMGN901 was well tolerated. The most frequent adverse event was low grade peripheral neuropathy.

July 9, 2012

Synta Pharmaceuticals reported interim results from a phase IIb/III trial of ganetespib in combination with docetaxel for the treatment of advanced non-small cell lung cancer (NSCLC). This multi-arm, randomized, open-label phase IIb part of the GALAXY study enrolled 183 patients to date with stage IIIB/IV NSCLC who have progressed following one prior line of therapy. All subjects received a standard regimen of docetaxel 75mg/m2 on Day 1 of a 21-day cycle; subjects in the combination arm receive in addition ganetespib 150mg/m2 on Day 1 and 15. Both primary endpoints were met based on RECIST 1.1 criteria. Subjects with elevated baseline level of serum LDH (lactate dehydrogenase) who received a combination of ganetespib and docetaxel had a median PFS of 4.2 months, compared to 1.4 months in those treated with only docetaxel; subjects with a tumor KRAS mutation receiving the combination treatment had a median PFS of 4.2 months, while the docetaxel group had a PFS of 1.6 months. The treatment was well tolerated. The most frequent adverse events were neutropenia, diarrhea and fatigue. Synta Pharmaceuticals will continue to enroll more subjects in the phase IIb trial. The transition into phase III is expected later this year.

June 11, 2012

Boehringer Ingelheim issued results from a phase III trial of afatinib as a first-line treatment for stage IIIb or IV non-small cell lung cancer (NSCLC). This randomized, open-label, comparative study, LUX-Lung 3, enrolled 345 patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. Subjects received afatinib (n≡230) or pemetrexed/cisplatin (n≡115). The study met its primary endpoint of progression-free survival (PFS). In the general population, afatinib-dosed subjects averaged an 11.1 month PFS versus 6.9 months PFS for subjects dosed with pemetrexed/cisplatin. The hazard ratio was 0.58 (95% CI: 0.43-0.78) (p≡0.0004). In the sub-population of patients with the most common EGFR mutations (Del19 and L858R), afatinib-dosed subjects had a PFS of 13.6 months versus 6.9 months in the chemotherapy arm. The hazard ratio in this patient subset was 0.47 (95% CI: 0.34-0.65) (p<0.0001). The most common adverse events were diarrhea, rash and paronychia.

July 11, 2011

Oncolytics Biotech reported interim results from a phase II trial of Reolysin for non-small cell lung cancer (NSCLC). This open label trial has enrolled 22 subjects with Kras or EGFR-activated metastatic tumors, including adenocarcinoma), squamous cell carcinoma and bronchioloalveolar carcinoma. The subjects received Reolysin (3 x 1010 TCID50) intravenously daily on days one to five, in combination with carboplatin and paclitaxel. Response evaluation to date in 21 subjects showed six partial responses (28.6%), 13 subjects with stable disease (61.9%) and two with progressive disease (9.5%), for a clinical benefit rate of 90.5% and a response rate of 28.6%.

September 10, 2007

Antisoma announced positive results from a phase II trial of ASA404 for the treatment of non-small cell lung cancer. This single arm, open label extension trial enrolled 31 subjects who received 1800 mg/m2 ASA404 in combination with carboplatin and paclitaxel. Results revealed a median survival rate of 14.9 months. The median time to tumor progression was 5.5 months and the tumor response rate was 37.9%. Treatment was well generally safe and well tolerated. Based on positive phase II results, phase III trials are expected to commence in early 2008.

Poniard announced positive long-term results from a phase II trial of picoplatin for the treatment of small cell lung cancer (sclc). This open-label trial evaluated 77 subjects with platinum-refractory and resistant sclc who had relapsed within six months of first-line therapy. The subjects had a median one-year survival rate of 17.6%, compared to a median overall survival of approximately 17 to 22 weeks in subjects treated with existing second-line chemotherapies. In addition, the disease control rate was 48.1%, similar to current standard of care treatments. A phase III trial of picoplatin for small cell lung cancer is currently underway.

June 18, 2007

Genta reported positive results from a phase II trial of Ganite for the treatment of non-Hodgkin's lymphoma, at the 43rd Annual Meeting of the American Society of Clinical Oncology. This trial, dubbed GaRD, enrolled 22 subjects who had failed prior treatment with rituximab. Subjects received Ganite in combination with rituximab and dexamethasone. Overall, 41% of the subjects achieved a major objective response, including 36% with complete or unconfirmed complete responses and 5% with a partial response. Two major responders had previously failed stem cell transplantation and both sustained remission 14+ and 18+ months after their last relapse. Six subjects achieved stable disease. Of all 22 Ganite treated subjects, 46% were alive at a median follow-up of 17+ months, and 7 were currently without evidence of disease. Based on the results Genta is planning a second phase II trial evaluating Ganite in combination with another standard cancer regimen.

Sanofi Aventis and Taiho reported positive results from a phase III trial of S-1 for the treatment of gastric cancer, at the 43rd Annual Meeting of the American Society of Clinical Oncology. This randomized trial, dubbed SPIRTS, enrolled 305 subjects in Japan. Subjects were randomized to receive either oral S-1 (40 mg/m2) twice daily for 28 days followed by a 14-day rest period, or oral S-1(40 mg/m2) twice daily for 21 days plus IV cisplatin on the eighth day of treatment, followed by the 14-day rest period. The primary endpoint was overall survival (OS). Secondary endpoints included Response Rate, Time to Treatment Failure (TTF) and toxicity. Results revealed overall survival with a two-year follow-up was significantly higher in the S-1/cisplatin combination arm compared to the S-1 alone arm, with a median rate of 13 months versus 11 months, respectively (p=0.036). The overall response rate was also significantly higher in the combination arm, with 54% of subjects in the S-1/cisplatin arm showing response to treatment compared with 31.1% with S-1 alone, p=0.001). In addition, S-1 with cisplatin significantly reduced the risk of death by 22.6% (HR: 0.774; 95% CI [0.608-0.985]) over S-1 alone. Several phase III trials of S-1 are underway in the United States.

Telik reported negative top-line results from a phase III trial of Telcyta for the treatment of non-small cell lung cancer (nsclc), at the 43rd Annual Meeting of the American Society of Clinical Oncology. This randomized, active control study, dubbed ASSIST-2, enrolled 530 subjects with advanced NSCLC whose disease had progressed following first-line platinum-based therapy and a second-line treatment. The trial was designed to compare Telcyta to gefitinib. Neither the primary endpoint, superiority in overall survival, nor the secondary endpoint, superiority in progression-free survival was reached. Median survival for the Telcyta arm was 4.6 months as compared with 6.1 months for the active control arm. Median progression-free survival was 2.2 months for the Telcyta arm as compared with 2.3 months for the gefitinib arm. Telcyta is currently in phase III trials for various other indications.

February 5, 2007

Cell Genesys announced positive long-term data from a phase II trial of GVAX for the treatment of operable pancreatic cancer. This trial enrolled 60 subjects who received GVAX after surgical resection of their tumor and adjuvant radiation and chemotherapy. GVAX was administered intradermally before and after standard post-operative adjuvant radiation therapy and 5-flourouracil chemotherapy. Treatment was administered at up to five doses, the first prior to adjuvant chemoradiotherapy, the next three following adjuvant therapy at approximately one-month intervals and the fifth as a booster injection six months later. Treatment was well tolerated through the study duration. The long-term survival results revealed a median survival of 26.8 months. GVAX is currently in phase III trials for the treatment of pancreatic cancer.

Sunesis reported interim results from two phase II trials of SNS-595 for the treatment of small cell lung cancer and non-small cell lung cancer. Both trials employed a two-stage design with an interim assessment between each stage. Objective response rate, as defined by RECIST (Response Evaluation Criteria in Solid Tumors) was the determination for advancing to stage two. All subjects received SNS-595 at the MTD of 48 mg/m2 every three weeks. The small cell cancer trial included a treatment-sensitive arm and a treatment-refractory arm. Nine out of eleven evaluable subjects in the treatment-sensitive arm had stable disease or objective response by the end of two cycles of treatment, which exceeded the pre-specified requirements for advancing to stage two. In the treatment-refractory arm, none of the 20 evaluable subjects reached objective response, although there were reports of stable disease. Based on the data, enrollment in this arm was discontinued. The non-small cell cancer trial enrolled 25 subjects who had previously failed first-line treatment. Although 50% had achieved stable disease or better, objective response rates were not observed. Based on these results, enrollment was discontinued in this trial. Sunesis plans to explore additional clinical evaluation of SNS-595 in combination with other anti-cancer agents in the treatment of non-small cell lung cancer pending the full evaluation of these results.

YM BioSciences released negative results from a phase III trial of tesmilifene combined with epirubicin/cyclophosphamide for the treatment of breast cancer. This trial, conducted under a Special Protocol Assessment by the FDA, enrolled 723 women with metastatic or recurrent breast cancer. Subjects received tesmilifene combined with epirubicin/cyclophosphamide or epirubicin/cyclophosphamide alone. A planned interim analysis was conducted to determine if there was a significant difference in overall survival rates between the two treatment groups, the primary endpoint. Review of the data found that such differences had not occurred and were unlikely to occur during the course of the trial. Based on this information, YM BioSciences terminated this trial.

November 6, 2006

Vion reported positive initial results from an ongoing phase II trial of Cloretazine for the treatment of relapsed or refractory small cell lung cancer. This trial enrolled 36 subjects who were placed into one of two treatment arms, a relapsed arm and a refractory arm. Subjects initially received 125 mg/m2 of Cloretazine weekly for three weeks, every six weeks. This dose was later reduced by protocol amendment to 100 mg/m2 weekly for three weeks, every six weeks, due to significant thrombocytopenia at the initial dose level. The most commonly reported serious adverse event was Grade 3 or 4 thrombocytopenia. Of the subjects on the relapsed arm, five had a partial response and two had stable disease. Of the subjects on the refractory arm, one subject had partial response and three had stable response. Vion is continuing to accrue subjects in both arms of the trial.

June 19, 2006

Novacea announced positive results of a phase I/II trial of DN-101 (calcitriol), for the treatment of non-small cell lung cancer (NSCLC). This study enrolled patients in two stages: in the first stage, 61 subjects received on of 4 dose levels of DN-101 (from 45 mcg to 180 mcg) on day 1 plus 75 mg/m2 body surface docetaxel on day 2 in three-week dosing cycles; in the second stage, 18 subjects received escalating regimens of weekly DN-101 (190 mcg on day 1; 45 mcg to 180 mcg on day 8; 45 mcg to 180 mcg on day 15) plus docetaxel every 3 weeks. Trial data indicated that all doses of the drug were well tolerated. In the first stage, tumor response rate across all subjects was 6.6%, with a median overall survival of 6.9 months. In the second stage, median overall survival appeared to be longer with weekly dosing of DN-101; data analysis was ongoing.

February 27, 2006

CEL-SCI has announced positive results of a long-term follow-up to a phase II trial of Multikine, for the treatment of head and neck cancer. Trial data indicated that the drug extended overall survival and increased regional tumor localization at 2 years, compared to literature-established values for approved therapies. This open-label study enrolled patients with advances primary head and neck cancer, who received the drug for 3 weeks, prior to surgery or surgery plus radiation/chemotherapy (standard therapy for the disease). The company anticipated initiating phase III trials of the drug in the near future.

CuraGen issued results of a phase II trial of velafermin, for the prevention of oral mucositis (OM) due to chemotherapy/radiotherapy. Results from the study indicated that the drug failed to meet its primary efficacy endpoint, failing to establish a significant, dose-dependent trend in rates of severe OM (p>0.05). Secondary data did yield positive activity for the lowest dose of the drug, significantly reducing incidence (p=0.031) and duration (p=0.037) of severe Grade 3 or 4 adverse events, and reducing the use of antibiotics, analgesics, antiemetics and total parenteral nutrition (TPN), and reduced rates of febrile neutropenia compared, to placebo. This multi-center, dose-ranging, randomized, double-blind, placebo-controlled study enrolled 212 patients, who received one of three doses of the drug (0.03 mg/kg, n=50; 0.1 mg/kg, n=56; and 0.2 mg/kg, n=55) or placebo (n=51). Based on these results, the company announced plans to initiate a phase II study of the low dose of the drug in Q2 2006, with preliminary results expected in Q3 2007.

Introgen reported positive results of a phase I/II trial of INGN 225, for the treatment of advanced small cell lung cancer in the journal Clinical Cancer Research. Trial data yielded a 62% objective tumor response rate for subjects receiving the drug in combination with chemotherapy, compared to a literature-established baseline of 5-25%. Further, 75% of subjects who experienced a p53 immune response (the drug's targeted mechanism of action) experienced objective clinical responses and increased overall survival. This open-label study enrolled second-line patients at the H. Lee Moffitt Cancer Center.

January 2, 2006

Pharmacyclics announced top-line results of a phase III trial of Xcytrin (motexafin), for the treatment of brain metastases in subjects with non-small cell lung cancer (NSCLC). Trial data failed to demonstrate significant improvement in time to neurological progression (15.4 months vs. 10.0 months for placebo; p=0.122). Further, no improvements were noted in overall survival or several other secondary endpoints, though reduction in steroid use trended positively. North American subjects did yield significant improvements (24.2 months vs. 8.8 months; p=0.004). This randomized, controlled study enrolled 554 patients across 94 site in North America, Europe and Australia.

November 28, 2005

Ariad Pharmaceuticals issued positive interim results of a phase Ib trial of an orally administered formulation of AP12573, their investigational mTOR inhibitor for the treatment of solid tumors. Data from the first 45 patients yielded a positive oral-dose tolerability profile across three daily dosing regimens: continuous daily dosing; dosing for 3 of every 4 weeks; and dosing for 4 of every 7 days. Maximum tolerated dose was reached in each of the first two regimens (10 mg and 15 mg daily, respectively), with oral mucositis noted as the dose limiting toxicity for each indication; dose-escalation was ongoing in the third group, and had reached doses of 40 mg daily on treatment days. This open-label dose- escalation had enrolled 58 subjects to date. The company announced plans to initiate investigation of additional regimens of the drug.

CuraGen and TopoTarget announced positive interim results of a phase I trial of PDX101, their histone deacetylase inhibitor for the treatment of solid tumors. Pharmacokinetic data yielded a dose-related absorption profile across trial regimens, and an elimination half-life of approximately 1 hour. Dose-proportional bioactivity was noted in histone hyperacetylation, which lasted 6-24 hours. Oral bioavailability was approximately 33%. No serious hematological toxicities were noted. This ongoing open-label dose-escalation study enrolled 42 patients with advanced refractory solid tumors, who received intravenous or orally available formulations PXD101 monotherapy. Based on these data, the company selected a dose of 1000 mg/m2 for use in upcoming phase II trials. Additional results of the study were to be presented at the annual meeting of the American Society of Hematology in December.

Point Therapeutics issued positive results of a phase II trial of talabostat for the treatment of non-small cell lung cancer (NSCLC). The drug produced an objective response rate (defined as a reduction in tumor size of at least 50%) of 11.9% (n=5/42); this included 3 partial responses and 2 ongoing complete responses (since March and April 2005). Median progression-free survival was 4.2 months, and median overall survival was 8.4 months; among the 31 patients enrolled in the study for at least a year, one-year survival rate was 48%. This open-label study enrolled 42 evaluable patient with relapsed or refractory NSCLC (64% second line, 36% third line or later; 75% failing a prior platinum/taxane regimen), who received talabostat in combination with docetaxel.

October 10, 2005

OXiGENE announced positive results of a phase Ib/II trial of their Combretastatin A4 Phosphate (CA4P), for the treatment of non-small cell lung cancer (NSCLC), at the 1st National Cancer Research Institute Cancer Conference in Birmingham, UK. Data from the first 12 subjects indicated that weekly drug administration produced a significant and sustained 40% reduction in tumor blood flow at 3 weeks, following radiation therapy. Median survival in subjects receiving weekly doses of the drug appeared to be longer than for subjects receiving the single-dose (11.6 months vs. 6.8 months), though these data were still preliminary. This ongoing open-label study enrolled 28 NSCLC patients, who received either a single-dose of CA4P (50 mg/m2) or weekly doses at the same dose level in combination with radiation therapy (27 Gray in 6 fractions) over 3 weeks.

August 15, 2005

Novelos has announced positive results of a phase I/II trial of NOV-002, for the treatment of non-small cell lung cancer. The drug is currently approved in Russia, where it is marketed as Glutomix. Intent-to-treat analysis indicated that 69% (11/16) of subjects receiving intravenous (IV) and subcutaneous (SC) NOV-002 in combination with chemotherapy achieved objective (complete or partial) tumor response, vs. 33% (5/15) receiving chemotherapy alone (p=0.044). Subjects receiving NOV-002 via IV and intramuscular (IM) injection plus chemotherapy experienced a non-significant 46% (6/13) objective response rate. The drug also produced improved tolerance of chemotherapy in both dosing groups, with 100% of the IV/SC and 85% of the IV/IM subjects completing 4 cycles of chemotherapy, vs. 50% of subjects receiving chemotherapy alone (p=0.004). This randomized, controlled study enrolled 44 patients, who received one of two regimens of NOV-002 (IV/SC or IV/IM) plus chemotherapy or chemotherapy alone for 6 months. The company announced plans to initiate phase II/III trials of the drug in 2006, based on these results.

July 18, 2005

Aphton reported positive results of a phase I trial of their anti-Lewis Y tumor-associated antigen monoclonal antibody IGN311, for the treatment of solid tumors. Data yielded a positive safety profile, with no adverse events reported for the low and middle dose regimens and 1 event (nausea & vomiting) noted in the high dose regimen. Pharmacokinetic results indicated a mean serum half-life of at least 20 days. Preliminary efficacy results demonstrated a reduction in the number of circulating Lewis-Y-positive tumor cells in those patients with detectable levels of these cells prior to treatment. This open-label dose- escalation study enrolled 12 subjects with Lewis Y positive epithelial tumors (breast, colorectal, gastric and pancreatic). Subjects received one of three doses of the drug (50 mg, n=3; 100 mg, n=3; or 200 mg, n=6) on days 1 and 15 of the study period. The company announced plans to initiate additional trials of the drug in the near future.

Genentech and OSI Pharmaceuticals announced that results of a phase III trial of their approved EGFR inhibitor Tarceva (erlotinib), for the treatment of non-small cell lung cancer (NSCLC), have been published in the New England Journal of Medicine. Results from the study indicated that Tarceva produced a 8.9% overall response rate, compared to <1% for placebo (p<0.001); median response durations were 7.9 months and 3.9 months, respectively. Progression free survival was also improved to 2.2 months, compared to 1.8 months for placebo (p<0.001), and overall survival, the primary endpoint, was 6.7 months, vs. 4.7 months for placebo, a reduction in mortality risk of 30% (p<0.001). Finally, 1 year survival rates also improved (31% vs. 22%, respectively). This double- blind, placebo-controlled study enrolled 731 NSCLC patients who had failed 1 or 2 prior chemotherapy regimens across 86 sites in 17 countries. Subjects were randomized 2:1 to receive 150mg Tarceva or placebo daily.

July 11, 2005

Human Genome Sciences reported positive results of a phase II trial of their investigational monoclonal antibody HGS-ETR1 (mapatumumab), for the treatment of non-small cell lung cancer (NSCLC), at the 11th World Conference on Lung Cancer in Barcelona, Spain. Results from the study indicated that the drug produced stable disease in 29% of subjects (n=9), with 8 subjects undergoing at least 4 treatment cycles. Safety data indicated no incidence of immunologic response, no discontinuations due to drug-related toxicity, and an overall positive tolerability profile for the 21-day 10 mg/kg dosing cycles. This multi-center, open-label study had enrolled 32 heavily pretreated NSCLC patients to date in the US, who received intravenous infusions of 10 mg/kg HGS-ETR1 every 21 days apart in the absence of disease progression.

Telik issued interim results of a pair of phase II trials of Telcyta (TLK286), for the treatment of NSCLC, at the 11th World Conference on Lung Cancer. In the first study, objective tumor response was noted in 58% of subjects (15 of 26) receiving Telcyta in combination with carboplatin and paclitaxel, including 1 complete response and 14 partial responses; disease stabilization rate, including objective responses, was 92%. This multicenter study was to be enlarged to confirm these positive results. In the second study, Telcyta in combination with cisplatin was shown to produce objective response in 32% of subjects (8 of 25), with an 88% disease stabilization rate. Both these ongoing studies investigated Telcyta in combination with standard chemotherapeutics for the first-line treatment of NSCLC.

May 23, 2005

Cell Therapeutics issued positive preliminary results of a phase II trial of Xyotax (paclitaxel poliglumex), for the first-line treatment of ovarian cancer. Results from the induction phase of the study indicated that the drug produced an 85% complete response rate, with an additional 12% of subjects experiencing partial response. This 98% response rate was superior to a historical baseline response rate of 80%. This open-label study enrolled 82 patients with treatment naíve stage III/IV ovarian cancer, who received Xyotax in combination with carboplatin on day 1 of a 21 day cycle for 6 cycles.

GTx reported positive results of a phase IIb trial of Acapodene (toremifene citrate), for the prevention of prostate cancer. The drug was previously approved as a treatment for advanced breast cancer. Trial data indicated efficacy in the trial's primary endpoint, producing a 48% reduction in prostate cancer incidence at 12 months in the lowest dosing group, vs. placebo (p=0.45). The higher two dosing groups both produced non- significant reductions in disease incidence. This 4- arm, double blind, placebo-controlled study enrolled 514 patients with high grade prostatic intraepithelial neoplasia (a prostate cancer risk factor) across 64 US sites, who received one of 3 oral doses of Acapodene (20 mg, 40 mg or 60 mg) or placebo once daily for one year.

Regeneron announced preliminary results of a phase I trial of VEGF Trap, for the treatment of advanced cancers. The drug's overall safety profile was positive, with most toxicity issues observed to be mild to moderate, though occasional incidence of serious adverse reactions, including hypertension, was observed. Maximum tolerated dose had not yet been reached. Preliminary evidence of biological activity and efficacy were observed, with VEGF Trap administration producing rapid tumor vascular response and some evidence of efficacy (1 partial response, 2 minor responses and 1 stable disease). This open-label single-agent study had enrolled 27 patients to date, who received one of five dose levels of the drug.

Schering and Novartis reported preliminary results of their phase III "CONFIRM-1" trial of PTZ/ZK (vatalinib), for the treatment of colorectal cancer. Trial data failed to meet their primary endpoint, with the drug producing a non-significant 12% decrease in risk of disease progression (p=0.118), as assessed by central data review. Secondary efficacy was noted, with investigator review producing a 17% reduction in risk of progression (p=0.026); higher efficacy was also noted among subjects with high levels of serum lactate dehydrogenase. Overall tolerability was generally positive, with adverse events generally similar to other VEGF inhibitors. This randomized, double-blind, placebo-controlled study enrolled 1168 subjects, who received an oral dose of either 1250 mg PTK/ZK or placebo once daily, in combination with standard FOLFOX4 chemotherapy. The companies announced that these data, in combination with upcoming data from their CONFIRM-2 phase III trial, would form the basis of regulatory submission in early 2007.

Transgene issued positive results of a phase II trial of their investigational vaccine candidate MVA-MUC1- IL2, for the treatment of non-small cell lung cancer (NSCLC). Trial data yielded preliminary evidence of efficacy, with 37% of subjects experiencing a partial response (PR), 71% of subjects achieving stable disease (PR or stable disease), median time to progression of 6.4 months, median survival of 13 months, and a 53% 1 year survival rate. Furthermore, subjects demonstrating immune response against the MUC1 tumor protein experienced significantly better overall survival (p=0.0035). This open-label study enrolled 44 patients with stage IIIB/IV NSCLC, who received MVA-MUC1-IL2 in combination with cisplatin and vinorelbine chemotherapy.

May 2, 2005

Point Therapeutics has announced results of a phase II trial of their investigational orally active irreversible dipeptidyl peptidase IV inhibitor talabostat, for the treatment of non-small cell lung cancer (NSCLC). Results from the study indicated that the drug, in combination with the chemotherapeutic docetaxel, met the study's primary endpoints of improving overall tumor response vs. docetaxel alone. This single-arm, two-stage study enrolled patients with stage IIIb/IV NSCLC whose tumors were refractory to a platinum-based first-line chemotherapy regimen. The company announced plans to present expanded results of the study at the 41st Annual Meeting of the American Society of Clinical Oncology in May, and to initiate phase III trials of the drug later in 2005.

April 25, 2005

Adventrx Pharmaceuticals reported results of a phase II trial of CoFactor (CH2FH4), in combination with 5- fluorouracil (5-FU), for the treatment of colorectal cancer. Toxicity and pharmacodynamic data indicated a positive toxicity profile based on a laboratory measures. Specifically, administration of CoFactor produced an increase producing increases in RBC folate pool expansion (form a mean baseline score of 533 ng/ml to a score of 1295 ng/ml following weekly dosing), urinary folate excretion (an indication of formaldehyde toxicity) showed a small decrease (from a baseline historical baseline of 5 ug/ml to a post-treatment mean of 3.7 ug/ml). These data support the use of CoFactor in combination with 5-FU to improve efficacy and reduce toxicity. This open-label study enrolled subjects with metastatic colorectal cancer, and was designed to investigate several laboratory measures of the toxicity associated with CoFactor administration and metabolism, in the hopes that the drug in combination with 5-FU will provide better efficacy and reduced toxicity, compared to standard therapy of 5-FU and leucovorin. The company announced that these data would serve to support upcoming phase IIb and III trials in the UK and the US.

Agennix reported positive results of a phase II trial of talactoferrin alpha in combination with chemotherapy, for the first line treatment of non-small cell lung cancer (NSCLC). Results from the study found that the addition of talactoferrin significantly improved overall response rate vs. placebo. Specifically, overall response rate in the prospectively defined evaluable patient group was 47%, vs. 29% for placebo (p= 0.05). The addition of talactoferrin was also well tolerated, with no evidence of increased toxicity. This double-blind, placebo- controlled study enrolled 110 treatment-naïve NSCLC patients, who were randomized 1:1 to receive talactoferrin or placebo, in combination with a standard chemotherapeutic regimen of carboplatin/paclitaxel.

Human Genome Sciences reported positive results of an ongoing phase I trial of their investigational TRAIL-1 monoclonal antibody HGS-ETR1, for the treatment of solid tumors. Trial data met their safety endpoints, with the highest dose acceptably tolerated and a generally mild (Grade 1 or 2) adverse event profile. Pharmacokinetics were proportional to dose, and mean elimination half-life was 17 days. Efficacy was also noted, with 10 instances of stable disease, including one subject who had received 16 treatments with the drug. This open-label, multi-center, dose- escalation trial had enrolled 44 heavily pretreated subjects to date (median prior chemotherapeutic regimens: 6), who received one of 7 IV doses of the drug (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg), once every 14 or 28 days.

Medarex and Bristol-Myers Squibb reported positive results of a phase II study of their investigational two-drug therapy for metastatic melanoma, which includes the anti-CTLA-4 antibody MDX-010 and the gp100 melanoma vaccine MDX-1379. Both trial dosing regimens yielded evidence of efficacy, with 2 complete responses (ongoing through 30 and 31 months) and 2 partial responses (4 months; ongoing through 34 months) in cohort 1, and 3 partial responses (6 months; ongoing through 25 and 26 months) in cohort 2. Serious Grade III/IV adverse events occurred more often in cohort 1 (n=9) than cohort 2 (n=5). This two- armed open-label study enrolled 56 subjects with metastatic melanoma, who received MDX-1379 plus 3.0 mg/kg MDX-010 every 3 weeks (cohort 1; n=29), or MDX-1379 plus an initial 3.0 mg/kg dose of MDX-010, followed by 1.0 mg/kg every 3 weeks (cohort 2; n=27).

April 4, 2005

Ligand Pharmaceuticals reported negative results of a pair of phase III trials of Targretin (bexarotene), their retinoid X receptor modulator, for the first-line treatment of non-small cell lung cancer (NSCLC) in combination with chemotherapy. Both trials failed to meet the primary endpoint of improved overall survival, with no significant difference observed between subjects receiving Targretin combination therapy and subjects receiving chemotherapy alone. Further, neither trial produced evidence of efficacy in the secondary endpoint, improvements in Kaplan-Meier projected two-year survival. Both trials were dual arm studies which enrolled subjects across sites worldwide. In both studies, patients were randomized to receive either standard chemotherapy (cisplatin/vinorelbine in the first, carboplatin/paclitaxel in the second) alone or in combination with oral doses of Targretin. Based on these results, Ligand announced plans to shift the development focus for Targretin to second- and third-line NSCLC indications.

December 6, 2004

Genentech reported positive results of a phase III study of Avastin (bevacizumab), their monoclonal antibody approved for the treatment of non-small cell lung cancer, for the treatment of colorectal cancer. Interim results indicated that the addition of Avastin to a standard chemotherapy regimen produced a 26% reduction in the risk of death, compared to chemotherapy alone. Furthermore, the drug produced a 17% improvement in median survival time (12.5 vs. 10.7 months). This randomized, controlled, multicenter trial enrolled 829 patients with advanced refractory colorectal cancer, who received a standard FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin) with or without Avastin. Genentech announced that they planned to discuss filing of an sBLA with the FDA based upon these results.

Genmab has announced positive preliminary results from a phase I/II trial of HuMax-EGFr, for the treatment of head and neck cancer. The trial used two neural imaging techniques to examine tumor size and function following 4 weekly doses of the drug. The first technique, which measured disease state by metabolic activity, found that of the 15 subjects evaluable by this method, 6 showed a partial metabolic response (PMR) and 3 patients out of the 15 showed a stable metabolic disease (SMD). All patients showing response were in one of the three highest dose cohorts, and all subjects in the two highest dose cohorts experienced either PMR or SMD. The second imaging technique, which measured tumor size, found that of the 16 patients evaluable by this method, 2 showed a partial response (PR) and 8 showed stable disease (SD). All responses occurring in one of the four highest dose groups, and six out of 7 patients in the two highest groups obtained a PR or SD. This open-label study enrolled a total of 17 subjects, who were randomized to receive a single-treatment of one of six doses of the drug (0.15, 0.5, 1, 2, 4 or 8 mg/kg), followed by a 28 day safety washout and subsequent treatment once weekly for 4 weeks at the same dose. The company announced that they expected additional data from the trial in 2005.

Point Therapeutics has announced positive interim results of a phase II trial of talabostat (PT-100), for the treatment of refractory non-small cell lung cancer (NSCLC). Data from the first 20 subjects met their interim efficacy requirements, with 2 subjects experiencing a reduction in tumor size of 50% or greater. Additional efficacy was observed in the secondary endpoint, with a median time to tumor progression of 24 weeks, compared to a historical baseline of 14. This open-label study plans to enroll a total of 41 patients with unresectable NSCLC, all of whom will receive daily oral talabostat for 2 weeks, following a standard dose of the chemotherapeutic taxotere. Achievement of this interim milestone allows the company to continue enrolling patients up to the full planned cohort size.

November 8, 2004

Biomira and Merck have announced positive results of a phase II b trial of BLP 25, their investigational liposomal vaccine for the treatment of non-small cell lung cancer (NSCLC). Trial data demonstrated that the drug produced significant increases in median patient survival time, including a 4.4 month extended benefit in patients receiving L-BLP25 after having achieved either stable disease or a response to first line chemotherapy. Overall median survival for the cohort receiving the vaccine was 17.4 months, versus 13 months for the control group. Benefit was also seen in the number of patients achieving two year survival in the vaccine cohort than in the standard control group (43.2% vs., 28.9%), and in maintenance of quality of life measures. This randomized, standard-therapy-controlled study enrolled 171 first-line-relapsed or refractory NSCLC patients, who received a single low-dose of intravenous cyclophosphamide three days prior to the first vaccination dose; vaccinations were given weekly for the first eight weeks and at six-week intervals thereafter. Quality of life and clinical assessments took place at Week 4, Week 8 and then at 12-week intervals for the remainder of the trial. The companies announced plans to continue development of the drug in additional trials.

October 4, 2004

Ariad Pharmaceuticals reported interim results of a pair of phase I single-agent study of AP23573, their mTOR inhibitor for the treatment of solid tumors. Trial results showed to drug to be efficacious in treating solid tumors, with 49% (24 of 49) of subjects demonstrating a tumor response; this included 9 partial responses (reduction of tumor size by at least 30%), 5 partial responses (reduction of tumor size by 15%-29%), and 14 disease stabilizations. Median response was 5 months, with some responses extending to 18 months. The drug was well tolerated in both trials, with oral mucositis observed as the dose limiting toxicity. The two trials have to date enrolled a total of 49 subjects with mixed solid tumors; 27 subjects in a daily-dosing investigation and 22 subjects on a weekly-dosing regimen. Both trials are ongoing.

Bayer Pharmaceuticals and Onyx Pharmaceuticals reported the results of a phase II single-agent study of BAY43-9006, their RAF kinase/VEGFR inhibitor being investigated for the treatment of advanced hepatocellular carcinoma (HCC), at the 16th meeting of the American Association for Cancer Research – National Cancer Institute – European Organization for Research and Treatment of Cancer in Geneva, Switzerland. Results of the trial indicated that the drug demonstrated significant efficacy, with 43% of subjects demonstrating 4-month stable disease state, 4% of subjects demonstrating a reduction in tumor size of 25% to 50%,and 5% of subjects demonstrating tumor shrinkage of 50% or more. Median survival rate for all subjects was 9.2 months, and median time to progression was 4.2 months. The open label study enrolled a total of 137 treatment-naïve patients with advanced HCC, all of whom received 400 mg. twice daily in continuous 4-week regimens. Based on this data, the companies announced plans to initiate a phase III single-agent trial, as well as a phase II chemotherapy adjuvant trial.

Epimmune Inc. announced positive combined results of two phase I trials of their multi-epitope cancer vaccine candidate EP-2101, for the treatment of non-small cell lung cancer (NSCLC) and colorectal cancer. Preliminary efficacy data have indicated that the vaccine is strongly immunogenic, with 93% of subjects demonstrating immunological response to at least 1 of the 9 antigenic vaccine components, 53% of subjects demonstrating response to 5 of the 9, and a median response to 4 of the 9. The vaccine was safe and well tolerated. The trials enrolled a total of 24 subjects with stage IIB/IIIA NSCLC or stage III colorectal cancer, all of whom received a total of 6 treatments with the vaccine, once every three weeks for 18 weeks. Following the results of these two investigations, Epimmune announced plans for the initiation of a phase II trial in NSCLC, to be initiated by the end of 2005.

June 14, 2004

Aesgen reported positive results of their phase III study of Saforis (L-glutamine) for the treatment of oral mucositis in cancer patients receiving chemotherapy. Results showed that Saforis significantly reduced the severity and duration of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy regimens versus placebo. Utilizing two sequential treatment cycles, subjects received either Saforis-then-placebo or placebo-then-Saforis. In the first cycle, Saforis subjects showed a 22% reduced incidence of moderate-to-severe oral mucositis, and when this group was switched to placebo during the second treatment cycle, incidence of oral mucositis was 36% below baseline. The multi-center study enrolled 326 evaluable subjects. Based on these results, Aesgen announced plans to file a NDA under their Fast Track designation in the near future.

GlaxoSmithKline reported positive interim results of their phase II study investigating lapatinib, an inhibitor of two receptor tyrosine kinases (ErbB1/EGFR and ErbB2), for the treatment of refractory metastatic breast cancer. Preliminary results from the first 41 subjects indicated that a once daily oral dose of lapatinib might effect an improved or stable disease state in women with breast cancer refractory to standard treatment regimens including Herceptin (trastuzumab). The study found that 46% (n=19) of the evaluated patients had stable or improved disease state at 8 weeks, and 24% (n=10) at 16 weeks. The ongoing multi-center, open label study plans to enroll a total of 80 women with breast cancer over-expressing ErbB2, all of whose disease had been refractory to treatment regimens including Herceptin, an FDA approved monoclonal ErbB2 antibody. If final results confirm the interim analysis, GlaxoSmithKline plans to use this trial to support ongoing trials of lapatinib in multiple ErbB2-expressing solid tumors.

ImClone Systems and Merck KGaA reported negative results from a phase III trial investigating IMC-BEC2, an anti-idiotypic monoclonal antibody cancer vaccine for the treatment of small cell lung cancer (SCLC). Results showed the vaccine trial did not meet its primary endpoint of survival. The international, randomized study was designed to assess the survival benefit of vaccination with IMC-BEC2 and the immune stimulant BCG over a two-year period. Subjects received IMC-BEC2/BCG vaccination or were only monitored in the observation arm. The study was conducted in collaboration with the European Organization for Research and Treatment of Cancer. Both companies intend to meet to discuss the future of the IMC-BEC2 development program.

OncoGenex and Isis announced positive results of a phase I study of OGX-011, an antisense clusterin inhibitor, for the treatment of prostate cancer. Results indicated that the drug achieved high concentration in target tissues and successfully dose-dependently down-regulated the expression of clusterin, a cell survival mediator. The study was designed to assess the bioavailability, tissue specificity and optimum dosing regimen of weekly IV infusions of OGX-011 in subjects with localized prostate cancer over 4 weeks. Immunostaining revealed availability of OGX-011 in the target tissue, and a 91% reduction in clusterin at the highest dose level (640 mg); this dose was determined to be optimum for future studies. The study enrolled a total of 25 subjects eligible for prostatectomy, all of whom underwent the surgery following the trial. OncoGenex and Isis planned to use the dosing information obtained in this trial to support the initiation of a phase II study later this year.

Therion Biologics reported results from two phase I trials investigating PANVAC-VF, a therapeutic cancer vaccine for the treatment of pancreatic cancer. The subcutaneously administered vaccine is designed to stimulate the immune system to target and destroy cancer cells expressing the carcinoembryonic antigen (CEA) and mucin -1 (MUC-1). Results showed a median overall survival of 7.9 months and at least 5.3 months, respectively, compared to an historical median overall survival of approximately 3.0 months. In addition, 33% of subjects in the study remain alive at 13 months. No serious adverse events related to the vaccines were reported. Common side effects included fever, chills and fatigue. The open label studies enrolled a total of 22 subjects with advanced (Stage III or IV) pancreatic cancer who had received prior chemotherapy. Due to these positive results, Therion will conduct a pivotal phase III trial with PANVAC-VF in the summer of 2004.

May 10, 2004

OSI Pharmaceuticals, Genentech and Roche reported positive results from a phase III trial investigating Tarceva (erlotinib), a HER1/EGFR-inhibitor for the treatment of non-small cell lung cancer (NSCLC). Results showed the trial met its primary endpoint of improving overall survival. Data showed secondary endpoints were met, which included improving time to symptomatic deterioration, progression-free survival and response rate. Adverse events reported included mild to moderate diarrhea and rash. The worldwide, multi-center, randomized, controlled study enrolled subjects with stage IIIB/IV recurrent NSCLC who had at least one, but no more than two prior chemotherapy regimens. Results will be reported at the 2004 Annual Meeting of the American Society of Clinical Oncology (ASCO) in New Orleans. OSI plans to submit an NDA for Tarceva during the summer of 2004.

April 12, 2004

Biomira and Merck KGaA reported preliminary results from a phase IIb trial investigating BLP25, a synthetic MUC1 peptide vaccine for the treatment of non-small cell lung cancer (NSCLC). Results, although not statistically significant, did show that subjects given the vaccine had a median survival that was 4.4 months longer than with control. The observed two-year survival for subjects with locoregional Stage IIIb disease was 60% for the vaccine arm compared with 36.7% for the control arm. The controlled, randomized, open-label enrolled 171 subjects with Stage IIIb and IV NSCLC.

January 26, 2004

Pharmacyclics reported positive results from a phase III trial investigating Xcytrin (motexafin gadolinium) in combination with whole brain radiation therapy (WBRT) for the treatment of brain metastases in lung cancer patients. Results showed that Xcytrin significantly prolong the time to neurologic progression, determined by investigators and a review committee The randomized, controlled trial enrolled 401 subjects with metastatic cancer to the brain and was designed to compare the effects of WBRT alone to WBRT plus Xcytrin. Results were reported in the January issue of the Journal of Clinical Oncology (JCO). Based on these results, Pharmacyclics initiated a pivotal phase III trial, called SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) in the U.S., Canada, Europe and Australia.

October 27, 2003

Astrazeneca reported final results from a pivotal phase II trial investigating Iressa (gefitinib), an approved drug for the treatment of non-small cell lung cancer. Results showed that 12% of subjects who received Iressa (250 mg),once daily, demonstrated at least a 50% reduction in tumor size. Further analysis showed a tumor response rate of 13.6% at the recommended dose of 250 mg and 10.6% overall for both doses tested. The median duration of response was 7 months. The double-blind, randomized study enrolled 216 subjects who had previously received two or more types of chemotherapy. Iressa is approved in the U.S. for use as monotherapy for the treatment of advanced non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapy. Results were reported in October 2003 in The Journal of the American Medical Association.

GlycoGenesys reported positive results from a phase I trial investigating GSC-100, a Galectin-3 targeting agent for the treatment of various cancers. Results showed that five (41.7%) subjects achieved stable disease for at least three months. One subject still remains on GCS-100 after 18 months of treatment and has achieved a partial response. GCS-100 was well tolerated with no dose-limiting toxicity observed. A maximally tolerated dose was not reached at dose levels up to 80 mg/m2. The open-label, dose escalation study enrolled 12 subjects and was designed to test the drug on subjects with unresectable, relapsed, or refractory advanced solid tumors for which there is no curative therapy. GCS-100 was administered intravenously, twice weekly, at doses of 30, 42.5, 60 or 80 mg/m2 for up to six, four-week treatment cycles, or six months.

October 6, 2003

Genentech and Roche reported negative results from a phase III trial investigating Tarceva (erlotinib), an epiderma factor 1 chemotherapy aid for the treatment of non-small lung cancer. Results showed the trial did not meet the primary endpoint of improving overall survival. One of the secondary endpoints, time to symptomatic progression, did achieve statistical significance, but did not improve overall survival or time to disease progression. The multi-center, randomized, controlled, U.S. study, called TRIBUTE, enrolled 1,050 subjects with metastatic non-small cell lung cancer. Subjects received Tarceva at 150 mg/day in combination with standard chemotherapy (carboplatin and paclitaxel).

August 18, 2003

Seattle Genetics reported positive results from an ongoing phase II trial investigating SGN-15, an antibody-drug conjugate for the treatment of non-small cell lung cancer. Preliminary results demonstrated a median survival of 11.4 months for subjects given SGN-15 plus Taxotere compared to 5.1 months with Taxotere alone. Progression free and overall survival data were analyzed using modified intent to treat methodology. Progression-free survival data showed a median of 14.9 weeks for subjects given the combination of SGN-15 plus Taxotere versus a median of 7.9 weeks with Taxotere alone. Data also showed a disease control rate, defined as the percentage of evaluable patients demonstrating a complete response, partial response or stable disease, of 61% in the combination arm compared to 39% in the Taxotere-only arm. The study enrolled 62 subjects and was designed to evaluate the safety of SGN-15 in combination with Taxotere in subjects who failed at least one prior therapy. Results were reported at the 10th World Conference on Lung Cancer in Vancouver.

Titan Pharmaceuticals reported positive results from a phase II trial investigating Pivanex, a histone deacetylases inhibitor for the treatment of non-small cell lung cancer. Results showed that eight of the eleven evaluable subjects achieved stable disease and six continue to be treated. The most common adverse side effect was neutropenia. No dose-limiting toxicity was reported and the treatment was generally well tolerated. The study enrolled 12 subjects and was designed to evaluate the safety of Pivanex in combination with docetaxel, the standard chemotherapy treatment. Results were reported this week at the 10th World Conference on Lung Cancer in Vancouver.

March 24, 2003

Isis Pharmaceuticals and Lilly reported negative results from a pivotal phase III trial investigating Affinitak, an antisense drug for the treatment of non-small cell lung cancer. Results showed no difference was observed in the primary endpoint, overall survival between the two groups. Subjects receiving Affinitak experienced a median survival of 10 months, compared to 9.7 months for subjects receiving chemotherapy alone. There were no increases in severe toxicities or toxicity related deaths in subjects receiving Affinitak, compared to those receiving chemotherapy alone. However, subjects in the study receiving Affinitak had a higher rate of moderate thrombocytopenia, nausea and vomiting. The trial enrolled 616 chemotherapy naïve subjects with stage IIIb or stage IV non-small cell lung cancer.

January 21, 2003

ImmunoGen reported results of a phase I dose-escalation study of HuC242-DM1/SB-408075 (cantuzumab mertansine) in subjects with refractory cancer that expresses the CanAg antigen. Dosing was increased in each new cohort of subjects until dose-limiting toxicity was demonstrated. Based on the results, the recommended dose for cantuzumab mertansine is 235 mg/m2 when administered once every three weeks. In addition, one subject with colon cancer exhibited DM1 localization at the tumor site 24 hours after administration of the drug. Furthermore, this subject had a reduction in lung metastases after two and four courses of cantuzumab mertansine

Introgen reported positive results from a phase II trial investigating Advexin (p53 therapy) for the treatment of non-small cell lung cancer. Results showed that approximately 60% of subjects' primary tumors regressed or disappeared, as assessed by both biopsies and by CT scans three months after treatment. Administration of the drug did not appear to increase the side effect caused by radiation treatment. The study enrolled subjects with non-metastatic non-small cell lung cancer who were ineligible to receive alternative treatments. Advexin was administered via injection into tumors at a range of doses over one month.

Rational Therapeutics reported positive results from two phase II trials investigating gemcitabine with cisplatin as a combination therapy in the treatment of relapsed ovarian cancer. In the first study, results showed that the combination therapy achieved a 70% response rate, with more than 20% of subjects achieving complete remission. Subjects who demonstrated the most tumor response also showed the most sensitivity to the drug in ex-vivo laboratory assays. Out of 27 subjects, there were 26% (7) complete and 44% (12) partial responses. Subjects received cisplatin (30 mg/m2) plus gemcitabine (600-750 mg/m2) intravenously. Seventeen subjects underwent ex vivo analyses for correlation with clinical response. The second study enrolled 36 platinum and paclitaxel resistant subjects. Of the 15 subjects that responded, 11 were partial clinical responses and 4 were complete clinical responses. Gemcitabine (750 mg/m2) was administered intravenously over 30 min followed by cisplatin (30 mg/m2).

July 8, 2002

Positive follow-up data was obtained from a phase I/II trial of Cell Genesys' Gvax lung cancer vaccine. The multicenter trial, which evaluated vaccine made directly from subject tumor biopsies, included non-small cell lung cancer (NSCLC) subjects with either advanced heavily pretreated disease or early stage disease with high risk of relapse after surgery. Data for 33 advanced disease subjects showed a median survival of 8.0 months, compared to the reported 5.7-7.0 months for docetaxel, the approved second-line chemotherapy for such patients, or 4.6 months for best supportive care. Two of the three subjects with advanced disease who achieved a durable complete response had a lung cancer subtype referred to as bronchoalveolar carcinoma (BAC); this diagnosis was found to be the only identifiable predictor of increased survival in the advanced subject group. Based on the study data, the company plans to focus the next trials of the vaccine on BAC, as opposed to initiating a trial for all NSCLC types.

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