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Non-Hodgkin's Lymphoma

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October 1, 2012

Cell Therapeutics reported results from a phase I trial of pacritinib (SB1518) for the treatment of relapsed/refractory lymphoma. This multi-arm, dose-finding study enrolled 34 patients with relapsed or refractory Hodgkin’s or non-Hodgkin’s lymphoma of any type except Burkitt’s or CNS lymphoma. Subjects received pacritinib ranging from 100mg to 600mg daily. Data showed the maximum dose was not met. Pacritinib inhibited JAK2 signaling at all dosing levels and FLT-3 inhibition were seen in most patients. Seventeen of the 34 patients (50%) had measurable decreases in target tumor measurements ranging from 4% to 70% shrinkage. Partial remissions were noted in three patients (mantle cell and indolent lymphoma), while 15 patients had stable disease. Median progression-free and overall survival was 120 and 130 days, respectively. Pacritinib was well tolerated. The most frequent adverse events were gastrointestinal. Based on these data, Cell Therapeutics will continue with efficacy studies of JAK/STAT pathway inhibitors, either alone or in combination regimens.

February 8, 2010

Keryx reported positive results from a phase II trial of perifosine for advanced Waldenstrom's Macroglobulinemia. This open label, single agent trial enrolled 37 subjects with relapsed or refractory disease. The subjects received 150 mg perifosine orally every night for six back to back 28 day cycles. Stable or responding subjects were allowed to continue therapy until progression. Of the 37 subjects, four achieved a partial response (11%), nine achieved a minimal response (24%), and 20 showed stable disease (54%). Overall, 89% of subjects were reported to have stable disease or better, while 11% demonstrated progression. The median progression-free survival was 12.6 months, with a median overall survival of 26 months. Perifosine was generally well-tolerated.

June 15, 2009

Novartis released positive results from a phase II trial of everolimus (Afinitor) for the treatment of non-Hodgkins lymphoma and Hodgkins disease. This open-label, single-arm study enrolled 145 subjects with relapsed/refractory aggressive or indolent NHL or Hodgkin's disease whose disease progressed despite prior treatment. The subjects received everolimus 10 mg daily and were evaluated monthly. Dose reductions to 5 mg daily and 5 mg every other day were permitted. The primary endpoint was overall response rate (ORR). Results showed that 33% of subjects treated with everolimus experienced a 50% or greater reduction in tumor size. This 33% overall response rate (ORR) is defined as complete or partial tumor shrinkage. The median time to disease progression for all subjects was 4.3 months and of the 48 responders the median duration of response was 6.8 months. Nineteen of the 48 responders remained progression free at six months Anticancer activity was observed across multiple types of lymphoma, including T-cell non-Hodgkin's lymphoma (63% ORR), Hodgkin's disease (53% ORR), follicular lymphoma (50% ORR), mantle cell lymphoma (32% ORR), DLBCL (30% ORR).

February 2, 2009

Cell Therapeutics released positive results from a phase III trial of pixantrone for the treatment of non-Hodgkin's lymphoma. This single-agent trial enrolled 140 subjects with relapsed, aggressive non-Hodgkin's lymphoma who had received two or more prior therapies and who were sensitive to treatment with anthracyclines. The subjects were randomized to receive either pixantrone or another single-agent drug currently used in this patient population and selected by the physician. The primary endpoints were complete remission or unconfirmed complete remission rate, overall survival and progression-free survival. The pixantrone treatment arm achieved a significantly higher rate of confirmed and unconfirmed complete remissions compared to the standard chemotherapy arms (20% versus 5.7%; p≡0.02). No subjects in the standard chemotherapy arm achieved a confirmed complete remission. Pixantrone treatment also significantly increased the overall response rate compared to standard chemotherapy (37.1% versus 14.3%; p≡0.003). In addition, a pixantrone led to a statistically significant improvement in median progression-free survival compared to the other single-agent chemotherapeutic agents (4.7 months versus 2.6 months, p<0.01). Based on the results. Cell Therapeutics plans to begin submission of a rolling NDA and request priority review to treat relapsed aggressive NHL in the first quarter of 2009.

November 17, 2008

Cell Therapeutics released positive results from a phase III trial of pixantrone for the treatment of non-Hodgkin's lymphoma (NHL). This international, single agent, blinded trial, dubbed EXTEND, enrolled 140 subjects with relapsed, aggressive NHL who had received two or more prior therapies for their disease and who were sensitive to treatment with anthracyclines. The subjects were randomized to receive either pixantrone or another single-agent drug currently used for this patient population and selected by the physician. The trial was designed to examine the complete response or unconfirmed complete response rate and overall survival. The subjects who were treated with pixantrone achieved a higher rate of confirmed and unconfirmed complete remissions compared to those treated with standard chemotherapy (20.0% versus 5.7%; p≡0.02). No subjects in the standard chemotherapy arm achieved a confirmed complete remission compared to 11% of subjects in the pixantrone arm. In addition, pixantrone treatment also significantly increased the overall response rate compared to standard chemotherapy (37.1% versus 14.3%; p ≡ 0.003).

October 20, 2008

Cell Therapeutics released positive results from a phase III trial of Zevalin for the treatment of follicular non-Hodgkins lymphoma. This multinational, randomized study, dubbed FIT (First-line Indolent Trial), enrolled 414 subjects with newly diagnosed CD20-positive follicular non-Hodgkins lymphoma who had achieved a partial response or a complete response after receiving a variety of first-line chemotherapy regimens. The FIT trial demonstrated that when used as a first-line consolidation therapy, Zevalin significantly improved the median progression-free survival time from 13.3 months (control arm) to 36.5 months (Zevalin arm) (p<0.0001). This advantage was observed regardless of whether subjects were in partial remission (29.3 versus 6.2 months without Zevalin: p<0.0001) or complete remission (53.9 versus 29.5 months p=0.0154). In addition, 77% of subjects who had achieved only a partial remission after induction therapy were converted to complete remission / complete remission unconfirmed following Zevalin consolidation therapy. Based on the results, a sBLA was submitted to the FDA for use of Zevalin in first-line consolidation therapy.

June 9, 2008

Keryx issued positive interim results from a phase II trial of KRX-0401 for the treatment of relapsed/refractory Waldenstroms macroglobulinemia (WM). This study enrolled 37 subjects, most of who had been previously treated with at least one course of therapy on rituximab. The subjects received 150 mg of perifosine daily in a 28 day cycle for at least six cycles. Partial response, defined as a 50 percent reduction in Immunoglobulin M, was observed in 5% of the subjects and minimal response, defined as a 25 percent reduction in Immunoglobulin M, was observed in 28% of the subjects. This resulted in an overall response rate of 33%. An additional 61% of the subjects reached stable disease. Treatment was well tolerated. The median time to progression has not been reached. Eleven subjects are currently receiving treatment.

April 28, 2008

Medarex reported positive results from a phase I/II trial of MDX-060 for the treatment of relapsed or refractory CD30- positive lymphomas. This dose-escalation study enrolled seventy-two subjects who received weekly doses of MDX-060 (0.1, 1, 4, 10 or 15 mg/kg) for four weeks. Of the thirty-three subjects treated at the two highest doses of MDX-060, disease control was observed in 51% (three complete responses, fourteen stable disease). Median progression- free survival was 3.7 months and 39% of subjects showed no evidence of disease progression four months post-treatment. Of the thirty-nine subjects treated at the three lowest doses of MDX-060, disease control was observed in 33% (one complete response, two partial responses, ten stable disease). Median progression-free survival was less than two months and 18% of subjects showed no evidence of disease progression four months post-treatment. MDX-060 treatment was well-tolerated with no clinically meaningful infusion reactions. A phase II trial of MDX-060 is currently underway.

January 14, 2008

Genitope reported negative results from a phase III trial of MyVax for the treatment of previously untreated follicular B-cell non-Hodgkins lymphoma (fNHL). The subjects enrolled in this double-blind, randomized, controlled clinical trial first received chemotherapy to reduce their tumor burden, followed by a 6-month rest period. Subjects who maintained at least a partial response through the rest period were then randomized to the MyVax personalized immunotherapy or control arm in a 2:1 ratio. Subjects who received MyVax personalized immunotherapy received a patient- and tumor-specific idiotype protein conjugated to a foreign carrier protein called keyhole-limpet hemocyanin (KLH). Subjects in the control arm received a non-specific immunotherapy consisting only of KLH. Subjects in both arms received granulocyte macrophage-colony stimulating factor (GM-CSF) as an immunologic adjuvant at each immunization. Although treatment was determined to be safe and well tolerated, the trial did not meet its primary endpoint. In the primary analysis, there was no statistically significant difference in the progression-free survival (PFS) of subjects receiving MyVax compared to the control arm. Analysis of a pre-specified endpoint in the MyVax arm showed a highly statistically significant difference in PFS between subjects who mounted a positive immune response to the tumor-specific target and those who did not. Based on the results, Genitope plans to meet with the FDA to determine the path forward for MyVax personalized immunotherapy.

October 29, 2007

Cephalon reported positive results from a phase III trial of Treanda for the treatment of non-Hodgkins lymphoma (NHL). This multicenter, single-arm study, conducted under a SPA from the FDA, enrolled 100 subjects with relapsed, rituximab-refractory NHL who were no longer responsive to treatment with rituximab. The primary endpoints, overall response rate and median duration of response, were both achieved. The overall response rate, including complete, unconfirmed complete or partial response, was reached by 75% (p<0.0001) and the median duration of response was 40 weeks (9.2 months). Treatment was determined to be safe and well tolerated. Based on the results, Cephalon plans to file a sNDA with the FDA in Q4 of 2007.

EntreMed issued positive results from a phase II trial of Panzem for the treatment of ovarian cancer. This open label trial enrolled 18 women with platinum refractory epithelial ovarian cancer who received Panzem administered as a single agent. One subject had confirmed partial response of their CA- 125, a tumor bio-marker. Five of the eighteen subjects achieved stable disease lasting greater than three months. Treatment was well tolerated, with no reports of significant neuropathy, myelosuppression or thromboembolic side effects. Two subjects remain in the study at this time. Based on the results, EntreMed plans to advance the development of Panzem for this indication.

September 10, 2007

Kiadis released positive results from a phase II trial of Reviroc for the treatment of hematological cancers. This non-randomized open label study enrolled 25 subjects with end-stage Non-Hodgkin's lymphoma in Canada. All subjects underwent an autologous graft in bone marrow transplantation using Reviric or a control. The objective of the study was to determine the safety of the Reviroc treatment and its ability to eliminate cancer cells from a contaminated graft. Reviroc was able to eliminate cancer cells from a contaminated graft with out negatively impacting the graft itself. In addition, the Reviroc group had an 80% chance of survival at three years post-transplantation while the control group had a 55% chance of survival. Based on the results, Kiadis is preparing to commence phase III trials.

July 30, 2007

Genzyme reported positive results from a phase III trial of Mozobil as an agent for increasing the number of hematopoietic stem cells collected for a transplant. This randomized, double-blind, placebo-controlled trial enrolled 298 subjects undergoing a hematopoietic stem cell transplant (HSCT) for non-Hodgkin's lymphoma, in the US and Canada. The trial was designed to compare the hematopoietic stem cell yield from subjects treated with Mozobil in combination with granulocyte-colony stimulating factor (G-CSF, standard of care) to subjects treated with G-CSF in combination with placebo. The primary efficacy endpoint was achieved, with 59% of the subjects in the Mozobil arm reaching the target threshold for collection of at least 5 million CD34+cells/kg from the peripheral blood with four or fewer days of apheresis sessions, compared with 20% in the placebo arm (p=0.0001). The secondary endpoint also reached statistical significance, with nearly 87% of the subjects in the Mozobil arm minimum level of stem cells generally associated with a successful transplant (2 million CD34+cells/kg) in four or fewer days of apheresis sessions, compared to 47% in the placebo arm (p<0.0001). Genzyme plans to file for US and European approval for lymphoma in the first half of 2008.

July 16, 2007

Cell Therapeutics issued positive interim results from a phase II/III trial of pixantrone for the treatment of non-Hodgkin's lymphoma (NHL). This randomized trial, dubbed RAPID (Replacing Adriamycin with Pixantrone to Improve Safety in NHL Disease) enrolled 280 subjects. The subjects were randomized to either standard of care CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) or a regimen replacing doxorubicin with pixantrone, CPOP-R (cyclophosphamide, pixantrone, vincristine, prednisone, and rituximab), for six cycles. Subjects were evaluated every two cycles and every two months following therapy. Subjects in both arms reached objective anti-tumor response, including complete and partial response. In the subjects receiving pixantrone, a three-fold reduction in the incidence of severe heart damage (LVEF decline >15 percent) was observed as well as a significant reduction in febrile neutropenia. A phase III trial design is currently under review by the FDA.

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 19, 2007

Bayer and Onyx announced positive results from a phase III trial of Nexavar for the treatment of hepatocellular carcinoma. This double-blind, randomized, placebo-controlled trial, dubbed SHARP (Sorafenib HCC Assessment Randomized Protocol), enrolled 602 subjects with primary liver cancer who had not undergone prior systemic therapy. Subjects received 400 mg of oral Nexavar twice daily or matching placebo. Treatment was well tolerated with no difference in adverse events between the two treatment arms. The trial's primary endpoint was met, with the Nexavar arm resulting in superior overall survival when compared to the placebo arm. Based on these results, Bayer and Onyx stopped the trial to allow all of the subject's access to Nexavar. They plan to move forward with filing for FDA approval.

Favrille reported positive long-term results from a phase II trial of Favld for the treatment of non-Hodgkin's lymphoma (NHL). This trial enrolled 15 subjects who received Favld after high dose therapy and autologous stem cell transplantation. The first of five monthly injections of Favld was administered three months following transplantation. The trial was designed to evaluate the ability of treatment to induce humoral and cell-mediated immune responses, and to induce or maintain complete remission. Treatment was well tolerated. Data revealed that the majority of the subjects developed a rapid and tumor-specific immune response. In addition, at 61 months post-transplant, nine of the subjects remained in complete transmission. Favld is currently undergoing a second phase III trial with results expected by the end of 2007.

July 17, 2006

Favrille reported positive interim results of a phase II trial of FavId for the treatment of indolent B-cell non-Hodgkin's lymphoma (NHL) in the Journal of Clinical Oncology. Trial data yielded evidence of efficacy: median time to disease progression was 13.5 months, and median duration of response had not been reached through 19.4 months (range 10.4-27.2+ months). Median time to onset of response was 5.9 months. This multi-center open-label single-agent study evaluated 31 patients, who single SC injections of 1 mg FavId on day 1 plus 250 mcg granulocyte-macrophage colony-stimulating factor on days 1 to 4, monthly for 6 months, with additional booster cycles administered until evidence of disease progression.

May 22, 2006

Cell Therapeutics reported preliminary results of a phase I/II trial of pixantrone for the treatment of non-Hodgkin's lymphoma (NHL) at the Rodman & Renshaw 3rd Annual Global Healthcare Conference in Monte Carlo, Monaco. Trial data yielded a 95% overall objective response rate for patients treated with a combination regimen including pixantrone, dubbed FPD-R (fludarabine, pixantrone, dexamethasone, rituximab). 77% of patients achieved complete response (confirmed or unconfirmed), and 18% achieved partial disease response. Overall 2-year survival was 85%, and median treatment-failure free survival duration was 25 months. This open-label study enrolled 22 patients with relapsed indolent NHL, who received cycles of the FPD-R regimen every 28 days.

March 27, 2006

Cell Therapeutics announced positive results of a phase I/II trial of pixantrone for the treatment of non-Hodgkin's lymphoma at the 2006 Invest Northwest conference. Trial data indicated that use of the drug in place of doxorubicin in a modified regimen of CHOP chemotherapy (cyclophosphamide, vincristine, prednisone and doxorubicin), dubbed CPOP, was efficacious in treating the disease: in the phase I portion of the study 41% (n=14/34) of patients experienced complete disease response and an overall response rate of 71% (n=24/34); in the phase II portion, response rates were 43% (n=13/30) and 77% (n=23/30), respectively. Adverse events were largely hematological in nature, including a 60%-75% rate of grade 4 neutropenia, and a 23% rate of febrile neutropenia. This open-label study enrolled a total of 64 subjects, who received treatment with the CPOP chemotherapy regimen with escalating doses of pixantrone from 80 mg/m2 to 180 mg/m2.

January 16, 2006

Biovest, a subsidiary of Accentia Biopharmaceuticals, announced follow-up results of a phase II trial of their BiovaxID personalized vaccine for the treatment of follicular non-Hodgkin's lymphoma. After a median follow-up of 9.2 years, 45% of patients had maintained continuous first remission following treatment. Median disease free survival was 96.5 months, and overall survival rate was 95%; these values compares favorably to historical values for other therapies. This single-arm study enrolled patients achieving first clinical remission following chemotherapy, who received multiple subcutaneous administrations of the drug.

December 5, 2005

Genmab announced expanded positive results of a phase I/II trial of their investigational monoclonal antibody HuMax-CD20 for the treatment of non-Hodgkin's lymphoma. Overall objective response rate was 43%, including 5 complete responses (CR), 2 unconfirmed complete responses (CRu), and 9 partial responses (PR). Dose-response analysis indicated the highest response rates among the lowest (300 mg, 63%) and highest (1000 mg, 60%) dose groups. Also, among patients who had previously responded to treatment with rituximab (n=14), objective response rate was 64% (n=9; 3 CR, 1 CRu, 5 PR). This open-label dose-escalation study enrolled 37 evaluable patients, who received one of four doses of the drug (300, 500, 700 or 1000 mg) once weekly for four weeks, with a 12 month observational follow-up.

November 14, 2005

Cell Therapeutics reported positive results of a phase III trial, dubbed PIX302, investigating the addition of pixantrone to an approved regimen of rituximab for the treatment of indolent non-Hodgkin's lymphoma (NHL). These results were presented at the CIBC World Markets 16th Annual Healthcare Conference. Trial data met their primary efficacy endpoint, with the combination significantly prolonging time to disease progression to 13.2 months, compared to 8.1 months for rituximab alone (p<0.001). One-year and two-year progression free survival rates were 66% and 44%, respectively, vs. 0% for both values for the single therapy (p<0.001 and p<0.003). Study data also met secondary endpoints, with 75% of subjects experiencing major tumor response (50% or greater tumor shrinkage), including a 35% complete response rate, compared to 33% and 11% (p=0.02). Treatment related adverse events for pixantrone were generally mild to moderate (grade 1-2), with the exception of 2 cases of severe (grade 4) neutropenia. This multi-center randomized study enrolled 38 patients with refractory indolent NHL, who received either combination treatment (n=20) with pixantrone (90 mg/m2 given on days 1 and 8 every 21 days) plus rituximab (375 mg/m2 given on days 1, 8, 22, and 29), or monotherapy (n=18) with rituximab alone.

October 31, 2005

Procyon BioPharma has issued positive interim results of a dose-finding study of PCK3145, for the treatment of prostate cancer. Trial results have demonstrated a positive overall tolerability profile, with no serious adverse events reported to date. Preliminary bioactivity data yielded reductions in plasma levels of the metastatic enzyme matrix metalloproteinase-9 (MMP-9). Efficacy results from one patient demonstrated stable levels of prostate-specific antigen and tumor growth scans through 4 treatment cycles. This ongoing, open-label study planned to enroll a total of 20 subjects, who were randomized 1:1 to receive either 7.5mg/m2 twice weekly or 15mg/m2 once weekly for 4 weeks, followed by 2 weeks off treatment. The company announced that 4 subjects remained to be enrolled, and successful completion of this trial was to inform the optimum dose regimen for upcoming North American phase II trials.

Roche has reported positive results of a phase III trial of MabThera (rituximab) for the treatment of relapsed indolent non-Hodgkin's lymphoma (NHL). The drug is currently approved in both the US (as Rituxan) and EU for the acute treatment of NHL. Trial data indicated that continued administration of the drug as a single-agent maintenance treatment for NHL yielded significant improvements in 2-year progression free survival rates following initial treatment with MabThera and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. This open- label extension study enrolled 485 subjects from the initial acute-treatment study, who received MabThera via infusion once every 3 months or no additional treatment. Based on these results, this extension study was terminated to allow all subjects to receive the drug; final data were to be presented in December 2005 at the annual meeting of the American Society of Hematology.

February 7, 2005

Millennium Pharmaceuticals and Johnson & Johnson Pharmaceutical R&D reported results of a pair of phase II studies investigating the approved drug Velcade (bortezomib) for the treatment of non-Hodgkin’s lymphoma (NHL). The first study found indications of efficacy, with objective remission noted in 7 of 9 patients with follicular lymphoma (1 durable CR, 1 unconfirmed CR, 5 PR), 5 major remissions and 4 stable disease states in the 10 patients with mantle cell lymphoma, and 2 of 2 patients with nodal marginal zone lymphoma responding. Total response rate was 58%. Adverse events were generally manageable and anticipated, including thrombocytopenia, lymphopenia, neuropathy, hypoatremia, hypokalemia, and prothrombin time. The second study yielded similar findings, with 12 of 29 patients with mantle cell lymphoma (6 CR, 6 PR) and 4 of 21 patients with B-cell lymphoma experiencing objective response. Adverse events were also similar and manageable, and included thrombocytopenia, gastrointestinal events, fatigue, neutropenia, peripheral neuropathy, dizziness, and myalgia. Both studies were open-label trials which treated patients with single agent Velcade (1.5 mg/m2) twice weekly for 2 weeks, followed by a week dose free; the first enrolled 24 evaluable patients with NHL (follicular, mantle cell, small lymphocytic and marginal zone) refractory to no more than 3 prior therapies with no limit on total number of treatment cycles; the second study enrolled 40 patients with NHL (mantle cell or B-cell) refractory to any number of prior regimens for a maximum of 6 cycles.

Sanofi-Aventis announced positive preliminary results from a clinical trial of their approved drug Eloxatin (oxaliplatin), for the treatment of colorectal cancer. The trial, dubbed “TREE-2,” assessed the drug as a first-line treatment for the disease in combination with Genentech’s Avastin (bevacizumab). The trial found that the addition of bevacizumab to chemotherapy regimens involving Eloxatin and one of three fluoropyrimidine treatments (FOLFOX, bFOL, or CAPEOX), produced no unexpected toxicities, and preliminary evidence indicated improved efficacy, especially with the FOLFOX and CAPEOX regimens. This randomized, multi-center study enrolled 213 subjects with treatment naïve metastatic colorectal cancer, who received one of the three chemotherapy regimens in combination with bevacizumab. The company announced that they expected to present full results of this trial in May 2005 at the 41st Annual Meeting of the American Society of Clinical Oncology.

September 27, 2004

Maxim Pharmaceuticals has issued negative results of a phase III trial of their investigational immunosupportive drug Ceplene, for the treatment of malignant melanoma. The trial failed to meet its primary endpoint, with no significant increase in patient survival among subjects receiving Ceplene plus Interleukin-2 (IL-2), versus subjects receiving IL-2 alone. This trial was conducted as an extension of a previous trial, which found a significant improvement in patient survival at one, two and three years among a subgroup of its trial population, advanced malignant melanoma patients with liver metastases; results among the entire trial population of this earlier trial were non-significant. This multicenter, randomized, approved-therapy controlled study enrolled 235 subjects across 35 sites in North America and Europe, all of whom had advanced malignant melanoma with liver metastases. Maxim announced that they intended to continue the development of Ceplene for other cancer indications, and announced that data analysis for this trial was ongoing.

OSI, Genentech, and Roche have announced the results of a phase III trial of Tarceva, their HER1/EGFR tyrosine kinase inhibitor, for the treatment of pancreatic cancer. Data demonstrated that a combination of Tarceva plus gemcitabine chemotherapy improved outcomes versus gemcitabine plus placebo, with a significant improvement in overall survival of 23.5%. In addition, Tarceva-plus-gemcitabine produced significant improvements in risk of death, median survival time, percentage of subjects reaching one year survival, and progression free survival time. No significant difference was observed in tumor response. This randomized, double-blind, placebo-controlled study enrolled a total of 569 subjects with advanced metastatic pancreatic cancer at investigative sites worldwide; all subjects received a standard regimen of gemcitabine chemotherapy, plus one of two doses of Tarceva daily or placebo. The companies announced that following final review and publication of trial data, they would be presented to the FDA to determine the next steps for Tarceva’s development in this indication. An NDA for Tarceva is currently under review by the FDA, for second-line monotherapy treatment of advanced non-small cell lung cancer.

Pharmacyclics announced interim results of their phase I trial of Xcytrin for the treatment of non-Hodgkin’s lymphoma. Data from the ongoing study indicate that the addition of Xcytrin to standard therapy (Rituxan-plus-Zevalin) produced no additional safety concerns or adverse effects in any subjects to date. Furthermore, all three subjects treated to date demonstrated complete remission within one month of treatment initiation; one patient experienced remission for nine months, before a localized relapse, and two have experienced continuing remission for two months. Subjects received a single injection of Rituxan and four daily injections of Xcytrin, followed by a second injection of Rituxan coupled with an injection of Zevalin and four more daily treatments with Xcytrin one week later. This open label study plans to enroll a total of 20 treatment-refractory subjects; all three subjects treated to date had failed three previous treatment courses, including Rituxan monotherapy. Pharmacyclics announced their support of ongoing phase I and II trials in a range on cancers.

December 15, 2003

Aton Pharma reported positive results from a phase II trial investigating SAHA, a suberoylanilide hydroxamic acid for the treatment of T-cell lymphomas (TCL). Results showed that out of thirteen subjects with refractory or relapsed TCL unresponsive to conventional therapies treated with SAHA, five achieved partial remissions as measured by Physician Global Assessment, five had stable disease and three progressed on therapy. The most commonly reported side effects were dry mouth, change in taste, decreased appetite, nausea, diarrhea and fatigue. Results were presented at the American Society of Hematology 45th Annual Meeting in San Diego.

SuperGen reported results from two multicenter clinical studies with Nipent (pentostatin for injection), for the treatment of non-hodgkin's lymphoma (NHL). The first was a phase II trial that enrolled 60 subjects with previously treated and untreated NHL at 25 sites across the U.S. Results showed that the objective response rate at day 60 was 59.6%, with 12 complete responses and 19 partial responses. In addition, the objective response rate at day 115 was 50.9% with 17 complete responses and 9 partial responses. Subjects received a combination of Nipent and rituximab. The second study was a multi-center pilot trial that enrolled 26 subjects with previously untreated, Stage III or Stage IV low-grade NHL. Results showed there were nine complete responses (37.5%), eight partial responses (33.3%) and four subjects with stable disease (16.7%) for an overall response rate of 83.3%. Subjects received a combination consisting of Nipent, mitoxantrone, and rituximab. Results were presented at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.

September 2, 2003

Novuspharma reported positive results from a phase II trial investigating Pixantrone (BBR 2778), a DNA intercalator for the treatment of non-Hodgkin’s lymphoma (NHL). Results demonstrated an overall response rate of 30%, with 17% of subjects achieving complete disappearance of tumor following Pixantrone therapy. The most frequently reported side effect was grade four neutropenia, observed in 13 subjects. The open-label, non-randomized, non-comparative study enrolled 33 subjects with relapsed aggressive NHL. Pixantrone was administered at 85 mg/m(2) on day 1, 8 and 15 of a 4-week cycle. The primary endpoints were to evaluate the efficacy of Pixantrone in terms of the overall subject response rate (CR+PR) according to the WHO criteria. The results were published in the August issue of Haematologica, Journal of Haematology.

July 21, 2003

SuperGen reported positive results from a phase II trial investigating Nipent (pentostatin for injection), as part of a combination therapy for the treatment of non-Hodgkin’s lymphoma. Nipent is currently approved as a single-agent treatment for patients with hairy cell leukemia. Results showed the combination therapy demonstrated activity with acceptable toxicity in subjects with relapsed or unresponsive indolent non-Hodgkin's lymphoma (NHL). Data demonstrated that ten subjects achieved a complete response (33%) and eight achieved a partial response (27%) for an objective response rate of 60%. The study enrolled 30 subjects and was led by Massimo Federico of the Centro Oncologico Modenese, Modena, Italy. Each subject received a combination treatment regimen consisting of Nipent, mitoxantrone, prednisone and bleomycin.

June 30, 2003

INEX Pharmaceuticals reported final results from a phase II/III trial investigating Onco TCS, a liposomal encapsulated vincristine for the treatment of relapsed aggressive non-Hodgkin's lymphoma. Results showed the overall response rate was 25%, including seven subjects (6%) whose tumors were completely eliminated and 23 subjects (19%) who achieved a greater than 50% reduction in tumor volume. Data also demonstrated that 31 subject (26%) treated with Onco TCS had their disease stabilized. The median duration of response was approximately three months from first documentation of response as measured by a computed tomography (CT) scan. The study enrolled 119 subjects and was designed to test the treatment as a single-agent therapy. Subjects had previously received on average four other therapies and 72% had treatment resistant disease.

Millennium Pharmaceuticals reported positive results from a pivotally phase II trial investigating Velcade (bortezomib), now approved for the treatment of multiple myeloma. Results demonstrated that a majority of subjects achieved a reduction or stabilization of their disease severity, with some experiencing a complete response. Data showed that 67 subjects (35%) had a complete, partial or minimal response to treatment with Velcade. The overall median survival rate was 16 months and the median duration of response was 12 months. The multi-center study enrolled 202 subjects with relapsed and refractory multiple myeloma who had averaged six prior therapeutic regimens for their cancer. Subjects received 1.3 mg/m2 of Velcade (bortezomib) for Injection for up to 24 weeks. Study results were reported in the New England Journal of Medicine.

June 16, 2003

Dendreon reported additional positive results from a phase III trail investigating Provenge, an investigational therapeutic vaccine for the treatment of metastatic prostate cancer. Results showed that Provenge induced a significant T-cell mediated immune response compared with placebo. Data revealed Provenge treated subjects demonstrated an eight-fold increase in T-cell proliferation compared to placebo treated subjects. The double blind, placebo controlled study enrolled men with androgen independent prostate cancer. Provenge treated men, with a Gleason score of seven or less, developed a median change in T-cell mediated immune response seven-fold greater than those seen men with a Gleason score of eight and higher. No apparent benefit from Provenge therapy was observed among subjects with Gleason scores of eight or higher. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor.

AltaRex reported positive results from a phase III trial investigating OvaRex (oregovamab), a murine monoclonal antibody for the treatment of ovarian cancer. Results showed the time to relapse was 13.3 months with OvaRex compared with 10.3 months with placebo treatment. Subjects with optimal surgical cyto-reduction and no evidence of disease following chemotherapy showed a dramatic clinical benefit as compared to placebo. Subjects with less favorable response to surgery and chemotherapy did not appear to benefit from OvaRex. The randomized, multi-center, placebo-controlled study enrolled 145 subjects following front-line surgery and chemotherapy for stage III/IV ovarian cancer. The side effect profile for OvaRex treatment was similar to placebo.

Genta reported positive preliminary results from a phase II trial investigating Genasense (oblimersen sodium), a BCl-2 protein inhibitor for the treatment of non-Hodgkin’s lymphoma. Results show that across all Genasense treatment groups, 10 of 25 subjects (40%) remained stable without progression during all six treatment cycles. Out of 16 previously treated subjects, one subject (6%) achieved a complete response, and six subjects (38%) achieved stable disease when receiving Genasense alone. During disease progression subjects who were diagnosed and who had not previously received chemotherapy then received a combination of Genasense plus a standard regimen consisting of Rituxan(R), cyclophosphamide, doxorubicin, vincristine, and prednisone. The ongoing study enrolled 37 subjects with mantle cell lymphoma. So far, 25 subjects are evaluable for response; 14 of these patients are still receiving treatment. The study was designed to evaluate the effects of Genasense used without chemotherapy, given every 3-4 weeks.

Spectrum Pharmaceuticals reported positive results from a phase III trial investigating satraplatin, an oral platinum compound for the treatment of prostate cancer. Results demonstrated statistically significant superiority in time to disease progression with satraplatin and a doubling of progression-free survival. The median time to disease progression was 5.2 months for satraplatin versus 2.5 months for the control arm. Data showed a median overall survival time of 15 months for subjects treated in the satraplatin arm versus 12 months for subjects in the control arm. The randomized study 50 subjects with hormone-refractory prostate cancer and evaluated satraplatin plus prednisone versus prednisone alone for use as a first-line chemotherapy treatment. A greater than 50% decline in PSA (prostate-specific antigen) was experienced by 33% (9/27) of subjects in the satraplatin arm versus 9% (2/23) of subjects in the control arm.

SuperGen reported positive results from a phase III trial investigating Orathecin (rubitecan), a topoisomerase I-inhibitor for the treatment of advanced ovarian cancer. Results showed that 7% (13/196) of subjects given Orathecin experienced either a complete or partial tumor response compared with less than 1% (1/211) for subjects receiving an alternative treatment. The median time to disease progression was 57 days for subjects receiving Orathecin, versus 47 days for subjects receiving alternative. The primary study end-point was overall survival, with secondary end-points of tumor response and time to disease progression. Most of subjects in the alternative treatment group received a chemotherapeutic agent such as gemcitabine, 5-FU, mitomycin C, capecitabine, or docetaxel. The randomized, comparative clinical study enrolled 409 subjects with advanced pancreatic cancer.

August 12, 2002

Large Scale Biology Corporation announced favorable safety results of a phase I trial of its personalized therapeutic vaccines for the treatment of non-Hodgkin's lymphoma (NHL). The plant-expressed single-chain NHL vaccines, which were manufactured individually from each subject's specific tumor RNA sequences, were administered six times over a period of six months. 16 subjects received either a low-dose or a high-dose of their personalized vaccine, with or without Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as an adjuvant therapy. Results showed that the personalized vaccines were well tolerated in all subjects, and no serious adverse events were reported.

January 24, 2002

Two-year follow-up data from a phase III trial suggests that Rituxan (rituximab) plus standard CHOP chemotherapy increases event-free survival in subjects with aggressive non-Hodgkin's lymphoma, compared to CHOP chemotherapy alone. Results from the 399-subject trial showed a significant improvement in the primary endpoint of event-free survival, from 37% with CHOP alone to 57% in the Rituxan/CHOP arm, after a median follow-up of two years. Additionally, overall survival increased from 57% in the group treated with CHOP alone to 70% in the Rituxan/CHOP arm. In terms of complete response, the rate for the Rituxan/CHOP combination was 76%, compared to 63% for the CHOP-alone arm. Rituxan is being developed by Genentech, IDEC Pharmaceuticals and Roche.