Clinical Trials Resource Center

Anemia; Non-Small-Cell Lung Cancer

November 16, 2015

Merck has reported results of a randomized, pivotal phase II/III study comparing two doses of Keytruda (the FDA-approved 2mg/kg dose and a higher, investigational 10mg/kg dose, each given every three weeks) to docetaxel, a commonly used chemotherapy, for advanced non-small-cell lung cancer (NSCLC). KEYNOTE-010 is a global, open-label study in 1,034 patients. A topline analysis revealed that treatment with Keytruda was associated with longer overall survival (OS) compared with docetaxel treatment. That result was true for both the approved and the investigational dose of Keytruda, which showed similar efficacy. It was also true in both the first set of patients analyzed—those with a tumor proportion scores (TPS) of 50% or greater and for all enrolled patients, all of whom had a TPS of 1% or greater. Treatment with Keytruda, at both doses, also provided superior progression-free survival (PFS) v. that achieved following treatment with docetaxel in patients whose tumors had TPS values equal to or greater than 50%. For PFS, Keytruda treatment was numerically but not statistically superior to docetaxel in the all PD-L1 positive group, again at both doses. The safety profile of Keytruda in that trial was consistent with that observed in previously reported studies in patients with advanced NSCLC.

November 2, 2015

Immunomedics has reported results of a phase III trial of sacituzumab govitecan for metastatic triple-negative breast (TNBC), small-cell (SCLC) and non-small-cell lung (NSCLC) cancers. At the time of analysis, 56 enrolled patients had received sacituzumab govitecan at the optimal dose of 10mg/kg given on days one and eight of a three-week cycle. Treatment response was available for 52 patients. The objective response rate was 29% (15/52), with two confirmed complete responses. The interim median progression-free survival (PFS), a measure of time patients are living without their cancer progressing, was seven months. Forty-six percent of these TNBC patients had experienced a PFS event. Overall survival (OS) data were too early to report because 86% of patients are still alive. For metastatic lung cancers, 33 patients with NSCLC were enrolled to receive sacituzumab govitecan at the or 10mg/kg dose level. Among 29 patients assessable, an objective response rate of 28% (8/29) was observed, including patients with both squamous cell and adenocarcinoma NSCLC types. For the 25 patients at the 10mg/kg dose, the interim median PFS was 3.8 months, with 48% of patients in this dose group having experienced a PFS event. In SCLC, of the 27 patients enrolled at doses of 8mg/kg and 10mg/kg, 25 were assessable for response. Six patients achieved a partial response (objective response rate=24%). Interim median PFS for the 12 patients at the 10mg/kg dose level was 3.6 months and 83% of patients had experienced a PFS event. Since 96% of NSCLC patients and 100% of SCLC patients were still alive at the time of analysis, OS data at the optimal dose of 10mg/kg are too early to report. Sacituzumab govitecan has received Fast Track designation from the FDA for the treatment of patients with TNBC, SCLC and NSCLC, and also has been designated an orphan drug for SCLC or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the E.U.

March 2, 2015

Immunomedics reported results of a study of sacituzumab govitecan for treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A total of 44 heavily-pretreated patients with relapsed or refractory lung cancer have been enrolled into this multicenter study. At the time of analysis, 16 patients with SCLC and 18 with NSCLC were evaluated by computed tomography for response and time-to-progression (TTP). Despite the late-stage setting, TTP for most patients was longer with sacituzumab govitecan than the duration of their previous lung cancer therapy. 33% of patients with SCLC and 31% with NSCLC had their tumor reduced in size by 30% or more. Sacituzumab govitecan controlled the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed. Sacituzumab govitecan continues to produce an acceptable safety profile in heavily-pretreated patients, with neutropenia (24% grades three and four combined) as the major toxicity. Diarrhea, the typical side effect of irinotecan treatment, was minimal at 3% grade three. More importantly, repeated efficacious doses of the ADC can be given to patients over months without evoking any interfering immune response.

February 9, 2015

Boehringer Ingelheim released results of two phase III trials of afatinib compared to standard chemotherapy for epidermal growth factor receptor (EGFR) mutation-positive patients with metastatic non-small cell lung cancer (NSCLC). In the two individual phase III studies, treatment-naïve patients with stage IIIB/IV lung adenocarcinoma and confirmed EGFR mutations in the tumor were enrolled in LUX-Lung 3 (n=345; recruited globally) and LUX-Lung 6 (n=364; recruited in China, Korea and Thailand). Patients were randomized (2:1) to receive oral afatinib (40mg/day) or up to six cycles of intravenous pemetrexed/cisplatin (LUXLung 3) or gemcitabine/cisplatin (LUX-Lung 6) at standard doses. Stratification factors included EGFR mutation type (Del19 v. L858R v. other “uncommon” mutations) and race (Asian v. non-Asian; LUX-Lung 3 only). Results from both trials showed similar OS in the afatinib and chemotherapy arms in the overall NSCLC EGFR mutation-positive population (LUX-Lung 3: median OS 28.2 to 28.2 months, HR 0.88; p=0.39); (LUX-Lung 6: median OS 23.1 to 23.5 months, HR 0.93; p=0.61). There was a survival benefit of more than a year (LUX-Lung 3: median OS 33.3 to 21.1 months; HR 0.54; p=0.0015); (LUX-Lung 6: median OS 31.4 to 18.4 months; HR 0.64; p=0.0229).

November 10, 2014

Bristol-Myers Squibb reported results from a phase II, single-arm, open-label study of Opdivo (nivolumab) in patients with advanced squamous cell non-small cell lung cancer (NSCLC) who have progressed after at least two prior systemic treatments with 65% receiving three or more prior therapies (n=117). The trial, Checkmate -063, was designed to assess advanced squamous cell NSCLC patients who progressed after both platinum-based therapy and at least one additional systemic therapy, with an ECOG Performance Status of zero or one. Subjects were treated with Opdivo as a single agent 3mg/kg by intravenous infusion every two weeks until disease progression or treatment discontinuation (n=117). With approximately 11 months of minimum follow up, the objective response rate (ORR, the study’s primary endpoint) was 15% (95% CI = 8.7, 22.2) as assessed by an independent review committee (IRC) using RECIST 1.1 criteria, and the median duration of response was not reached. The estimated one-year survival rate was 41% (95% CI = 31.6, 49.7) and median overall survival (mOS) was 8.2 months (95% CI = 6.05, 10.91). Grade 3-4 drug-related adverse events (AEs) were reported in 17.1% of patients. The most common Grade 3-4 AEs (greater than or equal to 2%) were fatigue (4.3%), pneumonitis (3.4%) and diarrhea (2.6%). Discontinuations due to drug-related AEs of any grade occurred in 12% of patients, and there were two drug-related deaths in patients with multiple co-morbidities and in the setting of progressive disease.

October 20, 2014

Puma Biotechnology issued results of a phase II trial of PB272 (neratinib) for the treatment of non-small cell lung cancer (NSCLC) with HER2 mutations. In the trial, patients with confirmed stage IIIB or stage IV NSCLC with documented somatic HER2 mutations were randomized to receive either oral neratinib monotherapy, 240mg per day, or the combination of oral neratinib, 240mg daily, with intravenous temsirolimus administered at a dose of 8mg per week. A total of 27 patients completed the first stage of the trial; 13 of these patients received neratinib monotherapy and 14 of these patients received the combination of neratinib plus temsirolimus. Results showed that of the 13 patients who received neratinib monotherapy, no patient experienced a partial response, seven (54%) patients achieved stable disease and four (31%) patients achieved clinical benefit (defined as a partial response or stable disease for 12 or more weeks). For the 14 patients who received the combination of neratinib plus temsirolimus, three (21%) patients experienced a partial response, 11 (79%) patients experienced stable disease and nine (64%) patients achieved clinical benefit. The median progression free survival of the neratinib monotherapy arm was 2.9 months and the median progression free survival of the arm that received neratinib plus temsirolimus was four months. Patients continue to be enrolled in the arm of the trial that is receiving the combination of neratinib plus temsirolimus.

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.

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.

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.

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