Bristol-Myers Squibb’s Opdivo (nivolumab) Receives Expanded FDA Approval in Previously-Treated Metastatic Non-Small Cell Lung Cancer (NSCLC), Offering Improved Survival to More Patients

Bristol-Myers Squibb Company (NYSE:BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection, for intravenous use, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR mutation or ALK translocation should have disease progression on appropriate targeted therapy prior to receiving Opdivo. In a Phase 3 trial, CheckMate -057, Opdivodemonstrated superior overall survival (OS) in previously treated metastatic non-squamous NSCLC compared to chemotherapy, with a 27% reduction in the risk of death (hazard ratio: 0.73 [95% CI: 0.60, 0.89; p=0.0015]), based on a prespecified interim analysis. The median OS was 12.2 months in the Opdivo arm (95% CI: 9.7, 15.0) and 9.4 months in the docetaxel arm (95% CI: 8.0, 10.7). This approval expands Opdivo’s indication for previously treated metastatic squamous NSCLC to include the non-squamous patient population. Squamous and non-squamous NSCLC together represent approximately 85% to 90% of lung cancer cases.”

Nivolumab Improves the Proportion of Lung Cancer Patients Alive After More than a Year

“Patients with a type of lung cancer called non-squamous non-small cell lung cancer (non-SQ NSCLC) have limited treatment options and a dismal prognosis once their disease has advanced and initial treatment with platinum-based chemotherapy has failed. Second-line treatment is usually with another chemotherapy drug, such as docetaxel or pemetrexed.

“Recent results have shown that the drug, nivolumab, improves survival for these and now updated results from the CheckMate 057 phase III clinical trial, to be reported at the 2015 European Cancer Congress today (Monday) with simultaneous publication of the study results in the New England Journal of Medicine, show that nivolumab continues to show an overall survival benefit compared to . Among patients randomised to receive nivolumab, significantly more were alive at 12 months compared to those treated with docetaxel – 51% versus 39% respectively – and a difference in survival remains at 18 months – 39% for nivolumab versus 23% for docetaxel.

“This improvement in survival was observed for all patients included in the trial, but nivolumab was more effective in patients whose tumours expressed a protein called programmed death ligand 1 (PD-L1), which plays a role in the immune system’s ability to recognise and attack tumours and has been correlated with response to immune checkpoint inhibitors such as nivolumab.”

TS Expression Could Guide Treatment in Nonsquamous NSCLC

“The combination of pemetrexed and cisplatin was superior to gemcitabine and cisplatin only in those non-squamous non–small-cell lung cancer (NSCLC) patients who were negative for the enzyme thymidylate synthase (TS), suggesting it could be used as a predictive marker to guide treatment.

“Previous research has shown that pemetrexed/cisplatin offers superior survival in nonsquamous NSCLC, while gemcitabine/cisplatin was better in squamous NSCLC. “A plausible mechanism for the histotype-dependent efficacy of pemetrexed-based chemotherapy can be explained by the presence of different levels of TS according to histologic types, with adenocarcinoma of lung cancer exhibiting a lower TS protein expression level than squamous cell carcinoma or neuroendocrine carcinoma,” wrote study authors led by Myung-Ju Ahn, MD, PhD, of Sungkyunkwan University School of Medicine in Seoul.

“TS is involved in de novo DNA synthesis, and inhibiting the enzyme leads to arrested cell proliferation; pemetrexed’s antitumor effects arise from inhibition of TS. The new study’s results were published online ahead of print in the Journal of Clinical Oncology.”

Biothera Presents Additional Data at ASCO on Durability and Characteristics of Response with Imprime PGG in Non-Small Cell Lung Cancer Study

“Biothera’s investigational cancer immunotherapy Imprime PGG in combination with standard platinum-based doublet chemotherapy and the monoclonal antibody bevacizumab achieved rapid and lasting responses in patients with non-squamous non-small cell lung cancer (NSCLC). Tumor reduction was observed regardless of tumor burden (up to > 30 cm) or location of lesions at baseline (including lung, lymph nodes, adrenals, liver). These findings were presented yesterday during a poster session at the annual meeting of the American Society of Clinical Oncology (abstract #3070).

“During Biothera’s randomized clinical study in non-squamous NSCLC, patients received four to six cycles of Imprime PGG in combination with bevacizumab and carboplatin/ paclitaxel chemotherapy. These treatment cycles were followed by a maintenance therapy phase consisting of bevacizumab with or without Imprime PGG.

“Overall, the objective response rate was 60.4% with Imprime PGG versus 43.5% in the control group. Time to response was short (12 weeks vs. > 16 weeks), and responses were durable with Imprime PGG (10.3 months vs. 5.6 months). In the maintenance phase, further meaningful tumor reductions were observed in 20% of patients in the Imprime PGG group, but none in the control group. These findings were associated with numerical increases in overall survival: at the 1-year mark (following treatment start) 62.8% of patients on Imprime PGG remained alive, compared with 42.7% of patients in the control group.”

Bristol's Opdivo Reduces Risk of Death from Common Lung Cancer

“Chicago May 29 Bristol-Myers Squibb Co’s drug, Opdivo, improved survival for patients with the most common form of lung cancer, nearly doubling survival for those with high levels of a specific protein in their tumors compared with chemotherapy, according to clinical trial results presented on Friday.

“The trial found that Opdivo, part of a new class of drugs that harness the immune system to fight cancer, reduced by 27 percent the risk of death from advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy. The benefit reached 60 percent for patients with the highest levels of the PD-L1 protein.

“The Bristol drug was approved by U.S. regulators in December to treat advanced melanoma and competes with Keytruda from Merck & Co Inc. Investors have been keeping a close eye on Opdivo’s performance in lung cancer, the most common form of the disease worldwide, and a far larger market. Opdivo was cleared in March to treat the less-common squamous type of NSCLC. Between 85 percent and 90 percent of all lung cancers are NSCLC, and more than two-thirds of those are the non-squamous type, according to the American Cancer Society.”

UPDATE 2-Bristol's Opdivo Proves Effective Against Second Type of Lung Cancer

“A large study of Bristol-Myers Squibb Co’s Opdivo treatment has been halted after proving the drug is effective against the most common form of lung cancer, the company said, positioning the medicine for far wider use than its already approved lung cancer and melanoma indications.

“The U.S. drugmaker on Friday said the study, called Checkmate-057, was stopped early after an independent data monitoring committee concluded that Opdivo provided a survival advantage over docetaxel, a standard chemotherapy, among patients with previously treated non-squamous non-small cell lung cancer (NSCLC).

“The so-called PD-1 inhibitor, which works by taking the brakes off the immune system, was approved by U.S. regulators last month to treat the less-common “squamous” form of NSCLC that had spread following treatment with chemotherapy.

“Opdivo is also approved for use against metastatic melanoma following treatment with Yervoy, another Bristol-Myers immuno-therapy.”

Biothera Immunotherapy Combination Results in Tumor Reduction During Maintenance Phase of Non-Small Cell Lung Cancer Study

“The combination of the investigational cancer immunotherapy Imprime PGG and the monoclonal antibody bevacizumab achieved additional meaningful reductions in tumor burden during the maintenance phase of Biothera’s recent phase 2 clinical trial in non-small cell lung cancer (NSCLC). The new data will be released today at the European Lung Cancer Conference.

“Biothera conducted a randomized Phase 2 clinical study in non-squamous NSCLC in which Imprime PGG was administered in combination with bevacizumab and platinum-based doublet chemotherapy. After four to six cycles of treatment, patients received maintenance therapy of bevacizumab with or without Imprime PGG. Further meaningful reductions in tumor burden (>10mm) were observed in 6 (20%) of patients in the Imprime PGG group, but not in the control group.

“ ‘Patients receiving the combination of Imprime PGG and bevacizumab experienced further reduction in their tumor burden than with bevacizumab therapy alone,’ said Ada Braun, M.D., Ph.D., Biothera Chief Medical Officer. ‘These results highlight the efficacy of Imprime PGG and show the potential for continued tumor regressions on chemotherapy-free maintenance therapy for some patients.’ ”

Necitumumab Offers No Benefit When Added to Chemotherapy in NSCLC Patients

“In the phase III INSPIRE trial reported in The Lancet Oncology, Paz-Ares et al found that the addition of the anti-EGFR IgG1 monoclonal antibody necitumumab to first-line pemetrexed (Alimta)-cisplatin did not improve overall survival in patients with previously untreated stage IV nonsquamous non–small cell lung cancer (NSCLC). Enrollment was stopped due to excess fatal and nonfatal thromboembolic events in the necitumumab group.

“In this open-label trial, 633 patients from 103 sites in 20 countries were randomly assigned between November 2009 and February 2011 to receive cisplatin at 75 mg/m² and pemetrexed at 500 mg/m² on day 1 of 3-week cycles for a maximum of six cycles with (n = 315) or without (n = 318) necitumumab at 800 mg on days 1 and 8 of each cycle. Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxicity. The primary endpoint was overall survival in the intention-to-treat population.

“Enrollment was stopped in February 2011 based on the observation of excess fatal and nonfatal thromboembolic events and overall number of deaths from all causes in the experimental group. Analysis indicated that most fatal thromboembolic events occurred within the first two cycles of therapy, with necitumumab thus being discontinued in patients who had not completed two cycles…

“The investigators concluded: ‘Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC. Unless future studies identify potentially useful predictive biomarkers, necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin.’ ”

OncoGenex and Sarah Cannon Announce Completion of Patient Enrollment in the Spruce™ Clinical Trial Evaluating Apatorsen in Combination with Carboplatin and Pemetrexed in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

“OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) and Sarah Cannon announced today that patient enrollment has been completed in the Spruce™ clinical trial, an investigator-sponsored, randomized, placebo-controlled Phase 2 trial evaluating apatorsen in combination with carboplatin and pemetrexed in patients with previously untreated, advanced, non-squamous, non-small cell lung cancer (NSCLC). Spruce is sponsored and led by Sarah Cannon Research Institute (SCRI), the research arm of Sarah Cannon, Hospital Corporation of America’s (HCA) global cancer enterprise, and is being conducted at 16 sites across the United States.

“In the Spruce trial, approximately 155 patients were randomized to receive either apatorsen or placebo in combination with carboplatin and pemetrexed therapy. The primary objective of the trial is progression-free survival (PFS), with additional analyses to evaluate overall survival, tumor response rates, safety, tolerability and the effect of therapy on heat shock protein 27 (Hsp27) levels.

” ‘Despite advances in targeted therapies to treat lung cancer, the majority of patients lack specific biomarkers and chemotherapy remains a mainstay of treatment for these patients,’ stated David Spigel MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute and trial study chair. ‘The Spruce trial will enable us to better understand the role of apatorsen in treating NSCLC and its potential to delay or prevent treatment resistance and improve survival outcomes for these patients who urgently need more effective treatment options.’ “