Several New Drugs Approved in Top Oncology News
Top recent news in cancer drug development.
Top recent news in cancer drug development.
Nivolumab Approved for mRCC
The FDA approved nivolumab as a treatment for patients with metastatic renal cell carcinoma following prior anti-angiogenic therapy, based on an extension in overall survival in the CheckMate-025 trial. The approval for nivolumab follows a breakthrough therapy designation and was granted nearly 4 months ahead of schedule.
In the pivotal data, nivolumab reduced the risk of death by 27% versus everolimus, representing a 5.4-month improvement in median OS. Grade 3/4 adverse events were also lower with the PD-1 inhibitor compared with everolimus. The median OS was 25.0 months with nivolumab versus 19.6 months with everolimus (HR, 0.73; P = .002).
The OS benefit was observed across patient subgroups and PD-L1 did not appear to impact outcomes. Median PFS was 4.6 and 4.4 months in the nivolumab and everolimus arms, respectively (HR, 0.88; P = .11). In an ad hoc sensitivity analysis of patients who had not progressed at 6 months, the median PFS was 15.6 months with nivolumab versus 11.7 months with everolimus (HR, 0.64).
This analysis was meant to take pseudoprogression into consideration. The ORR with nivolumab was 21.5% compared with 3.9% for those receiving everolimus.
The duration of response in the nivolumab arm was 23.0 months compared with 13.7 months with everolimus, according to the FDA.
FDA Approves Ixazomib for Myeloma
Acting almost 4 months ahead of schedule, the FDA approved the oral proteasome inhibitor ixazomib in combination with lenalidomide and dexamethasone as a treatment for patients with multiple myeloma who have received at least one prior therapy. The approval was based on data from the 722-patient phase III TOURMALINE-MM1 trial, which showed a median progression-free survival of 20.6 months with ixazomib plus lenalidomide and dexamethasone compared with 14.7 months with lenalidomide and dexamethasone alone (HR, 0.74; P = .012).
For those with high-risk cytogenetics, the benefit with ixazomib was more pronounced, with a 46% improvement in PFS (HR, 0.54). The objective response rate with ixazomib was 78.3% compared with 71.5% for lenalidomide and dexamethasone alone (odds ratio [OR], 1.44; P = .035). The complete response rate with ixazomib was 11.7% versus 6.6% with the doublet (OR, 1.87; P = .019).
The rate of very good partial response or better was 48.1% versus 39.0%, with and without ixazomib, respectively (OR, 1.45; P = .014). Interestingly, serious AEs occurred in 40% of patients treated with ixazomib compared with 44% without the proteasome inhibitor. Additionally data from this study will be presented at the ASH Annual Meeting.
Dabrafenib and Trametinib Granted Full Approval for BRAF+ Melanoma
The FDA granted a full approval to the combination of dabrafenib and trametinib for patients with unresectable or metastatic BRAF-mutated melanoma, based on an extension in overall survival from two phase III studies. The FDA initially granted an accelerated approval to the combination for patients with BRAF-mutant melanoma in January 2014, based on objective response rates.
The FDA based its decision on earlier analyses from the COMBI-d and v trials. In the COMBI-v analysis, the median OS had not yet been reached in the combination arm. For single-agent vemurafenib, the median OS was 17.2 months. Median progression-free survival with the combination was 11.4 versus 7.3 months with vemurafenib alone (HR, 0.56; P <.001).
In the earlier COMBI-d analysis, the median OS with dabrafenib plus trametinib was 25.1 versus 18.7 months with dabrafenib alone (HR, 0.71; P = .01). The median PFS was 9.3 months with the combination versus 8.8 months with dabrafenib alone (HR, 0.75; P = .035). Across both studies, the combination was found to induce fewer adverse events compared with either agent alone.
FDA Advisory Panel Votes Against MCNA for Bladder Cancer
An FDA panel voted 18 to 6 against approval of the immunotherapy MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin therapy. The panel, which included members of the FDA’s ODAC and CTGTAC committees, considered a biologics license application for MCNA that is primarily based on findings from the open-label phase III trial EN3348-301 (Study 301), which failed to meet its primary endpoint.
With its vote, the panel concluded that the risks of MCNA outweigh the potential benefit. In Study 301, 25% of patients treated with MCNA remained disease-free at 1-year, and at 2-years, the disease-free survival rate was 19%. However, the primary endpoint of the study was a 1-year DFS rate of ≥40%.
Additionally, the FDA, using a responder landmark analysis, calculated a 1-year DFS of 20.9%, also lower than the primary endpoint. A final decision from the FDA on MCNA is scheduled by February 27, 2016.
Avelumab Granted Breakthrough Status for Merkel Cell Carcinoma
The FDA has granted a breakthrough therapy designation to avelumab as a potential treatment for patients with metastatic Merkel cell carcinoma following progression on at least one prior chemotherapy regimen, according to a statement from the companies codeveloping the PD-L1 inhibitor, Merck KGaA and Pfizer.
Avelumab (formally MSB0010718C) is a fully human IgG1 antibody being co-developed across a variety of settings. In addition to inhibiting PD-L1, avelumab is also thought to elicit a response from the innate immune system to induce antibody-dependent cell-mediated cytotoxicity. The new designation for avelumab was based on preliminary findings from the phase II JAVELIN Merkel 200 study.
Although data from this study has not yet been released, findings from this trial have also led to fast track and orphan drug designations from the FDA for avelumab. Findings from the phase II study are being prepared for presentation at an upcoming conference in 2016.
Rindopepimut OS Advantage Extended in Longer Analysis
Treatment with the immunotherapy rindopepimut plus bevacizumab resulted in a 47% reduction in the risk of death compared with bevacizumab and a control for patients with relapsed glioblastoma multiforme, according to an updated analysis of the phase II ReACT trial presented at the 2015 Society for Neuro-Oncology Annual Meeting. In the updated findings for overall survival, 25% of patients treated with rindopepimut remained alive at 2-years compared with none in the control arm.
The median OS with rindopepimut was 11.3 versus 9.3 months in the control arm (HR, 0.53; P = .0137). The 6-month PFS rate with rindopepimut was 28% versus 16% with the control (one sided P = .1163), which met the primary endpoint for the study. The boundary for one side significant was 0.2.
By expert review, the ORR with rindopepimut was 30% compared with 18% in the control arm. According to investigator assessment, ORR was 23% and 9%, for rindopepimut and the control, respectively. In the rindopepimut arm at 2 months, 50% of patients were able to stop taking corticosteroids versus 26% in the control arm. By ≥6 months, 33% of patients had reduced or stopped steroid use versus none with the control.
Vemurafenib/Cobimetinib OS Data Presented at SMR
Treatment with the combination of vemurafenib and cobimetinib improved overall survival by 4.9 months compared with vemurafenib alone for patients with BRAF mutation-positive advanced melanoma, according to findings from the phase III coBRIM study presented at the 2015 Society for Melanoma Research Congress. In the updated findings, the median OS was 22.3 months with the combination compared with 17.4 months with vemurafenib alone, representing a 30% reduction in the risk of death (HR, 0.70; P = .005).
The 1- and 2-year OS rates with the combination were 74.5% and 48.3%, respectively. On November 10, 2015, the FDA approved the combination of vemurafenib and cobimetinib as a treatment for patients with BRAF-positive metastatic or unresectable melanoma, based on an extension in progression-free survival in the phase III coBRIM study. An approval decision from the European Commission is anticipated before the end of 2015.
The final OS data from the coBRIM study are being submitted to both regulatory agencies for potential label updates for the combination.
Nivolumab OS Benefit Maintained With Longer Follow-Up
Long-term data continue to show sustained improvements in overall survival with nivolumab alone or in combination with ipilimumab as a frontline treatment for patients with advanced melanoma, according to two presentations at the 2015 Society for Melanoma Research Congress. In the phase III CheckMate-066 trial, the 2-year OS rate with frontline nivolumab was 57.7% compared with 26.7% for dacarbazine.
Additionally, in a phase Ib study, the combination of nivolumab and ipilimumab showed an OS rate of 68% at a median follow-up of 32.7 months. The FDA is currently reviewing an application for nivolumab as frontline therapy for patients with advanced melanoma, based on the CheckMate-066 trial. The agency is scheduled to make a decision regarding the application by November 27, 2015. After a minimum follow-up of 15.1 months, median OS was not yet reached for patients receiving nivolumab compared with 11.2 months in the dacarbazine arm (HR, 0.43; P <.001).
The 1-year OS rates were 70.7% and 46.3%, for nivolumab and dacarbazine, respectively. Additionally, following progression in the dacarbazine arm, 13% of patients (n = 27) went on to receive nivolumab. In the smaller phase Ib study, labeled Study 004, the 18-month OS rate was 68%. The ORR was 44%, with complete responses in 17% of patients. The median duration of response was 13.7 months.