Much-anticipated trial results were presented on the third day of the annual meeting of the American Society of Clinical Oncology, held in Chicago. These included phase 3 results from the CheckMate 067 trial and a phase 2 study with elotuzumab.
Checkmate 67 Results Push Nivolumab Closer to First-Line in Melanoma
The much-anticipated results from phase 3 of the CheckMate 067 trial were presented during the Plenary Session on the third day of the annual meeting of the American Society of Clinical Oncology, being held at the McCormick Convention Center, Chicago, May 29-June 2, 2015. A late-breaking abstract “Efficacy and safety results from a phase III trial of nivolumab alone or combined with ipilimumab versus ipilimumab alone in treatment-naive patients with advanced melanoma,” was presented by Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center.
Checkmate 67 is a randomized, double-blind study, designed to evaluate the efficacy of nivolumab as first-line therapy in advanced melanoma, alone or in combination with ipilimumab.
The trial methods were as follows: 945 treatment-naïve patients, a majority of whom were male, were randomized to receive either nivolumab alone, ipilimumab alone, or nivolumab and ipilimumab, until progression or unacceptable toxicity. Patients were stratified by PD-L1 status, BRAF mutation status, and disease stage. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR) and safety. During the Plenary session, Dr Wolchok reported PFS and ORR data; patients are being followed to estimate OS.
At a minimum follow-up of 9 months, Dr Wolchok said that patients treated with the combination of nivolumab and ipilimumab as well as those treated with nivolumab alone, had significantly improved PFS and ORR, compared with patients treated with ipilimumab alone.
Median PFS (months)
CR rate (%)
Further, a higher number of patients treated with the combination had a partial response, compared with nivolumab or ipilimumab alone. While progressive disease was highest with ipilimumab and lowest with the combination, duration of response had not been reached because the follow-up period was not long enough.
When the response rate was analyzed in relation to high PD-L1 expression, Dr Wolchok said that the combination treatment resulted in a higher response rate (72.1%) compared to nivolumab alone (57.5%). Similar trends were observed with low PD-L1 expressing tumors.
Safety profile of the combination, he said, was consistent with earlier results, and the combination did show higher incidence of adverse events. There were no new safety signals or drug-related deaths observed with the combination, while the monotherapies had 1 death each. “The current evidence suggests that the combination presents a means to improve outcomes versus using nivolumab alone, especially in patients with low (<5%) PD-L1 expression,” Dr Wolchok concluded.
Elotozumab Presents Promise in Multiple Myeloma
A poster presented on the second day of the annual meeting of the American Society of Clinical Oncology, Chicago, May 29-June 2, 2015, evaluated the advantage of incorporating the monoclonal antibody, elotuzumab, in a treatment regimen of bortezomib/dexamethasone, in relapsed/refractory multiple myeloma (RRMM) patients. These results were from a phase 2 open-label study, from 83 centers across the United States and Europe, including 152 patients.
Interaction of elotuzumab with the signaling lymphocytic activation molecule F7, results in myeloma cell death, with minimal effects on normal tissue. Previous studies from a preclinical myeloma model found enhanced activity of elotuzumab when combined with bortezomib, as well as good phase 1 results. This study investigated the efficacy and safety of elotuzumab ± bortezomib/dexamethasone in RRMM patients.
The primary endpoint of the study was to compare PFS between the treatment arms in the intent-to-treat population, and the secondary objective was to estimate differences in response rates between the arms. The researchers also intended to explore safety, time to response, duration of response, and OS.
Patients with RRMM who had progressed on at least 1-3 prior therapies, and who met Eastern Cooperative Oncology Group status ≤ 2 were eligible for participation.
The authors showed that the study met its primary endpoint of PFS: median PFS was 9.7 months in the elotozumab/bortezomib/dexamethasone—treated group versus 6.9 months when elotuzumab was left out. ORR was 65% when elotuzumab was included in the treatment, versus 63% when it was not. The 1-year OS rate was 85% versus 74%, with and without elotuzumab, respectively.
At the time of analysis, 40 patients had died due to disease progression, of which 17 were on the elotuzumab/bortezomib/dexamethasone arm. The authors did not see any differences in adverse events between the 2 trial arms.
Based on this analysis, the authors concluded that the study met the primary endpoint. Elotuzumab significantly improved PFS when combined with bortezomib/dexamethasone, and elotuzumab—treated patients had a 28% reduction in their risk of disease progression. The authors think the available OS data is encouraging as well. Long-term outcomes studies are ongoing.
Jakubowiak AJ, Offidani M, Pegourie B, et al. A randomized phase II study of bortezomib (Btz)/dexamethasone (dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). 2015. J Clin Oncol. 33(suppl): abstract 8573.