Patients with advanced non-small cell lung cancer (NSCLC) who have never received chemotherapy, may benefit from combination of the immunotherapy agents Opdivo (nivolumab) and Yervoy (ipilimumab), according to updated data from the CheckMate -012 Phase 1b trial.
The data were presented orally at the International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer (WCLC), held Dec. 4-7, in Vienna, Austria.
The multi-arm Phase 1 CheckMate -012 trial was designed to assess the safety and tolerability of Opdivo alone, or in combination with several other cancer therapies, including tyrosine kinase inhibitors, anti-angiogenic drugs, chemotherapy agents or the immunotherapy agent Yervoy, in chemotherapy-naive advanced NSCLC patients.
Participants included in the Opdivo-plus-Yervoy group were included in four dose cohorts receiving different doses and schedules of therapies. The study’s primary endpoint was safety and tolerability, and secondary endpoints included overall response rate and 24-week progression-free survival. Exploratory endpoints included overall survival and efficacy by expression of the PD-L1 protein.
Data presented in June at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting revealed a manageable safety profile and an overall response rate in the Opdivo-plus-Yervoy cohorts that ranged from 13% to 39%. Median duration of response not reached at the time of data cut-off. Importantly, patients responded to therapy regardless of PD-L1 expression, even though those who expressed high levels of this protein showed more benefit.
Now, Bristol-Myers Squibb has provided updated results on this study, revealing data from a pooled analysis of the Opdivo-plus-Yervoy combination cohorts. The new findings show that, after 16 months of follow-up, patients with PD-L1 expression of 1% or more have a median progression-free survival of 12.7 months, and this was not reached for patients with PD-L1 expression of 50% percent or higher.
Importantly, the one-year overall survival rate for patients with 50% or more PD-L1 expression was 100%, and 87% in the 1% or greater PD-L1 expression group. In addition, objective response rate was 43% in all treated patients, which was nearly double those observed in Opdivo monotherapy (23%). Six patients achieved complete responses, three of which had PD-L1 expression lower than 1%.
“With longer follow-up in the CheckMate -012 trial, we observe that the Opdivo and Yervoy combination resulted in encouraging progression-free survival,” Scott N. Gettinger, MD, associate professor of medicine, Yale Cancer Center, said in a press release. “We are also excited to see the consistent near doubling of response rates with the combination relative to Opdivo alone in both PD-L1 expressors and non-expressors, and the previously reported response rates of over 50% and 90%, respectively, among patients with at least 1% and 50% tumor PD-L1 expression. We look forward to further evaluating Opdivo plus Yervoy in the first line treatment setting for advanced lung cancer,” he said.
“The updated results from CheckMate -012 continue to be promising, and we look forward to advancing the Opdivo-and-Yervoy combination in the ongoing CheckMate -227 Phase 3 trial for first-line advanced lung cancer, with the hope of confirming these findings,” added Nick Botwood, MD, development lead, Lung (Division), Bristol-Myers Squibb.