SITC 2016: Phase I/II Data Combining Urelumab With Nivolumab Suggest Increased Antitumor Effect in Patients With Melanoma
Safety and efficacy data from a phase I/II study of urelumab in combination with nivolumab (Opdivo) in patients with hematologic and solid tumors, including biomarker analyses by level of programmed death ligand 1 (PD-L1) expression, was recently presented at the Society for Immunotherapy of Cancer (SITC) 31st Annual Meeting in National Harbor, Maryland (poster number 239).
Urelumab is a fully human monoclonal IgG4k antibody agonist of CD137, a tumor necrosis factor family receptor expressed primarily on activated T cells and activated natural killer (NK) cells.
About the Study
The phase I/II study of urelumab administered in combination with nivolumab evaluated which doses are safe and tolerable. Efficacy was evaluated in advanced/metastatic melanoma (n = 46), diffuse large B-cell lymphoma (DLBCL, n = 19), non–small cell lung cancer (NSCLC) patients who had progressed on a PD-1/PD-L1 therapy (n = 14), NSCLC patients who had not previously received a PD-1/PD-L1 therapy (n = 20), squamous cell carcinoma of the head and neck (n = 22), and other tumors (n = 3). The objective response rate for these cohorts was 50%, 0%, 0%, 5%, 5%, and 0%, respectively, and the disease control rate was 70%, 21%, 21%, 35%, 23%, and 33%, respectively.
After an initial phase where patients received urelumab 3 mg IV every 4 weeks plus nivolumab 3 mg/kg IV every 2 weeks, patients were treated with urelumab 8 mg IV every 4 weeks plus nivolumab 3 mg/kg IV every 2 weeks. Cohort expansion, during which patients with specific tumor types received urelumab 8 mg IV every 4 weeks plus nivolumab 240 mg IV every 2 weeks, was initiated after completion of the required safety monitoring period.
The primary endpoint of the study is safety, as measured by the rate of adverse events and serious adverse events. All subjects who received at least one (full or partial) dose of urelumab or nivolumab were evaluated for safety during treatment and for up to 100 days follow-up (n = 138). Secondary outcome measures include best overall response, objective response rate, duration of response, and progression-free survival rate.
Findings
The combination of urelumab and nivolumab showed encouraging efficacy among 46 evaluable melanoma patients with an objective response rate of 50% (23/46 with 18 confirmed and 5 unconfirmed). Objective response rate was a secondary endpoint as measured by Response Evaluation Criteria in Solid Tumors (RECIST). Similar response was seen in both PD-L1 positive and PD-L1 negative melanoma patients, with objective response rate of 50% (10/20) and 47% (8/17) in those with ≥ 1% and < 1% PD-L1 expression, respectively.
Among the other cohorts (n = 78), one patient with NSCLC and one patient with squamous cell carcinoma of the head and neck had an objective response. In the full patient population (n = 138), no significant added toxicity was observed with urelumab in combination with nivolumab over nivolumab monotherapy.
The overall rate of treatment-related adverse events was 63% (n=87), with the most common being fatigue (31%), ALT increased (11%), anemia (10%), and AST increased (9%). No additional signals were seen with the combination therapy compared to nivolumab monotherapy. The rate of Grade 3–4 treatment-related adverse events was 17% (n=23). The rate of discontinuations due to treatment-related adverse events was 6% (n=8).
“These results suggest that urelumab in combination with nivolumab may offer an antitumor benefit in patients with melanoma, in both PD-L1 expressors and nonexpressors,” said Erminia Massarelli, MD, PhD, MS, Associate Clinical Professor at the City of Hope Comprehensive Cancer Center. “While there have been major advances in melanoma treatment over the past 5 years, some patients continue to need additional options to treat the disease, which is one of deadliest forms of cancer.”
This study is sponsored and run by Bristol Myers Squibb Company.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
