Merkel Cell Carcinoma is an aggressive cutaneous malignancy associated with Merkel cell polyomavirus or UV exposure. In recent years, anti-PD1/PDL1 therapy has dramatically improved the treatment landscape, but outcome remains poor among patients who progress on this therapy.
In this multicenter phase 2 randomized study, patients with unresectable, recurrent or metastatic Merkel cell carcinoma patients received NIVO 240mg IV q2 wks plus IPI 1mg/kg IV q6 wks (Arm A) or NIVO 240mg IV q2 wks plus IPI 1mg/kg IV q6 wks plus stereotactic body radiation therapy (SBRT) to 24Gy in 3 fractions at week 2 (Arm B). Patients were required to have at least two measurable sites of disease to ensure that at least one non-irradiated site could be followed for treatment response. Both arms were experimental and randomized in a 1:1 ratio based on a Bayesian pick-the-winner design with each arm using a Simon’s Mini-Max two-stage design. Patients were stratified by prior treatment with immune checkpoint inhibitor (ICI). The primary endpoint was objective response rate (ORR). Tumor status was assessed every 12 weeks and evaluated by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).
50 patients (24 ICI-naïve, 26 with prior ICI) received ≥1 dose of NIVO plus IPI and 24 received SBRT (median follow-up 14.6 months). ORR in ICI-naïve patients was 100% [95%CI, 82%-100%], 41% with complete response. ORR in prior ICI patients was 31% [95%CI, 15%-52%], 15% with complete response. No significant differences in ORR were observed between Arms A and B (72% vs. 52%, p=0.26). Median duration of response was not reached [95%CI, 33.9 months-NE] in the ICI-naïve cohort and was 10.8 months [95% CI, 4.9 months-NE] in the prior ICI cohort. Treatment was well tolerated with a toxicity profile similar to that previously observed.
In this study, first-line therapy with NIVO plus IPI in patients with advanced MCC demonstrated an exceptionally high ORR of 100%, with durable responses and a manageable safety profile. NIVO plus IPI also exhibited clinical activity in patients who progressed on prior anti-PD1/PDL1 monotherapy. Addition of SBRT did not alter the efficacy of NIVO plus IPI in this study.
Clinical trial identification
Legal entity responsible for the study
H. Lee. Moffitt Cancer Center.
Bristol Myers Squibb.
S. Kim: Other, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca. E. Wuthrick: Other, Institutional, Advisory Role: Viewray, Varian, AlphaTau, Castle Biosciences, Teiko. J. Caudell: Other, Institutional, Funding: Varian, Galera. A. Tarhini: Financial Interests, Personal, Advisory Board: Bristol Myers Squib, Genentech/Roche, Easai, Instil Bio, Clinigen, Regeneron, Sanofi-Genzyme, Novartis, Partner Therapeutics, BioNTech, Merck; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squib; Financial Interests, Institutional, Invited Speaker: Genentech-Roche, Nektar, Checkmate, InflaRx; Financial Interests, Institutional, Research Grant: Regeneron, Sanofi-Genzyme, Clinigen, Acrotech, Pfizer, OncoSec. J. Markowitz: Other, Institutional, Funding: Merck, Microba, Jackson Laboratory, Morphogenesis. V. Sondak: Other, Institutional, Advisory Board: Bristol-Myers-Squibb, Eisai, Iovance, Merck, Novartis, Regeneron, Statking; Other, Institutional, Funding: Neogene, Turnstone. N.I. Khushalani: Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb, Regeneron Pharmaceuticals, Merck, Iovance Biotherapeutics, Genzyme, Nektar, Castle Biosciences, Instil Bio, Novartis; Financial Interests, Personal, Other, Data Safety Monitoring Committee: Incyte, Astra-Zeneca; Financial Interests, Personal, Stocks/Shares: Amarin, Asensus Surgical, Bellicum; Financial Interests, Institutional, Invited Speaker: Bristol Myers-Squibb, Merck, Novartis, GlaxoSmithKline, HUYA, Regeneron, Celgene, Replimmune; Financial Interests, Personal, Invited Speaker: Bristol Myers-Squibb, Regeneron, Nektar; Financial Interests, Invited Speaker: Replimmune; Non-Financial Interests, Principal Investigator, Global clinical trial: Huya. A. Brohl: Other, Institutional, Advisory Board: Deciphera, Bayer. All other authors have declared no conflicts of interest.