5715 - A Phase 2, Randomized Study of Nivolumab (NIVO) and Ipilimumab (IPI) versus NIVO, IPI and Stereotactic Body Radiation Therapy (SBRT) for Metastatic Merkel Cell Carcinoma (MCC, NCT03071406) – a preliminary report.

Background

MCC is an aggressive cutaneous malignancy. Though checkpoint inhibitor therapy has dramatically improved the treatment landscape, outcome remains poor for those that are refractory to anti-PD1/PDL1 therapy. Combination checkpoint inhibition and the use of radiation therapy have been proposed as potentially synergistic interventions to improve immunotherapy (IT) response rates (RR).

Methods

In this multi-institutional trial, we enrolled patients (pts) with metastatic or recurrent MCC, ECOG PS 0-1, with at least 2 distinct metastatic lesions. Prior chemotherapy or immunotherapy was permitted. Primary endpoint was objective RR. In a randomized design of 2 experimental arms, pts received NIVO 240mg IV q2 wks plus IPI 1mg/kg IV q6 wks (arm A), or the same combination plus SBRT to 24Gy in 3 fractions between cycles 1 and 2 (arm B). Each arm uses a Simon Mini-Max two-stage design for futility, with total accrual of 50 assuming full accrual.

Results

To date, 16 pts have been enrolled, including 4 treatment-naïve and 12 PD1/PDL1-refractory pts. 11 pts were male and 5 pts female. Median age at enrollment was 75.5. On Arm A, the RR was 80% (1 CR, 3 PR) in 4/5 evaluable pts. On Arm B, the RR was 17% (1 PR) among 6 evaluable pts. 4 pts are pending initial staging and 1 pt expired prior to first evaluation. Collectively, 2/8 (25%) PD1/PDL1refractory pts and 3/3 (100%) IT-naïve pts have achieved CR/PR. 7 pts experienced > G2 immune toxicity (1 G3 myocarditis, 1 G3 colitis, 1 G2 arthritis, 1 G2 cough, 3 G2 dermatitis, 1 G2 neurotoxicity, 1 G2 blurred vision, 1 G2 abdominal pain, 2 G2 hypothyroidism, 1 G2 renal insufficiency). 1 pt was taken off the trial due to toxicity.

Conclusions

NIVO + IPI is safe and demonstrates promising initial efficacy in advanced MCC in both PD1/PDL1-naïve and refractory cases. SBRT can be safely added to this and its contribution to efficacy is being explored pending futility analysis. Arm A of the trial has already met efficacy criteria to proceed to full accrual.

Clinical trial identification

NCT03071406.

Editorial acknowledgement

Legal entity responsible for the study

H. Lee. Moffitt Cancer Center & Research Institute.

Funding

Bristol-Myers Squibb.

Disclosure

S. Kim: Research grant / Funding (institution), IIT funded through BMS rare malignancy program: BMS. N.I. Khushalani: Advisory / Consultancy: BMS. L. Harrison: Research grant / Funding (self): Viewray. All other authors have declared no conflicts of interest.