1130P - Phase II trial on nivolumab plus radiotherapy in patients with metastatic mucosal melanoma: PORTER-M3 trial

Background

The response rate for nivolumab alone in mucosal melanoma is limited to about 20%. Combined radiotherapy has been reported to increase the effectiveness of immune checkpoint inhibitors. The objective of this phase II trial was to evaluate the efficacy and safety of nivolumab in combination with radiotherapy for metastatic mucosal melanoma.

Methods

Eligibility criteria were as follows: histological diagnosis of metastatic mucosal melanoma; age ≧ 20 years; ECOG performance status 0 or 1; and with measurable lesions. Patients received nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks with concurrent radiotherapy to measurable lesions for a total dose of 25 Gy/5 fractions/week. The primary endpoint was the response rate (RR) according to Response Evaluation Criteria in Solid Tumors version 1.1. The study was considered to have met its primary endpoint if 6 or more of the 16 patients had a response (RR, 37.5%≦). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and toxicity.

Results

Eighteen patients were enrolled between July 2018 and March 2022. Two patients were excluded from the efficacy analysis because they were not assessed for efficacy. The RR was 43.8%. Two patients achieved a complete response, 5 did partial response, and 4 did stable disease as their best response. The median PFS was 4.9 months (95% confidence interval, 2.2 to 15.1). The median OS was 20.1 months (95% CI, 7.5 to 31.5). Treatment-related adverse events of grades 3 or 4 occurred in 35.2% (6/17) of the patients. Radiation-related adverse events were grade 3 radiation dermatitis in one patient and grade 3 radiation pneumonitis in one patient.

Conclusions

Concurrent immune-radiotherapy consisting of nivolumab and radiotherapy showed promising efficacy with a manageable safety profile for patients with metastatic mucosal melanoma, and warrants further evaluation in large studies.

Clinical trial identification

UMIN000030533; jRCT1051200028, March 1, 2018.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Nomura: Financial Interests, Personal, Advisory Board: Ono pharmaceutical co. ltd; Financial Interests, Personal, Invited Speaker: Ono pharmaceutical co. ltd, MSD, Bristol Myers Squibb. S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, Ltd, Taiho Pharmaceutical Co, Ltd, Bristol Myers Squibb, MSD Japan, Eisai Co, Ltd, Nippon Kayaku Co,Ltd, Asahi Kasei Pharma Co; Financial Interests, Institutional, Funding: Kyo Diagnostics Co, Ltd. M. Muto: Financial Interests, Personal, Invited Speaker: Chugai, MSD, Ono pharma, Meiji Seika Pharma, Novartis, Taiho; Non-Financial Interests, Advisory Role: KBBM, PRiME-R. All other authors have declared no conflicts of interest.