1087P - Phase II study of niraparib in patients with advanced melanoma with homologous recombination pathway gene mutations

Background

There are a limited number of therapeutic options available for metastatic melanoma patients progressing on the checkpoint inhibitor(s) and BRAF-targeting drugs. Approximately 21-34% of metastatic melanomas harbor at least 1 molecular aberration in the HR pathway, considered pathogenic leading to HR deficiency. We conducted a phase II study of niraparib in this patient population to evaluate clinical activity.

Methods

In this single-arm, open-label trial, we assessed the overall response rate to niraparib in patients with HR-deficient, unresectable, metastatic melanoma. Eligibility required mutation in ARID1A/B, ARID2, ATM, ATR, ATRX, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCD2, MRN11A, RAD50, RAD51, RAD54B or PALB2 gene;, and progression after PD1-antibody or BRAF/MEK inhibitors if BRAF mutant. Niraparib was administered orally once daily at 300 mg or 200 mg, based on body weight and platelet count.

Results

Due to a slow accrual, the enrollment was discontinued after 14 patients were enrolled and treated. Nine patients were female, a median age was 71. Nine patients had ECOG performance status of 1. The subtypes of melanoma were desmoplastic (3), acral lentiginous (2), mucosal (4), uveal (4), unspecified (1). Stages of the disease were III (3 pts) and IV (11 pts). Among the 14 treated patients, 2 (14%) patients had a partial response, and 7 (50%) had a stable disease. The median PFS was 16 weeks (range, 0-96 weeks). Among 10 patients with non-uveal melanoma, 2 (20%) patients had a partial response with a time to progression of 24 weeks, each. Five (50%) patients had a stable disease lasting 16-98 weeks. None of 4 uveal melanoma patients had a response. There were no unexpected adverse events associated with niraparibe treatment. One responder with ARID1A mutation had detectable circulating tumor DNA at baseline, but it became undetectable during the treatment.

Conclusions

Despite the relatively small number of patients, niraparib showed potential benefits in metastatic melanoma with HR gene mutations, particularly in non-uveal melanoma. Further investigation of PARPi in combination with immunotherapy or other targeted therapy is warranted.

Clinical trial identification

NCT03925350.

Editorial acknowledgement

Legal entity responsible for the study

K. B. Kim.

Funding

GSK.

Disclosure

All authors have declared no conflicts of interest.