Interim results of nivolumab + rucaparib in SCLC

Interim results of a phase 2 study suggest that patients with extensive-stage small-cell lung cancer (SCLC) and platinum sensitivity may be good candidates for maintenance treatment with immune checkpoint inhibitors (ICI) and poly adenosine diphosphate-ribose polymerase inhibitors (PARPi), in this particular study, nivolumab and rucaparib [1].

Preclinical studies have demonstrated that PARPi possesses cytotoxic activity as a single-agent and in combination with ICI in SCLC; however, this combination has not been tried to date as first-line therapy for SCLC. Investigators hypothesised that adding a PARPi to ICI therapy could enhance the efficacy of the ICI. To this end, a phase 2 trial (NCT03958045) evaluated the response and survival rates associated with the administration of nivolumab and rucaparib to patients with extensive-stage SCLC.

The trial recruited patients (n=20) with stage 4 extensive-stage SCLC who had achieved either a partial response or complete response following treatment with platinum-based chemotherapy. Participants were excluded if they had undergone prior ICI therapy.  The starting dose of oral rucaparib was 600 mg twice daily; nivolumab was administered as an intravenous infusion once every 4 weeks at a fixed dose of 480 mg. The primary endpoint was progression-free survival (PFS) after response to initial platinum-based therapy.

Dr Aman Chauhan (University of Kentucky, KY, USA) presented interim data from the trial. All enrolled patients had achieved a partial response in accordance with Response Evaluation Criteria in Solid Tumours (RESIST) v1.1. The median PFS from initiation of maintenance therapy was 2.67 months; the median PFS from time of diagnosis on frontline therapy, which included treatment with chemotherapy followed by maintenance rucaparib and nivolumab, was 7.27 months. Dr Chauhan emphasised that 25% of patients remained on maintenance therapy.

No deaths occurred during the study. One patient withdrew from the trial due to grade 4 hepatotoxicity.

Dr Chauhan concluded that the combination of ICI and PARPi therapy seems to be well tolerated at the time of this interim analysis. Investigators are currently evaluating immune predictors of a durable response. Trial completion is anticipated in December 2021.

1. Chauhan A. A phase 2 study of frontline rucaparib + nivolumab in platinum sensitive ES SCLC: Interim analysis. OA 07.03, WCLC 2021, 8–14 September.

 

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Posted on 21 September, 202125 March, 2024