Assessment of Safety and Efficacy of OPM-101 Combined With Anti-PD-1 in Patients With Advanced Melanoma Showing Resistance to Anti-PD-1

Plain-language summary

This is a phase 1b/2a study including a dose escalation part (Phase 1b) and an extension part (Phase 2a). Both parts will be open-label, multicenter study of OPM-101 combined with the anti-PD-1 pembrolizumab as per standard of care in patients with MM who have been receiving an anti-PD-1-based treatment and have shown resistance to it, as defined by the Society for Immunotherapy of Cancer (SITC) criteria (Kluger, 2020). The objective of the study is to assess whether the addition of OPM-101 will resensitisze the tumour to the anti-PD-1-based treatment. Potential patients will be screened for this study during the period between initial evidence of disease progression on anti-PD-1 treatment and the required radiographic confirmation of disease progression. The intent is to initiate treatment with OPM-101 once the suspicion of disease progression on anti-PD-1-based therapy is confirmed, and the patient has signed the study Information and Consent Form. No anti-PD-1-based treatment should be administered within 4 weeks prior to study treatment initiation. In the dose escalation part (Phase 1b) of the study, two different doses of OPM-101 will be evaluated (75 mg bid and 150 mg bid) in combination with pembrolizumab. Patients will receive the dose and regimen of pembrolizumab, as per the authorised product SmPC, in sequential cohorts using a 3 + 3 design, escalating if 0 of 3 (or 1 of 6) patients experience a dose-limiting toxicity (DLT) during the first 6 weeks of treatment and not escalating if 2 of 6 patients experience a DLT. The RP2D of OPM-101 for the second part of the study (Phase 2a) in combination with pembrolizumab will be based on the rate of DLTs, incidence and severity of Treatment-Related AEs (AEs) and SAEs, and frequency of dose holds, reductions and discontinuations. A Data and Safety Monitoring Board (DSMB) will assess the safety criteria and make recommendations about dose escalation/de-escalation during the Phase 1b part, and on the RP2D to be used for further patients in the Phase 2a. The selection of the dose level for the Phase 2a will be based on safety and on preliminary PK/PD or even trends of efficacy. The DSMB will also review periodically the data during the Phase 2a and make recommendations about the continuation of the study. The cohort expansion part (Phase 2a) of the study will be conducted once the Phase 1b is completed and a safe and tolerated dose (potentially 150 mg bid) has been determined. Patients will receive daily oral treatment with OPM-101, while taking pembrolizumab for at least 12 weeks, i.e., at the time of the radiographic assessment of the disease for the primary endpoint evaluation. Patients who show a treatment response with Disease Control (CR, PR or SD) at 12 weeks will continue treatment with \[OPM-101 + pembrolizumab\] up to 24 weeks, when the second radiographic disease assessment is performed.

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