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

NCT07040436 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: OPM101-P2-01
• Study Type: interventional
• Target: 41
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Advanced Melanoma

Keywords

OPM-101; Melanoma; resistance; Anti-PD1; RIPK2; advanced; immuno-oncology; anti-PD1 refractory; pembrolizumab

Outcome Measures

Primary Outcomes (2)

• Determination of the recommended dose

  In the phase 1b: the recommended dose for phase 2a will be based on the independent assessement of safety of OPM-101 by the DSMB

  6 weeks

• Determination of the Disease Control Rate (DCR)

  In phase 2a, Disease Control Rate defined as CR, PR or SD as per RECIST v.1.1 criteria

  12 weeks

Secondary Outcomes (5)

• Determination of the Disease Control Rate

  12 weeks

• Determination of the Disease Control Rate

  24 weeks

• Determination of the objective response rate (ORR)

  Week 12 and Week 24

• Determination of the frequency of dose reduction, and discontinuations

  24 weeks

• Safety assessments

  24 weeks

Other Outcomes (7)

• Biomarker: Cytokine evaluation

  24 weeks

• Biomarker: Chemokine evaluation

  24 weeks

• Pharmacokinetics parameters (Cmax)

  Day 1

Study Arms (1)

OPM-101 (in combination with pembrolizumab)

EXPERIMENTAL

OPM-101 will be administered as hard gelatin capsules twice a day for 24 weeks. In the Phase 1b, 2 doses of OPM-101 will be considered: 75 mg bid and 150 mg bid. At the end of this Phase 1b, a recommended dose for Phase 2a will be determined. During the Phase 2a, the recommended dose of OPM-101 will be administered bid over 24 weeks. OPM-101 will be administered in combination with authorized regimen of Pembrolizumab.

Drug: OPM-101

Interventions

OPM-101 DRUG

OPM-101 will be administered in combination with an authorized regimen of Pembrolizumab. Pembrolizumab will be administered by IV infusion either at a dose of 200 mg every 3 weeks or at a dose of 400 mg every 6 weeks, as per Principal Investigator's decision.

OPM-101 (in combination with pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent provided prior to any study-related procedure.
• Histologically confirmed, unresectable or metastatic stage III or IV melanoma.
• At least one measurable lesion per RECIST v.1.1 criteria.
• Patients with a documented and confirmed Progressive Disease with an anti-PD-1-based treatment given alone or in combination (except combination with an anti-LAG-3 drug). Progressive disease will be determined by the PI based on the SITC v3.0 guidelines.
• Patients with no anti-PD-1-based treatment administration within 4 weeks (or 6 weeks for a treatment with pembrolizumab administered with a 400 mg q6w scheme) prior to study treatment initiation.
• Patients accepting to undergo a fresh biopsy at baseline and after 12 weeks of treatment (for Phase 1b only).
• In case a fresh baseline biopsy collection would represent a medical risk for the patient, an archival biopsy could be used, after discussion with the Medical Monitor and the Principal Investigator (PI)
• If archival sample is unavailable, and the patient cannot provide a fresh tumour biopsy at baseline due to medical risk or inaccessibility, the patient may still be enrolled if agreed upon between the Investigator and the Sponsor.
• Male or female patients ≥18 years.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1.
• Estimated life expectancy ≥3 months.
• Adequate hematologic parameters and organ function defined by:
• white blood cell count ≥3,000/µL
• absolute neutrophil count ≥1,500/µL without support of filgrastim
• platelet count ≥75,000/µL

You may not qualify if:

• Diagnosis of primary uveal and/or ocular melanoma, as well as mucosal melanoma
• Active leptomeningeal disease or uncontrolled brain metastasis. Patients with equivocal findings or with confirmed brain metastases are eligible for enrolment provided they are asymptomatic without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s).
• Patients who have received any line of therapy with a BRAF inhibitor or MEK inhibitor in the advanced disease setting.
• Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
• weeks for any anti-PD-1-based therapy (except for previous treatments with pembrolizumab administered with a 400 mg q6w scheme for which the duration should be 6 weeks)
• weeks for radiation therapy
• weeks for limited field radiation for palliation
• weeks or 5 half-lives (whichever is longer) for continuous or intermittent small molecule therapeutics or any other investigational agent, receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device. The participation in the follow-up Phase (i.e., receiving no study treatment) of a prior study is allowed.
• weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C
• History of severe or life-threatening immune-related (IR) AEs during a previous treatment with anti-PD-1
• IR-myocarditis
• Grade ≥3, IR- interstitial lung disease IR-renal toxicity.
• Grade 4 for IR-maculopapular rash, IR-diarrhoea and enterocolitis, IR-rheumatological toxicity, IR-neuro(muscular) toxicity, IR-hepatotoxicity
• Unrecovered CTCAE at time of screening
• Any patient unrecovered to a CTCAE grade ≤2 for patients who has been pre-treated with anti-PD-1 monotherapy

Sponsors & Collaborators

• Oncodesign Precision Medicine: lead

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Bruno Robin, PharmD

CONTACT

+33 3 1045 1820; brobin@oncodesign.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label phase 1b/2a study

Study Record Dates

• First Submitted: June 13, 2025
• First Posted: June 27, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 27, 2025

Record last verified: 2025-06