A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas

• Status: Not yet recruiting
• Trial end date: 2025-11-04
• Target enrollment: 0
• Participant gender: All

Summary

This is a FIH, phase I/II, open label, multi-center study of DYP688 as a single agent. The purpose of this study is to characterize the safety, tolerability, and anti-tumor activity of DYP688 as a single agent in patients with metastatic uveal melanoma (MUM) and other melanomas harboring GNAQ/11 mutations.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

Inclusion Criteria:

• Patients in the dose escalation part must be ≥ 18 years of age at the time of informed consent (ICF) signature. In the phase II part, patients ≥ 12 years of age at the time of informed consent may be eligible for enrollment. Patients must have a minimum weight of 40 kg.

• ECOG performance status ≤ 1 for patients ≥ 18 years of age; Karnofsky performance status ≥ 70 for patients ≥ 16 and < 18 years of age; Lansky performance status ≥ 70 for patients ≥ 12 and < 16 years of age

• Patients must be suitable and willing to undergo study required biopsies according to the treating institution's own guidelines and requirements.

For all patients in Dose Escalation

• MUM: uveal melanoma with histologically or cytologically confirmed metastatic disease. Patient must be either treatment naive or have received any number of prior lines and progressed on most recent therapy

• Non-MUM: advanced cutaneous or mucosal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies and has evidence of GNAQ/11 mutation based on local data

For patients in Phase II

• Tebentafusp naïve group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies

• Tebentafusp pre-treated group: Diagnosis of uveal melanoma with histologically or cytologically confirmed metastatic disease. Patients must be previously treated with tebentafusp and have progressed

• Non-MUM: patients with diagnosis of cutaneous or mucosal melanomas harboring GNAQ/11 mutations based on local data, with histologically or cytologically confirmed metastatic disease that has progressed following standard therapies or that has no satisfactory alternative therapies

Exclusion Criteria:

• Malignant disease, other than that being treated in this study.

• Active brain metastases, i.e. symptomatic brain metastases or known leptomeningeal disease.

• Evidence of active bleeding or bleeding diathesis or significant coagulopathy (including familial) or a medical condition requiring long term systemic anticoagulation that would interfere with biopsies.

• History of anaphylactic or other severe hypersensitivity / infusion reactions to ADCs or monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.

• Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:

• 2 weeks for fluoropyrimidine therapy

• 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.

• 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.

• 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C.

• 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.

• Clinically significant and / or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade ≥ 2) or clinically significant arrhythmia despite medical treatment.

Other protocol-defined inclusion/exclusion criteria may apply.