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

Prior treatment

• 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.

Other illness

• 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.
• 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.

• 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 (not applicable in countries where enrollment is restricted by the local health authority to patients ≥ 18 years of age). 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. If a biopsy is not medically feasible, exceptions may be considered after documented discussion with Novartis.
  • 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 all 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 all standard therapies or that has no satisfactory alternative therapies