A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas
Metastatic Uveal Melanoma
About this trial
This is an interventional treatment trial for Metastatic Uveal Melanoma focused on measuring Phase I/II, DYP688, melanoma, GNAQ/11 mutations, cancer, malignant melanoma, eye cancer, ocular melanoma, uveal melanoma, cutaneous melanoma, mucosal melanoma, neoplasms, eye
Eligibility 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.
Sites / Locations
- Massachusetts General Hospital Hematology OncologyRecruiting
- Columbia University Medical Center- New York Presbyterian Onc DeptRecruiting
- Memorial Sloane Kettering Cancer Center MSKCCRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Phase I: Dose Escalation
Phase II: Tebe naive group
Phase II: Tebe pre-treated
Phase II: Non-uveal melanoma
Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas
Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp
Patients with metastatic uveal melanoma that have been previously treated with tebentafusp
Optional Arm: To explore patients with non-uveal melanoma that harbor GNAQ or 11 mutations, based on emerging data from dose escalation