Testing DYP688 for metastatic uveal melanoma and other GNAQ/11 mutant melanomas

A Phase I/II, Multi-center, Open Label Study of DYP688 in Patients With Metastatic Uveal Melanoma (MUM) and Other GNAQ/11 Mutant Melanomas

This study is testing a new drug called DYP688 to see if it can help people with advanced uveal melanoma and other types of melanoma that have specific gene mutations.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 124 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Novartis (industry)
• Drugs / interventions: chemotherapy, radiation
• Locations: 11 sites (Boston, Massachusetts and 10 other locations)
• Trial ID: NCT05415072 on ClinicalTrials.gov

What this trial studies

This is a Phase I/II, open-label, multi-center study evaluating the safety, tolerability, and anti-tumor activity of DYP688 in patients with metastatic uveal melanoma and other melanomas with GNAQ/11 mutations. The study consists of a dose escalation phase to determine the maximum tolerated dose, followed by a phase II part that includes groups of patients who have previously been treated with tebentafusp and those who have not. Additionally, a cohort of patients with non-uveal GNAQ/11 mutant melanomas may be included based on findings from the dose escalation phase.

Who should consider this trial

Good fit: Ideal candidates include patients aged 12 years and older with metastatic uveal melanoma or other GNAQ/11 mutant melanomas who meet specific health criteria.

Not a fit: Patients without GNAQ/11 mutations or those with other types of melanoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with metastatic uveal melanoma and GNAQ/11 mutant melanomas.

How similar studies have performed: Other studies targeting GNAQ/11 mutations have shown promise, but this specific approach with DYP688 is novel.

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 (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

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.

Where this trial is running

Boston, Massachusetts and 10 other locations

• Massachusetts General Hospital Hematology Oncology — Boston, Massachusetts, United States (RECRUITING)
• Columbia University Medical Center- New York Presbyterian Onc Dept — New York, New York, United States (RECRUITING)
• Memorial Sloane Kettering Cancer Center MSKCC — New York, New York, United States (RECRUITING)
• Novartis Investigative Site — Westmead, New South Wales, Australia (RECRUITING)
• Novartis Investigative Site — Melbourne, Victoria, Australia (RECRUITING)
• Novartis Investigative Site — Paris, France (RECRUITING)
• Novartis Investigative Site — Essen, Germany (RECRUITING)
• Novartis Investigative Site — Heidelberg, Germany (RECRUITING)
• Novartis Investigative Site — Leiden, Zuid Holland, Netherlands (RECRUITING)
• Novartis Investigative Site — Madrid, Spain (RECRUITING)
• Novartis Investigative Site — Zuerich, Switzerland (RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Metastatic Uveal Melanoma, Phase I/II, DYP688, melanoma, GNAQ/11 mutations, cancer, malignant melanoma, eye cancer