Overview

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.