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

NCT05415072 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CDYP688A121012021-003380-95
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 11

Brief 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.

Conditions

Metastatic Uveal Melanoma

Keywords

Phase I/II; DYP688; melanoma; GNAQ/11 mutations; cancer; malignant melanoma; eye cancer; ocular melanoma; uveal melanoma; cutaneous melanoma; mucosal melanoma; neoplasms, eye

Outcome Measures

Primary Outcomes (4)

• Phase I (Dose Escalation): Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.

  A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle of treatment with DYP688. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

• Phase I (Dose Escalation): Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

  Assessment of safety of DYP688 as a single agent

  9 months

• Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations

  Assessment of tolerability of DYP688 as a single agent

  9 months

• Phase II: Overall Response rate (ORR) per RECIST 1.1

  ORR in Phase II will be evaluated by central review per RECIST 1.1.

  17 months

Secondary Outcomes (13)

• Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC)

  26 months

• Phase I and Phase II: PK profile of DYP688 - Peak concentration (Cmax)

  26 months

• Phase I and Phase II: PK profile of DYP688 - Total body clearance (CL)

  26 months

• Phase I and Phase II: PK profile of DYP688 - Elimination half-life

  26 months

• Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies

  26 months

Study Arms (4)

Phase I: Dose Escalation

EXPERIMENTAL

Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas

Drug: DYP688

Phase II: Tebe naive group

EXPERIMENTAL

Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp

Drug: DYP688

Phase II: Tebe pre-treated

EXPERIMENTAL

Patients with metastatic uveal melanoma that have been previously treated with tebentafusp

Drug: DYP688

Phase II: Non-uveal melanoma

EXPERIMENTAL

Optional Arm: To explore patients with non-uveal melanoma that harbor GNAQ or 11 mutations, based on emerging data from dose escalation

Drug: DYP688

Interventions

DYP688 DRUG

Single agent DYP688

Phase I: Dose Escalation; Phase II: Non-uveal melanoma; Phase II: Tebe naive group; Phase II: Tebe pre-treated

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• weeks for fluoropyrimidine therapy
• weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.
• 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.
• weeks for cytotoxic agents with major delayed toxicities, such as nitrosoureas and mitomycin C.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Massachusetts General Hospital Hematology Oncology

Boston, Massachusetts, 02114, United States

Location

Columbia University Medical Center- New York Presbyterian Onc Dept

New York, New York, 10032, United States

Location

Memorial Sloane Kettering Cancer Center MSKCC

New York, New York, 10065, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Leiden, South Holland, 2333, Netherlands

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma; Neoplasms; Eye Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 10, 2022
• Study Start: July 4, 2022
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 20, 2025

Record last verified: 2025-07

Locations

DE (2); NL (1); CH (1); FR (1); ES (1); AU (2); US (3)