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

July 27, 2026 updated by: Novartis Pharmaceuticals

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a First in Human (FIH), phase I/II, open label, multi-center study of DYP688 as a single agent. There will be two parts to this study: a phase I, dose escalation part followed by a phase II part. Dose escalation will be conducted in patients with MUM and other melanomas harboring GNAQ/11 mutations. Once the MTD and/or RD(s) is determined in the dose escalation part, the study may continue with a phase II part. The phase II part will be conducted in two groups of patients with MUM, a prior tebentafusp-treated group and a tebentafusp-naïve group. In addition to MUM, a third group of patients with non-uveal GNAQ/11 mutant melanomas may also be explored. This cohort may be opened based on emerging data from the dose escalation part of the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Novartis Investigative Site
  • France
      • Paris, France, 75231
        • Novartis Investigative Site
  • Germany
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
  • Netherlands
    • South Holland
      • Leiden, South Holland, Netherlands, 2333 ZA
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28050
        • Novartis Investigative Site
  • Switzerland
      • Zurich, Switzerland, 8091
        • Novartis Investigative Site
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloane Ketterin Cancer Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase I: Dose Escalation
Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas
Drug: DYP688
Single agent DYP688
Experimental: Phase II: Tebe naive group
Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp
Drug: DYP688
Single agent DYP688
Experimental: Phase II: Tebe pre-treated
Patients with metastatic uveal melanoma that have been previously treated with tebentafusp
Drug: DYP688
Single agent DYP688
Experimental: Phase II: Non-uveal melanoma
Optional Arm: To explore patients with non-uveal melanoma that harbor GNAQ or 11 mutations, based on emerging data from dose escalation
Drug: DYP688
Single agent DYP688

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase I (Dose Escalation): Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
Time Frame: 28 days
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)
Time Frame: 9 months
Assessment of safety of DYP688 as a single agent
9 months
Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations
Time Frame: 9 months
Assessment of tolerability of DYP688 as a single agent
9 months
Phase II: Overall Response rate (ORR) per RECIST 1.1
Time Frame: 17 months
ORR in Phase II will be evaluated by central review per RECIST 1.1.
17 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC)
Time Frame: 26 months
Pharmacokinetic (PK) parameters will be determined by non-compartmental methods using pharmacokinetic profile of DYP688.
26 months
Phase I and Phase II: PK profile of DYP688 - Peak concentration (Cmax)
Time Frame: 26 months
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of DYP688.
26 months
Phase I and Phase II: PK profile of DYP688 - Total body clearance (CL)
Time Frame: 26 months
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of DYP688.
26 months
Phase I and Phase II: PK profile of DYP688 - Elimination half-life
Time Frame: 26 months
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of DYP688.
26 months
Phase I (Dose Escalation): Best Overall Response (BOR) per RECIST v1.1
Time Frame: 9 months
Evaluation of preliminary anti-tumor activity of DYP688 as a single agent
9 months
Phase I (Dose Escalation): Overall Response Rate (ORR) per RECIST v1.1
Time Frame: 17 months
Evaluation of preliminary anti-tumor activity of DYP688 as a single agent
17 months
Phase II: Duration of response (DoR) per RECIST v1.1
Time Frame: 17 months
Evaluation of anti-tumor activity of DYP688 as a single agent
17 months
Phase II: Progression free survival (PFS) per RECIST v1.1
Time Frame: 17 months
Evaluation of anti-tumor activity of DYP688 as a single agent
17 months
Phase II: Disease Control Rate (DCR) per RECIST v1.1
Time Frame: 17 months
Evaluation of anti-tumor activity of DYP688 as a single agent
17 months
Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 17 months
Assessment of safety of DYP688 as a single agent
17 months
Phase II: Frequency of dose interruptions, reductions, and discontinuations
Time Frame: 17 months
Assessment of tolerability of DYP688 as a single agent
17 months
Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies
Time Frame: 26 months
Assess of immunogenicity (IG) of DYP688 as a single agent
26 months
Phase II: Overall Survival (OS)
Time Frame: 17 months
Evaluation of the effect of DYP688 as a single agent on overall survival
17 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 4, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CDYP688A12101
  • 2021-003380-95 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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