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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05415072
Recruitment Status : Recruiting
First Posted : June 10, 2022
Last Update Posted : March 22, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Uveal Melanoma Drug: DYP688 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Multi-center, Open Label Study of DYP688 in Patients With Metastatic Uveal Melanoma (MUM) and Other GNAQ/11 Mutant Melanomas
Actual Study Start Date : July 4, 2022
Estimated Primary Completion Date : March 12, 2026
Estimated Study Completion Date : March 13, 2026

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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

  3. Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations [ Time Frame: 9 months ]
    Assessment of tolerability of DYP688 as a single agent

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Phase II: Overall Survival (OS) [ Time Frame: 17 months ]
    Evaluation of the effect of DYP688 as a single agent on overall survival

  12. 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

  13. Phase II: Frequency of dose interruptions, reductions, and discontinuations [ Time Frame: 17 months ]
    Assessment of tolerability of DYP688 as a single agent


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05415072


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
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United States, Massachusetts
Massachusetts General Hospital Hematology Oncology Recruiting
Boston, Massachusetts, United States, 02114
Contact: Brielle Salvo    617-643-3614    bsalvo@mgh.harvard.edu   
Principal Investigator: Ryan Sullivan         
United States, New York
Columbia University Medical Center- New York Presbyterian Onc Dept Recruiting
New York, New York, United States, 10032
Contact: Samantha Petruzzelli    212-304-5579    sp4099@cumc.columbia.edu   
Principal Investigator: Shaheer Khan         
Memorial Sloane Kettering Cancer Center MSKCC Recruiting
New York, New York, United States, 10065
Contact: Alexander Shoushtari       shoushta@mskcc.org   
Principal Investigator: Alexander Shoushtari         
Australia, New South Wales
Novartis Investigative Site Recruiting
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
France
Novartis Investigative Site Recruiting
Paris, France, 75231
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Netherlands
Novartis Investigative Site Recruiting
Leiden, Netherlands, 2300 RC
Spain
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Switzerland
Novartis Investigative Site Recruiting
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05415072    
Other Study ID Numbers: CDYP688A12101
2021-003380-95 ( EudraCT Number )
First Posted: June 10, 2022    Key Record Dates
Last Update Posted: March 22, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Phase I/II
DYP688
melanoma
GNAQ/11 mutations
cancer
malignant melanoma
 eye cancer
ocular melanoma
uveal melanoma
cutaneous melanoma
mucosal melanoma
neoplasms, eye
Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
 Neoplasms, Nerve Tissue
Nevi and Melanomas
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Uveal Diseases