Save

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

PHASE1PHASE2RECRUITING

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.

Simpliy with AI

Study details:

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.

Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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.

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.

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-07-04

Primary completion: 2025-09-30

Study completion finish: 2025-09-30

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05415072

Intervention or treatment

DRUG: DYP688

Conditions

• Metastatic Uveal Melanoma

Image related to Metastatic Uveal Melanoma

Condition: Metastatic Uveal Melanoma
DRUG: DYP688
Melbourne, Victoria, Australia
Sponsor: Novartis Pharmaceuticals

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Novartis Investigative Site

Research sites nearby

Select from list below to view details:

Novartis Investigative Site
Melbourne, Victoria, Australia

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?

Participant Group/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

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC)	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)	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)	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	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of DYP688.	26 months
Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies	Assess of immunogenicity (IG) of DYP688 as a single agent	26 months
Phase I (Dose Escalation): Best Overall Response (BOR) per RECIST v1.1	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	Evaluation of preliminary anti-tumor activity of DYP688 as a single agent	17 months
Phase II: Duration of response (DoR) per RECIST v1.1	Evaluation of anti-tumor activity of DYP688 as a single agent	17 months
Phase II: Progression free survival (PFS) per RECIST v1.1	Evaluation of anti-tumor activity of DYP688 as a single agent	17 months
Phase II: Disease Control Rate (DCR) per RECIST v1.1	Evaluation of anti-tumor activity of DYP688 as a single agent	17 months
Phase II: Overall Survival (OS)	Evaluation of the effect of DYP688 as a single agent on overall survival	17 months
Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	Assessment of safety of DYP688 as a single agent	17 months
Phase II: Frequency of dose interruptions, reductions, and discontinuations	Assessment of tolerability of DYP688 as a single agent	17 months

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

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