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.
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
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Single agent DYP688
Massachusetts General Hospital Hematology Oncology
Boston, Massachusetts, United States
Columbia University Medical Center- New York Presbyterian Onc Dept
New York, New York, United States
Memorial Sloane Kettering Cancer Center MSKCC
New York, New York, United States
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.
Time frame: 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
Time frame: 9 months
Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations
Assessment of tolerability of DYP688 as a single agent
Time frame: 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.
Time frame: 17 months
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.
Time frame: 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.
Time frame: 26 months
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Novartis Investigative Site
Westmead, New South Wales, Australia
Novartis Investigative Site
Melbourne, Victoria, Australia
Novartis Investigative Site
Paris, France
Novartis Investigative Site
Essen, Germany
Novartis Investigative Site
Heidelberg, Germany
Novartis Investigative Site
Leiden, South Holland, Netherlands
Novartis Investigative Site
Madrid, Spain
...and 1 more locations
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.
Time frame: 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.
Time frame: 26 months
Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies
Assess of immunogenicity (IG) of DYP688 as a single agent
Time frame: 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
Time frame: 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
Time frame: 17 months
Phase II: Duration of response (DoR) per RECIST v1.1
Evaluation of anti-tumor activity of DYP688 as a single agent
Time frame: 17 months
Phase II: Progression free survival (PFS) per RECIST v1.1
Evaluation of anti-tumor activity of DYP688 as a single agent
Time frame: 17 months
Phase II: Disease Control Rate (DCR) per RECIST v1.1
Evaluation of anti-tumor activity of DYP688 as a single agent
Time frame: 17 months
Phase II: Overall Survival (OS)
Evaluation of the effect of DYP688 as a single agent on overall survival
Time frame: 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
Time frame: 17 months
Phase II: Frequency of dose interruptions, reductions, and discontinuations
Assessment of tolerability of DYP688 as a single agent
Time frame: 17 months