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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05415072




Registration number
NCT05415072
Ethics application status
Date submitted
8/06/2022
Date registered
10/06/2022

Titles & IDs
Public title
A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas
Scientific 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
Secondary ID [1] 0 0
2021-003380-95
Secondary ID [2] 0 0
CDYP688A12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Other cancer types
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DYP688

Experimental: Phase I: Dose Escalation - Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas

Experimental: Phase II: Tebe naive group - Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp

Experimental: Phase II: Tebe pre-treated - Patients with metastatic uveal melanoma that have been previously treated with tebentafusp

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


Treatment: Drugs: DYP688
Single agent DYP688
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I (Dose Escalation): Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Phase I (Dose Escalation): Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Timepoint [2] 0 0
9 months
Primary outcome [3] 0 0
Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations
Timepoint [3] 0 0
9 months
Primary outcome [4] 0 0
Phase II: Overall Response rate (ORR) per RECIST 1.1
Timepoint [4] 0 0
17 months
Secondary outcome [1] 0 0
Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC)
Timepoint [1] 0 0
26 months
Secondary outcome [2] 0 0
Phase I and Phase II: PK profile of DYP688 - Peak concentration (Cmax)
Timepoint [2] 0 0
26 months
Secondary outcome [3] 0 0
Phase I and Phase II: PK profile of DYP688 - Total body clearance (CL)
Timepoint [3] 0 0
26 months
Secondary outcome [4] 0 0
Phase I and Phase II: PK profile of DYP688 - Elimination half-life
Timepoint [4] 0 0
26 months
Secondary outcome [5] 0 0
Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies
Timepoint [5] 0 0
26 months
Secondary outcome [6] 0 0
Phase I (Dose Escalation): Best Overall Response (BOR) per RECIST v1.1
Timepoint [6] 0 0
9 months
Secondary outcome [7] 0 0
Phase I (Dose Escalation): Overall Response Rate (ORR) per RECIST v1.1
Timepoint [7] 0 0
17 months
Secondary outcome [8] 0 0
Phase II: Duration of response (DoR) per RECIST v1.1
Timepoint [8] 0 0
17 months
Secondary outcome [9] 0 0
Phase II: Progression free survival (PFS) per RECIST v1.1
Timepoint [9] 0 0
17 months
Secondary outcome [10] 0 0
Phase II: Disease Control Rate (DCR) per RECIST v1.1
Timepoint [10] 0 0
17 months
Secondary outcome [11] 0 0
Phase II: Overall Survival (OS)
Timepoint [11] 0 0
17 months
Secondary outcome [12] 0 0
Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Timepoint [12] 0 0
17 months
Secondary outcome [13] 0 0
Phase II: Frequency of dose interruptions, reductions, and discontinuations
Timepoint [13] 0 0
17 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2025
Actual
Sample size
Target
124
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
France
State/province [3] 0 0
Paris
Country [4] 0 0
Germany
State/province [4] 0 0
Essen
Country [5] 0 0
Germany
State/province [5] 0 0
Heidelberg
Country [6] 0 0
Netherlands
State/province [6] 0 0
Zuid Holland
Country [7] 0 0
Spain
State/province [7] 0 0
Madrid
Country [8] 0 0
Switzerland
State/province [8] 0 0
Zuerich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05415072