Study of DYP688 in participants with metastatic uveal melanoma (MUM) or other GNAQ/11 mutant melanomas

Australia, France, Germany, Netherlands, Spain, Switzerland, United States (ICTRP)

ID di studio ICTRP
NCT05415072 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A Phase I/II, multi-center, open label study of DYP688 in patients with metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas (BASEC)

Titolo accademico
A Phase I/II, Multi-center, Open Label Study of DYP688 in Patients With Metastatic Uveal Melanoma (MUM) and Other GNAQ/11 Mutant Melanomas (ICTRP)

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

Malattie studiate
Metastatic Uveal Melanoma (ICTRP)

Intervento studiato
Drug: DYP688 (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Gender: All
Maximum age: N/A
Minimum age: 18 Years
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 na?ve 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. (ICTRP)

non disponibile

Endpoint primari e secondari
Phase I (Dose Escalation): Incidence and severity of dose limiting toxicities (DLTs) during the first 28 days of treatment.;Phase I (Dose Escalation): Incidence and severity of adverse events (AEs) and serious adverse events (SAEs);Phase I (Dose Escalation): Frequency of dose interruptions, reductions, and discontinuations;Phase II: Overall Response rate (ORR) per RECIST 1.1 (ICTRP)

Phase I and Phase II: PK profile of DYP688 - Area under the concentration-time curve (AUC);Phase I and Phase II: PK profile of DYP688 - Peak concentration (Cmax);Phase I and Phase II: PK profile of DYP688 - Total body clearance (CL);Phase I and Phase II: PK profile of DYP688 - Elimination half-life;Phase I and Phase II: Prevalence and incidence of anti-DYP688 antibodies;Phase I (Dose Escalation): Best Overall Response (BOR) per RECIST v1.1;Phase I (Dose Escalation): Overall Response Rate (ORR) per RECIST v1.1;Phase II: Duration of response (DoR) per RECIST v1.1;Phase II: Progression free survival (PFS) per RECIST v1.1;Phase II: Disease Control Rate (DCR) per RECIST v1.1;Phase II: Overall Survival (OS);Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs);Phase II: Frequency of dose interruptions, reductions, and discontinuations (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Novartis Pharmaceuticals, novartis.email@novartis.com, 1-888-669-6682 (ICTRP)

ID secondari
2021-003380-95, CDYP688A12101 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT05415072 (ICTRP)