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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT05415072

Studienbeginn:
Juli 2022

Letztes Update:
29.04.2024

Wirkstoff:
DYP688

Indikation (Clinical Trials):
Melanoma, Uveal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 11)

Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Columbia University Medical Center- New York Presbyterian Onc Dept
10032 New York
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Caitlin Rogers
Phone: 212-885-0878
E-Mail: cr3311@cumc.columbia.edu» Ansprechpartner anzeigen
Novartis Investigative Site
2145 Westmead
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
2300 RC Leiden
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
8091 Zuerich
SwitzerlandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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:

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

Studien-Arme

  • 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

Geprüfte Regime

  • DYP688:
    Single agent DYP688

Quelle: ClinicalTrials.gov


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