A Study of Ceralasertib Monotherapy and Ceralasertib plus Durvalumab in Patients with Melanoma and Resistance to PD-(L)1 Inhibition - MONETTE

Study identifier:D533AC00001

ClinicalTrials.gov identifier:NCT05061134

EudraCT identifier:2021-001722-21

CTIS identifier:N/A

Recruitment Complete

Official Title

A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib plus Durvalumab in Patients with Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition

Medical condition

Melanoma

Phase

Phase 2

Healthy volunteers

Study drug

Ceralasertib

Sex

All

Actual Enrollment

194

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 11 Aug 2022

Estimated Primary Completion Date: 12 Apr 2024

Estimated Study Completion Date: 12 Apr 2024

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Participants must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype
- Availability of an archival tumour sample and a fresh tumour biopsy taken at screening
- Patient must have received at least 1 prior immunotherapy (anti-PD-(L)1 ± anti-CTLA-4 [Cytotoxic T-lymphocyte-associated protein 4]) for a minimum of 6 weeks and no more than 2 prior regimens in the metastatic setting. Patients must have confirmed progression during treatment with a PD-(L)1 inhibitor +/- a CTLA-4 inhibitor.
- The interval between the last dose of anti-PD-(L)1, BRAF/MEK (B-Rapidly Accelerated Fibrosarcoma gene/mitogen-activated protein kinase gene) inhibitor and the first dose of the study regimen must be a minimum of 14 days
- Measurable disease by RECIST 1.1.
- Patients must have a life expectancy ≥3 months from proposed first dose date.
- Biopsy Sub-study: Consent to the provision of 3 mandatory tumour biopsies.

Exclusion Criteria

- Patients must not have experienced a toxicity that led to permanent discontinuation of prior checkpoint inhibitors (CPI) treatment.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 3 years before the first dose of study treatment
- Uveal melanoma
- Must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy
- History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead.
- History of organ transplant that requires use of immunosuppressive medications
- Inadequate bone marrow and impaired hepatic or renal function
- Known active infection requiring systemic therapy, active hepatitis infection, positive hepatitis C virus antibody, hepatitis B virus (HBV) surface antigen or HBV core antibody (anti-HBc), at screening
- Patients with confirmed COVID-19 infection by polymearse chain reaction test who have not made a full recovery.

No locations available

Arms	Assigned Interventions
Experimental: Main study: Ceralasertib + Durvalumab Participants will receive ceralasertib on Days 1 to 7 plus durvalumab Day 8, once in 28 days (Q28D), until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.	Drug: Ceralasertib Ceralasertib (240 mg) will be administered orally twice daily. Biological/Vaccine: Durvalumab Durvalumab (1500 mg) will be administered intravenously once every 28 days for participants who weight above > 30 kgs. For participants who weigh below ≤ 30 kgs, weight-based dosing equivalent to 20 mg/kg of durvalumab will be administered.
Experimental: Main study: Ceralasertib Participants will receive ceralasertib on Days 1 to 7, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.	Drug: Ceralasertib Ceralasertib (240 mg) will be administered orally twice daily.
Experimental: Biopsy Sub-study: Ceralasertib + Durvalumab From Cycle 1, participants will receive combination of ceralasertib twice daily (BD) Days 1 to 7 plus durvalumab Day 8, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or a study treatment discontinuation criterion is met.	Drug: Ceralasertib Ceralasertib (240 mg) will be administered orally twice daily. Biological/Vaccine: Durvalumab Durvalumab (1500 mg) will be administered intravenously once every 28 days for participants who weight above > 30 kgs. For participants who weigh below ≤ 30 kgs, weight-based dosing equivalent to 20 mg/kg of durvalumab will be administered.
Experimental: Biopsy study: Ceralasertib During Cycle 0, participants will receive ceralasertib on Days 1 to 7, followed by an off-treatment period between Days 8 to 28.	Drug: Ceralasertib Ceralasertib (240 mg) will be administered orally twice daily.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]