A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition

NCT05061134 · tracked via the Priya Life Science USA tracker

Sponsor

AstraZeneca

Phase

Phase 2

Started

2022-08-11

Last updated

2025-07-31

Condition(s) studied

Melanoma

Investigational drug(s) / intervention(s)

CeralasertibDurvalumab

Ceralasertib: Ceralasertib (240 mg) will be administered orally twice daily.

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.

Study summary

Main study: This is an open-label, phase 2 study that aims to evaluate the efficacy and safety/tolerability of ceralasertib, when administered as monotherapy and in combination with durvalumab in participants with unresectable or advanced melanoma and primary or secondary resistance to PD-(L)1 inhibition.

Eligibility

Sex

ALL

Min age

18 Years

Max age

130 Years

Healthy volunteers

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.

Primary outcome measure(s)

Main Study: Objective Response Rate (ORR) — Cycle 1 Day 1 (Each Cycle is 28 days) until objective disease progression or the last evaluable assessment in the absence of progression, or data cut-off (1 year 8 months)
ORR was defined as the proportion of participants who had a complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours \[RECIST\] 1.1) that is confirmed at least 4 weeks later. As per planned in protocol, this outcome measure was assessed only for main study.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region — Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline, on-treatment and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Invasive Margin Region — Baseline, Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region — Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline, on-treatment and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.
Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region — Baseline, and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)
Changes in CD8+ T-cell infiltration of tumours induced by ceralasertib monotherapy was assessed in baseline and off-treatment tumour biopsies As per planned in protocol, this outcome measure was assessed only for biopsy study.

Trial sites (66)

Facility	City	Region
Research Site	Los Angeles	California
Research Site	Sacramento	California
Research Site	San Francisco	California
Research Site	Tampa	Florida
Research Site	Lutherville-Timonium	Maryland
Research Site	Nashville	Tennessee
Research Site	Darlinghurst	Australia
Research Site	East Melbourne	Australia
Research Site	Herston	Australia
Research Site	Woolloongabba	Australia
Research Site	Belgium	Belgium
Research Site	Bruges	Belgium
Research Site	Ghent	Belgium
Research Site	Leuven	Belgium
Research Site	Edmonton	Alberta
Research Site	Toronto	Ontario
Research Site	Toronto	Ontario
Research Site	Ste-Foy	Quebec
Research Site	Bobigny	France
Research Site	Boulogne-Billancourt	France
Research Site	Marseille	France
Research Site	Paris	France
Research Site	Pau	France
Research Site	Pierre-Bénite	France
Research Site	Poitiers	France
Research Site	Vandœuvre-lès-Nancy	France
Research Site	Villejuif	France
Research Site	Berlin	Germany
Research Site	Buxtehude	Germany
Research Site	Heidelberg	Germany
Research Site	Heilbronn	Germany
Research Site	Kiel	Germany
Research Site	Mainz	Germany
Research Site	München	Germany
Research Site	Regensburg	Germany
Research Site	Schwerin	Germany
Research Site	Tübingen	Germany
Research Site	Candiolo	Italy
Research Site	Milan	Italy
Research Site	Naples	Italy

+ 26 more sites — see the full list on the official registry below.

On this site

📄 Imfinzi (durvalumab) drug profile →

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05061134 on ClinicalTrials.gov ↗ ← All trials in the USA