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

NCT05061134 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: D533AC000012024-512378-91-002021-001722-21
• Study Type: interventional
• Target: 194
• Locations: 11 countries
• Sites: 66

Brief 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.

Conditions

Melanoma

Keywords

Unresectable or Advanced Melanoma; Efficacy; Safety

Outcome Measures

Primary Outcomes (5)

• Main Study: Objective Response Rate (ORR)

  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.

  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)

• Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Center Tumor Region

  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.

  Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

• Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-area in the Invasive Margin Region

  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.

  Baseline, Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

• Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Center Tumor Region

  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.

  Baseline, On-treatment (Cycle 0 Day 7), and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

• Biopsy Study: Change From Baseline in CD8+ T-cells Tumour Infiltration-density in the Invasive Margin Region

  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.

  Baseline, and Off-treatment (Cycle 0 Day 15-28) (each cycle is 28 days)

Secondary Outcomes (13)

• Main Study and Biopsy Study: Duration of Response (DOR)

  Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

• Main Study and Biopsy Study: Time to Response

  Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

• Main Study and Biopsy Study: Percentage Change From Baseline in Tumour Size

  Main Study: at 16 weeks; Biopsy study: at 20 weeks

• Main Study and Biopsy Study: Progression Free Survival (PFS)

  Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

• Main Study and Biopsy Study: Overall Survival (OS)

  Cycle 1 Day 1 (each cycle is 28 days) until date of documented progression or data cut-off (2 years), whichever occurred first

Study Arms (4)

Main study: Ceralasertib + Durvalumab

EXPERIMENTAL

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; Biological: Durvalumab

Main study: Ceralasertib

EXPERIMENTAL

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

Biopsy Sub-study: Ceralasertib + Durvalumab

EXPERIMENTAL

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; Biological: Durvalumab

Biopsy study: Ceralasertib

EXPERIMENTAL

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

Interventions

Ceralasertib DRUG

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

Biopsy Sub-study: Ceralasertib + Durvalumab; Biopsy study: Ceralasertib; Main study: Ceralasertib; Main study: Ceralasertib + Durvalumab

Durvalumab BIOLOGICAL

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.

Biopsy Sub-study: Ceralasertib + Durvalumab; Main study: Ceralasertib + Durvalumab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (66)

Research Site

Los Angeles, California, 90024, United States

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Sacramento, California, 95816, United States

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San Francisco, California, 94143, United States

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Tampa, Florida, 33612, United States

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Lutherville-Timonium, Maryland, 21093, United States

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Nashville, Tennessee, 37232, United States

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Darlinghurst, 2010, Australia

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East Melbourne, 3002, Australia

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Herston, 4029, Australia

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Woolloongabba, 4102, Australia

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Belgium, 1200, Belgium

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Bruges, 8000, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Edmonton, Alberta, t6G1Z2, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Ste-Foy, Quebec, G1V 4G2, Canada

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Bobigny, 93009, France

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Boulogne-Billancourt, 92100, France

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Marseille, 13385, France

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Paris, 75010, France

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Pau, 64046, France

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Pierre-Bénite, 69310, France

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Poitiers, 86021, France

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Vandœuvre-lès-Nancy, 54511, France

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Villejuif, 94805, France

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Berlin, 10117, Germany

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Buxtehude, 21614, Germany

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Heidelberg, 69120, Germany

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Heilbronn, 74078, Germany

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Kiel, 24105, Germany

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Mainz, 55131, Germany

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München, 80337, Germany

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Regensburg, 93053, Germany

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Schwerin, 19049, Germany

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Tübingen, D-72076, Germany

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Candiolo, 10060, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Padua, 35128, Italy

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Perugia, 06156, Italy

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Roma, 00168, Italy

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Siena, 53100, Italy

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Brzozów, 36-200, Poland

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Gdansk, 80-214, Poland

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Krakow, 31-115, Poland

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Lodz, 93-513, Poland

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Poznan, 60-355, Poland

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Warsaw, 02-781, Poland

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Goyang, 410-769, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Barcelona, 08041, Spain

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Madrid, 28007, Spain

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Madrid, 28027, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Málaga, 29009, Spain

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Pamplona, 31008, Spain

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Pozuelo de Alarcón, 28223, Spain

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Cambridge, CB2 0QQ, United Kingdom

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Chelsea, SW3 6JJ, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Related Links

• D533AC00001\_CSP\_Redacted
• D533AC00001\_SAP\_Redacted
• D533AC00001\_CSR synopsis\_Redacted

MeSH Terms

Conditions

Melanoma

Interventions

ceralasertib; durvalumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: September 29, 2021
• Study Start: August 11, 2022
• Primary Completion: April 12, 2024
• Study Completion (Estimated): November 2, 2026
• Last Updated: July 31, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

AU (4); BE (4); FR (9); IT (7); CA (4); PL (6); US (6); ES (8); GB (4); KR (4); DE (10)