A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition (MONETTE)
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| ClinicalTrials.gov Identifier: NCT05061134 |
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Recruitment Status :
Recruiting
First Posted : September 29, 2021
Last Update Posted : December 6, 2022
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Melanoma | Drug: Ceralasertib Biological: Durvalumab | Phase 2 |
Biopsy sub-study: This is an open-label, non-randomised, sub-study planned in participants suitable for 3 mandatory biopsies. Serial tumour biopsies are mandated in participants recruited into the sub-study and will be taken at baseline during the screening period, during treatment with ceralasertib monotherapy and during the off-treatment period of ceralasertib monotherapy.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 195 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | August 11, 2022 |
| Estimated Primary Completion Date : | March 29, 2024 |
| Estimated Study Completion Date : | March 29, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
MedlinePlus related topics:
Melanoma
Drug Information available for:
Durvalumab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Ceralasertib
Ceralasertib (240 mg) will be administered orally twice daily. Biological: 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. |
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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.
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Drug: Ceralasertib
Ceralasertib (240 mg) will be administered orally twice daily. |
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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.
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Drug: Ceralasertib
Ceralasertib (240 mg) will be administered orally twice daily. Biological: 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. |
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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.
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Drug: Ceralasertib
Ceralasertib (240 mg) will be administered orally twice daily. |
Primary Outcome Measures :
- Main study: Objective response rate (ORR) [ Time Frame: 8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years) ]
ORR is the proportion of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
1 cycle length is 28 days.
- Biopsy sub-study: CD8+ T-cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies [ Time Frame: Screening, on-treatment and off-treatment during Cycle 1 ]
Changes in CD8+ T cell infiltration of tumours induced by ceralasertib monotherapy will be evaluated.
1 cycle length is 28 days.
Secondary Outcome Measures :
- Main study and Biopsy sub-study: Duration of Response (DoR) [ Time Frame: Main study: 8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years); Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years) ]
DoR will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause.
1 cycle length is 28 days.
- Main study and Biopsy sub-study: Time to objective response (TTR) [ Time Frame: Main study: 8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years); Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years) ]
Time to response is defined as the time from randomisation (or date of first dose of study treatment, for the biopsy sub-study) until the date of first documented objective response, which is subsequently confirmed per RECIST 1.1 as assessed by BICR.
1 cycle length is 28 days.
- Main study and Biopsy sub-study: Percentage change in target lesion tumour size [ Time Frame: Main study: 16 weeks; Biopsy study: 20 weeks ]
Percentage change from baseline in tumor lesions tumour size, where tumor size is the sum of the longest diameters of the target lesions.
1 cycle length is 28 days.
- Biopsy sub-study: ORR [ Time Frame: Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years) ]
ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by BICR per RECIST 1.1.
1 cycle length is 28 days.
- Main study and Biopsy sub-study: Progression free survival (PFS) [ Time Frame: From screening until objective disease progression or death (approx. up to 1 year) ]PFS is defined as time from randomisation (or date of first dose for the biopsy sub-study) until progression per RECIST 1.1 as assessed by BICR or death due to any cause.
- Main study and Biopsy sub-study: Overall survival (OS) [ Time Frame: From screening until death (approx. up to 2 years) ]OS is defined as time from randomisation (or date of first dose for the biopsy sub-study) until the date of death due to any cause
- Biopsy sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50 [ Time Frame: Biopsy study: Screening, on-treatment and off-treatment during Cycle 1 ]
Tumour tissue samples for the analysis of tumoural biomarkers that change following treatment with ceralasertib will collected.
1 cycle length is 28 days.
- Main study and Biopsy sub-study: Number of adverse events and serious adverse events [ Time Frame: From screening until treatment discontinuation plus 90 day safety follow up (approx. up to 1 year) ]Adverse events will recorded to evalute the safety and tolerability of the study drugs.
- Main study: Concentration of ceralasertib in plasma [ Time Frame: Cycle 1, 2, 3 Day 7 (each cycle is 28 days) ]To assess the Pharmakokinetic (plasma peak and trough concentrations) of ceralasertib alone and when in combination with durvalumab.
- Biopsy sub-study: Assessment of proliferation of carcinoma in Ki67 marker (Marker Of Proliferation Ki-67) or CD8+ T cells immune cells [ Time Frame: From baseline, on-treatment and off-treatment until 24 months after the last patient (approx 2 years) ]To assess changes in the proliferation of carcinoma and/or immune cells within tumours induced by ceralasertib monotherapy.
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| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05061134
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 76 study locations
Sponsors and Collaborators
AstraZeneca
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT05061134 |
| Other Study ID Numbers: |
D533AC00001 2021-001722-21 ( EudraCT Number ) |
| First Posted: | September 29, 2021 Key Record Dates |
| Last Update Posted: | December 6, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by AstraZeneca:
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Unresectable or Advanced Melanoma Efficacy Safety |
Additional relevant MeSH terms:
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Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Nerve Tissue Nevi and Melanomas Durvalumab Antineoplastic Agents, Immunological Antineoplastic Agents |