DURVALUMAB for Unresectable melanoma | Advanced melanoma

Inclusion criteria

• {"criterion_text":"-Patient must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype"}
• {"criterion_text":"-Biopsy Sub-Study: Lesions used for biopsy may have received prior radiation therapy only if there is documented evidence of progression in the lesion after radiation treatment"}
• {"criterion_text":"-Availability of an archival tumour sample and a fresh tumour biopsy taken at screening."}
• {"criterion_text":"-Patient must have received at least 1 prior immunotherapy (anti-PD- (L)1 ± anti-CTLA-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."}
• {"criterion_text":"-No intervening treatment eg, investigational therapy is permitted between the anti-PD-(L)1 therapy and study treatment"}
• {"criterion_text":"-BRAF V600E or V600K mutation status must be known at screening"}
• {"criterion_text":"-Measurable disease by RECIST 1.1."}
• {"criterion_text":"-Biopsy Sub-Study: Consent to the provision of 3 mandatory tumour biopsies."}
• {"criterion_text":"-Biopsy Sub-Study: Have at least 1 tumour lesion medically accessible for 3 biopsies at baseline, on ceralasertib treatment and off ceralasertib treatment. Accessible lesions are defined as tumour lesions which are amenable to biopsy, unless clinically contraindicated or the patient has withdrawn consent. It is preferable that the same lesion is used for each biopsy, but if this is not possible, a patient may enrol if they have more than 1 lesion that is suitable for biopsy from the same tissue type eg, 3 cutaneous lesions"}
• {"criterion_text":"-Biopsy Sub-Study: Lesions used for biopsy should be different from those used as RECIST lesions, unless there are no other lesions suitable for biopsy"}

Exclusion criteria

• {"criterion_text":"-Patients must not have experienced a toxicity that led to permanent discontinuation of prior CPI treatment."}
• {"criterion_text":"-Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment"}
• {"criterion_text":"-Uveal melanoma"}
• {"criterion_text":"-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."}
• {"criterion_text":"-Active or prior documented autoimmune or inflammatory disorders (including, but not limited to inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, irritable bowel disease, Wegner syndrome, Hashimoto syndrome, hyperthyroidism, Sjogren's syndrome, glomerulonephritis, multiple sclerosis, vasculitis, rheumatoid arthritis, idiopathic pulmonary fibrosis, pneumonitis, organising pneumonia, hepatitis, sarcoidosis, active tuberculosis) within the past 3 years"}
• {"criterion_text":"-Inadequate bone marrow and impaired hepatic or renal function."}
• {"criterion_text":"-Biopsy Sub-Study: Patients must comply with the exclusion criteria described for the main study"}
• {"criterion_text":"-Biopsy Sub-Study: Patients with evidence of bleeding disease deemed unsafe for serial biopsies"}

Primary endpoints

• {"endpoint_text":"-The primary measure is the estimate of ORR for each experimental treatment arm, and a secondary measure of interest is the odds ratio of the ORR comparing the 2 treatment arms.","definition_or_measurement_approach":"Assessment of objective response rate (ORR) in each experimental treatment arm (as stated: estimate of ORR for each arm)"}
• {"endpoint_text":"-Biopsy Sub-study: CD8+ T cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies.","definition_or_measurement_approach":"CD8+ T cell tumour infiltration assessed in tumour biopsies taken at baseline, on-treatment and off-treatment"}

Secondary endpoints

• {"endpoint_text":"-Median and landmark DoR estimates at 6, 9, 12, 15, and 18 months","definition_or_measurement_approach":"Duration of Response (DoR); median and landmark estimates at specified timepoints"}
• {"endpoint_text":"-Median TTR and proportion of patients with response at the first scheduled tumour assessment","definition_or_measurement_approach":"Time to objective response (TTR) median and proportion with response at first scheduled tumour assessment"}
• {"endpoint_text":"-Percentage change from baseline in TL tumour size at week 16 and best percentage change from baseline","definition_or_measurement_approach":"Change in target lesion tumour size (percent change) at week 16 and best percent change from baseline"}
• {"endpoint_text":"-Median and landmark PFS at 3, 6, 9, 12 months, and the hazard ratio comparing the 2 treatment arms","definition_or_measurement_approach":"Progression-free survival (PFS); median and landmark estimates and hazard ratio comparing treatment arms"}
• {"endpoint_text":"-Median and landmark OS at 6, 9, 12, and 18 months, and the hazard ratio comparing the 2 treatment arms","definition_or_measurement_approach":"Overall survival (OS); median and landmark estimates and hazard ratio comparing treatment arms"}
• {"endpoint_text":"-Concentration of ceralasertib in plasma (peak and trough concentrations, as data allow; sparse sampling)","definition_or_measurement_approach":"Plasma PK of ceralasertib: peak and trough concentrations (sparse sampling)"}
• {"endpoint_text":"-Biopsy Sub-study: As described for the main study, using the investigator assessment of tumour response per RECIST 1.1","definition_or_measurement_approach":"Tumour response assessed by investigator per RECIST 1.1 (for biopsy sub-study as for main study)"}
• {"endpoint_text":"-Biopsy Sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50","definition_or_measurement_approach":"Assessment of PD-L1 and pRAD50 expression in pre-treatment, on-treatment and off-treatment biopsies"}
• {"endpoint_text":"-Biopsy Sub-study: Proliferation (using Ki67+ marker) of carcinoma and/or immune cells (including CD8+ T cells) will be assessed in baseline, on-treatment and off-treatment tumour biopsies","definition_or_measurement_approach":"Assessment of proliferation (Ki67+) in carcinoma and/or immune cells in baseline, on-treatment and off-treatment tumour biopsies"}

Belgium

Latest Decision Or Authorization Date

08-08-2024

Number Of Sites

4

Number Of Participants

9

France

Latest Decision Or Authorization Date

07-08-2024

Number Of Sites

8

Number Of Participants

30

Spain

Latest Decision Or Authorization Date

12-08-2024

Number Of Sites

2

Number Of Participants

19

Italy

Latest Decision Or Authorization Date

23-05-2025

Number Of Sites

8

Number Of Participants

61

Germany

Latest Decision Or Authorization Date

09-08-2024

Number Of Sites

2

Number Of Participants

51

Poland

Latest Decision Or Authorization Date

16-06-2025

Number Of Sites

5

Number Of Participants

35

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

Sponsor duties codes: 1,10,11,12,13,2,5,6,7,8; contact Clinicaltrial.Enquiries@parexel.com

Third parties

• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes: 1,10,11,12,13,2,5,6,7,8","organisation_type":"Pharmaceutical company"}