Unresectable or Advanced Melanoma MedDRA version: 21.1 Level: LLT Classification code 10025655 Term: Malignant melanoma of skin System Organ Class: 100000004864 MedDRA version: 20.0 Level: HLT Classification code 10027156 Term: Skin melanomas (excl ocular) System Organ Class: 100000004858
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Study 4. Patient must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype. 5. Availability of a fresh tumour biopsy taken at screening, if medically feasible as per investigator assessment. If a mandatory fresh biopsy is not feasible, the patient is permitted to enrol if they have an archival sample up to 5 years. 6. Patient must have received at least 1 prior immunotherapy (anti-PD-(L)1 ± anti-CTLA-4) for a minimum of 6 weeks. 7. Patients must have confirmed progression during treatment with a PD-(L)1 inhibitor +/- a CTLA 4 inhibitor, eg, nivolumab, pembrolizumab, or atezolizumab, or the combination of nivolumab and ipilimumab. Confirmed progression is defined as radiologic progression confirmed by a second scan at 4 to 12 weeks after the initial scan showing disease progression or, a single scan showing radiological progression accompanied by correlative symptoms suggestive to disease progression. 14. Measurable disease by RECIST 1.1. At least 1 lesion that can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with CT or MRI and is suitable for accurate repeated measurements. Tumour assessment by CT scan or MRI must be performed within 28 days prior to randomisation. Cutaneous lesions and other superficial lesions are not considered measurable disease lesions, but may be considered as non-target lesions. For patients in the main study: if the patient has only 1 measurable lesion per RECIST 1.1, the biopsy specimen should be obtained from the non-target lesion or archival tissue. Other inclusion criteria per protocol apply Biopsy Sub-Study Patients are eligible to be included in the biopsy sub-study only if they meet all of the inclusion/ exclusion criteria of the main study and all of the following criteria: 1. Consent to the provision of 3 mandatory tumour biopsies. 2. 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. 3. Lesions used for biopsy should be different from those used as RECIST lesions, unless there are no other lesions suitable for biopsy. 4. Lesions used for biopsy may have received prior radiation therapy only if there is documented evidence of progression in the lesion after radiation treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 122 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 123
Exclusion criteria
Exclusion criteria: Main Study 3. 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. 5. Uveal melanoma (eg, choroidal, iris, and ciliary body). 6. 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. Note: Patients with an endocrine AE of Grade = 2 are permitted to enrol if they are stably maintained on appropriate replacement therapy and are asymptomatic. 11 Inadequate bone marrow and impaired hepatic or renal function as demonstrated by any of the following laboratory values: ?Haemoglobin 2.5 x institutional ULN unless liver metastases are present in which case it must be > 5 x ULN. ?Serum creatinine > 1.5 x institutional ULN. ?Glomerular filtration rate < 45 mL/min, as assessed by Cockroft-Gault, MDRD or CKD-EPI formulae, EDTA clearance or 24-hour urine collection. The same method should be used throughout the study for each patient. ?International normalised ratio = 1.5 or other evidence of impaired hepatic synthesis function. Patients on warfarin may participate in this study but it is recommended that their INR is monitored more frequently. Other exclusion criteria per protocol apply Biopsy Sub-Study 1. Patients must comply with the exclusion criteria described for the main study. 2. Patients with evidence of bleeding disease deemed unsafe for serial biopsies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the effectiveness of ceralasertib monotherapy and ceralasertib plus durvalumab by assessment of objective response rate (ORR) in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor.;Secondary Objective: To estimate the effectiveness of ceralasertib monotherapy and ceralasertib plus durvalumab by assessment of: ?Duration of Response (DoR) in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor. ?Time to objective response (TTR) in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor. ?Change in target lesion (TL) tumour size in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor. ?Progression free survival (PFS) in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor. ?Overall survival (OS) in patients with unresectable or advanced melanoma and primary or secondary resistance to a PD-(L)1 inhibitor.;Primary end point(s): Main Study: ?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. Biopsy Sub-study: ?CD8+ T cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies.;Timepoint(s) of evaluation of this end point: Main Study: ?Throughout the study. Biopsy Sub-study: ?Baseline. ?On-treatment tumour biopsies. ?Off-treatment tumour biopsies. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main Study: ?Median and landmark DoR estimates at 6, 9, 12, 15, and 18 months. ?Median TTR and proportion of patients with response at the first scheduled tumour assessment. ?Percentage change from baseline in TL tumour size at week 16 and best percentage change from baseline. ?Median and landmark PFS at 3, 6, 9, 12 months, and the hazard ratio comparing the 2 treatment arms. ?Median and landmark OS at 6, 9, 12, and 18 months, and the hazard ratio comparing the 2 treatment arms. Biopsy Sub-study: ?As described for the main study, using the investigator assessment of tumour response per RECIST 1.1 ?Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50.;Timepoint(s) of evaluation of this end point: Main study: ?At 6, 9, 12, 15, 18 months. ?First scheduled tumour assessment. ?Week 16 from baseline. ?3, 6, 9, 12 months. ?At 6, 9, 12, 18 months. Biopsy Sub-study: ?At 6, 9, 12, 15, 18 months. First scheduled tumour assessment. Week 16 from baseline. 3, 6, 9, 12 months. At 6, 9, 12, 18 months. ?Pre-Treatment. On-treatment. Off-treatment. | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed