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
Interventions
Product Name: Infliximab
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: INFLIXIMAB
Current Sponsor code: NA
Concentration unit: mg milligr
Sponsors
ASTRAZENECA AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Study - Patient must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype. - 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. - Patient must have received at least 1 prior immunotherapy (anti-PD( L)1 ± anti-CTLA-4) for a minimum of 6 weeks. - 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. - 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 nontarget 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. PLEASE, REFER TO THE PROTOCOL FOR FURTHER INCLUSION CRITERIA 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 - 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. - Uveal melanoma (eg, choroidal, iris, and ciliary body). - 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 = 1.5 × the ULN or >= 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia). - Aspartate aminotransferase/transaminase (SGOT)/Alanine aminotransferase/transaminase (ALT) (SGPT) > 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 = 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 PLEASE, REFER TO THE PROTOCOL FOR FURTHER EXCLUSION CRITERIA
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.;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. PLEASE REFER TO THE PROTOCOL FOR FURTHER DETAILS | — |
Countries
Australia, Belgium, Canada, France, Germany, Italy, Korea, Democratic People's Republic of, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed