Advanced (unresectable or metastatic) melanoma
Conditions
Interventions
The medicinal interventions include nivolumab/ipilimumab combination therapy.
All of these compounds will be supplied by the sponsor. In part 1,
Nivolumab/ipilimumab combination therapy (Arm A and B
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Adult subjects (>=18 years) with histologically confirmed unresectable Stage III or Stage IV Melanoma as per AJCC staging system.;-Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;-No prior systemic anticancer therapy for unresectable or metastatic melanoma. Prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to date of first dose, and all related adverse events have either returned to baseline or stabilized.;-Measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) criteria;-Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. In order to be randomized, a subject must be classified as PD-L1 positive, PD-L1 negative, or PD-L1 indeterminate. If an insufficient amount of tumor tissue from an unresectable or metastatic site is available prior to the start of the screening phase, subjects must consent to allow the acquisition of additional tumor tissue for performance of biomarker analyses.;-Known BRAF V600 mutation status as determined by local institutional standard or subject to consent to BRAF V600 mutation testing per local institutional standards during the Screening Period, the results of which must be reported within 3 months of randomization. All BRAF statuses (BRAF wild-type or BRAF 600 mutation positive) are eligible.
Exclusion criteria
Exclusion criteria: - Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no evidence of progression via magnetic resonance imaging (MRI, except where contraindicated in which CT scan is acceptable) for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for high doses of systemic corticosteroids that could result in immunosuppression (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.;-Ocular melanoma;-Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol;ADDITIONAL FOR PET TRACER SUB STUDY: Additional exclusion criteria for PET imaging. Subjects with the following condition(s) may be considered for participation in the study but will not undergo the PD-L1 PET imaging: - Subjects who cannot tolerate an imaging procedure. - Subjects who have received therapeutic radiopharmaceutical within 7 days prior to participation in this study. - Subjects with history of IV drug use which would prevent venous access for PET tracer injection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is the incidence of drug-related Grade 3 - 5 AE*s. | — |
Secondary
| Measure | Time frame |
|---|---|
| The first secondary endpoint is objective response rate (ORR) as determined by investigators. The ORR is defined as the number of subjects with a Best overall response (BOR) of complete response (CR) or Partial response (PR) divided by the number of treated subjects for each treatment group. The second secondary endpoint is Progression free survival (PFS) defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death. The third secondary endpoint is Overall survival (OS) defined as the time between the date of randomization and the date of death due to any cause. The fourth secondary objective (to evaluate HRQoL) will be measured by mean changes from baseline in the EORTC-QLQ-30 global health status/QoL composite scale and by mean changes from baseline in the remaining EORTC QLQ-30 scales. | — |
Countries
Netherlands
Outcome results
None listed