This is a Phase 2, non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in 6 cohorts of patients with specific rare cancers who have unresectable locally advanced or metastatic disease, which is resistant or refractory to standard therapy, or for which standard therapy does not exist, or is not considered appropriate, and for which no other experimental treatment options are available.
The study plans to enrol up to 300 patients in total. Eligible patients who have provided their written informed consent for study participation will be assigned to one of 6 cohorts determined by indication: * Cohort 1: Non-clear cell RCC * Cohort 2: Rare head and neck cancer * Cohort 3: Rare skin cancer * Cohort 4: non-colorectal cancers with microsatellite instability (MSI-nonCRC) * Cohort 5: Penile cancer * Cohort 6: POLE exonucleasic domain mutated cancer Between 20 and 50 patients will be enrolled in each cohort, with the exception of the cohort 1 (Non-clear cell RCC) and cohort 3 (Rare skin cancer). Following the amendment 6, up to a maximum of 20 additional patients may be included in the cohort 1 (Non-clear cell RCC) or cohort 3 (Rare skin cancer), within the limit of 300 patients to be included in total, due to potential signals observed in some subsets. The study will use a two-stage Bayesian enrichment design. The first stage treats all patients from the different cohorts with the investigational product and identifies possibly sensitive indications. The second stage will compare outcomes among subsets of patients in the identified cohorts to distinguish between subpopulations of patients who may benefit from the treatment and patients for whom there is no evidence of efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
269
Treatment
Gustave Roussy Cancer Campus
Villejuif, France
Objective response rate
ORR will be assessed per cohort by an IRC according to RECIST v1.1.
Time frame: measured at the first scheduled disease assessment following study treatment initiation (Day 84, ± 7 days)
Progression-free survival
Assessed according to RECIST v1.1
Time frame: From date of inclusion until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Overall survival
Time frame: From date of inclusion until the date of death from any cause, assessed up to 36 months
Best response
Assessed according to RECIST v1.1
Time frame: From inclusion up to 36 months
Response duration
Assessed according to RECIST v1.1
Time frame: from first observation of objective response until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Time to response
Assessed according to RECIST v1.1
Time frame: from inclusion first observation of objective response, assessed up to 36 months
Frequency and severity of adverse events
assessed according to the NCI-CTCAE v4
Time frame: from inclusion until 100 days after last dose of investigational product
Objective response rate in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
ORR will be assessed per cohort by an IRC according to RECIST v1.1.
Time frame: measured at the first scheduled disease assessment following study treatment initiation (Day 84, ± 7 days)
Progression-free survival in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
Assessed according to RECIST v1.1.
Time frame: From date of inclusion until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Overall survival in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
Time frame: From date of inclusion until the date of death from any cause, assessed up to 36 months
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