ctDNA-guided Addition of Ipilimumab to Patients Receiving Nivolumab and Relatlimab
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNYU Langone Health
About this trial
The purpose of this study is to investigate the use of ctDNA measurements to guide first-lien therapy choice for patients with advanced or metastatic melanoma. Primary endpoints include progression-free survival. Secondary study endpoints include objective response rate and incidence and severity of immune-related adverse events.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient must be ≥ 18 years old.
Patients must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent from (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
Patients must be willing and able to comply with scheduled visits, laboratory tests, and other requirements of the study.
Patient must have active advanced melanoma, defined as unresectable stage IIIB-IV by American Joint Committee on Cancer (AJCC) 8th edition. Patients with mucosal melanoma defined as unresectable stage III or regional/distant metastatic disease are eligible.
Disqualifiers
Patients with carcinomatosis meningitis or a history of current ocular/uveal melanoma are excluded.
Patients with a history of myocarditis.
Patients with active, known, or suspected autoimmune disease requiring immunosuppression beyond 10 mg daily of prednisone. Patients with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the Principal Investigator be consulted prior to signing informed consent.
Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of C1D1. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
Trial design
Design model
Parallel
Treatments tested in this trial
Nivolumab
Drug480 mg Nivolumab every 4 weeks
Relatlimab
Drug160 mg Relatlimab every 4 weeks
Ipilimumab
Drug50 mg (1 mg/kg) intravenously every 8 weeks
Signatera genome MRD assay
DeviceSignateraTM is a personalized, tumor-informed circulating tumor DNA (ctDNA)-based test of molecular residual disease (MRD). The Signatera Designed on Genome test is a qualitative and quantitative test that reports the presence or absence of ctDNA as "ctDNA Positive" or "ctDNA Not Detected".
Treatment groups
90 Participants
are divided into 4 treatment groupsGroup A: Cohort A: Undetectable ctDNAExperimental treatment 3 interventions
Group B: Cohort B: Positive ctDNA without early progresson (continue treatment)Active comparator 3 interventions
Group C: Cohort B: Positive ctDNA without early progression (switch treatment)Experimental treatment 4 interventions
Group D: Cohort C: Positive ctDNA with early progressionExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Progression Free Survival rate in patients randomized in Cohort B
Progression-free survival (PFS), defined as the time from first treatment administration until progressive disease (PD) according to RECIST v1.1 (with irRECIST used as a supportive criterion) or death from any cause, whichever occurs earlier.
Time frame
Month 6Secondary outcomes
1
Objective response rate (CR+PR)
Objective response rate (ORR) (CR+PR) by RECIST 1.1, with irRECIST supportive, reported as the percentage of patients achieving response in all cohorts. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. The ORR is the response recorded from the start of the treatment until month 6
Time frame
Month 62
Incidence of immune-related adverse events (irAEs) with ipilimumab, relatlimab, and nivolumab triplet therapy administered after prior nivolumab plus relatlimab doublet therapy.
From the first treatment administration until final on-treatment visit.
Time frame
Up to 2 years3
Progression-free survival in Cohorts A and C
Progression-free survival (PFS), defined as the time from first treatment administration until progressive disease (PD) according to RECIST v1.1 (with irRECIST used as a supportive criterion) or death from any cause, whichever occurs earlier.
Time frame
Month 64
Progression-free survival
Progression-free survival (PFS), defined as the time from first treatment administration until progressive disease (PD) according to RECIST v1.1 (with irRECIST used as a supportive criterion) or death from any cause, whichever occurs earlier.
Time frame
Month 12Sponsors and contacts
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Source ClinicalTrials.gov