LIMIT Melanoma: (Lysosomal Inhibition + Melanoma ImmunoTherapy) A Phase 1/2 Open Label Trial of Nivolumab and Hydroxychloroquine or Nivolumab/Ipilimumab and Hydroxychloroquine in Patients With Advanced Melanoma
Ravi Amaravadi, MD
Summary
This study will evaluate the safety, tolerability and efficacy (objective response rate) of using hydroxychloroquine (HCQ) in combination with nivolumab and ipilimumab or with nivolumab alone in subjects with advanced/metastatic melanoma.
Description
There are three parts to this Phase 1/2 study in subjects with advanced melanoma: Phase 1a will identify the MTD and preliminary safety of combination hydroxychloroquine and nivolumab therapy. Phase 1b will identify the MTD and preliminary safety of hydroxychloroquine administered in conjunction with nivolumab and ipilimumab therapy Phase 2 will assess the clinical efficacy of combination hydroxychloroquine and nivolumab therapy.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histological or cytological evidence of melanoma, unresectable Stage III or Stage IV, any genotype, and any programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status * Phase 1a: nivolumab + HCQ: any prior treatment, or treatment naïve * Phase 2: nivolumab + HCQ: * \- - Cohort 2a: prior immunotherapy in the adjuvant or metastatic setting is required * \- - Cohort 2b: anti-PD-1 Ab-naïve, but may have received any prior other therapy * Phase 1b nivolumab + ipilimumab + HCQ: anti-PD-1 refractory * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1…
Interventions
- DrugNivolumab
Combination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab
- DrugHydroxychloroquine
Combination of nivolumab and hydroxychloroquine OR nivolumab, hydroxychloroquine and ipilimumab
- DrugIpilimumab
Combination of nivolumab, hydroxychloroquine and ipilimumab
Location
- Abramson Cancer Center at University of PennsylvaniaPhiladelphia, Pennsylvania