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
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.
• 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
• At least one measurable site of disease by RECIST 1.1 criteria that has not been previously irradiated.
• Fresh or archived primary or metastatic tissue available for submission for correlative analyses
• Negative serum pregnancy test within 28 days prior to commencement of dosing in premenopausal women. Negative urine pregnancy test within 24 hours of starting treatment.
• Able to swallow and retain oral medication and no clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Adequate baseline organ function