This is a Phase 1 open-label, study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of memory-like natural killer cells (ML NK) in combination with nivolumab and relatlimab in subjects with advanced and/or metastatic melanoma. There will be two arms to test the variables of ML NK cell source. ML NK cells from an autologous source will be used for Arm 1, and ML NK cells from an allogeneic source will be used for Arm 2. The investigators hypothesize that ML NK cells from either an autologous source or allogeneic source are safe and tolerable in subjects with advanced and/or metastatic melanoma.
Diagnosis of histologically confirmed advanced or metastatic melanoma that has progressed after at least 12 weeks or a minimum of 2 doses of treatment with a standard of care PD1/PDL1 containing therapy (nivolumab, pembrolizumab, atezolizumab, or durvalumab).
Age: ≥18 years of age
Have an Eastern Cooperative Oncology Group Performance Status (ECOG) ≤ 2 at screening Form Arm 1 only: Patients must meet the eligibility criteria to undergo apheresis to obtain autlogous NK cells.
For Arm 2 only: Patient must have an available allogeneic NK cell donor who meets the eligibility criteria.
Active autoimmune disorder requiring immunosuppression (physiologic steroids defined as ≤15mg prednisone or equivalent are acceptable).
Prior history of an immune-related Grade 3 or 4 AE attributed to prior cancer immunotherapy (other than endocrinopathy managed with either replacement therapy or asymptomatic elevation of serum amylase or lipase) that resulted in permanent discontinuation of the prior immunotherapeutic agent.
Patients with Grade ≤2 irAE who have not completely recovered from irAE (i.e. have residual toxicities >Grade 1) related to prior cancer immunotherapy (other than endocrinopathy management with replacement therapy or stable vitiligo). Patients treated with corticosteroids for irAE must demonstrate absence of related signs or symptoms for ≥7 days following discontinuation of corticosteroids.
Leptomeningeal disease, carcinomatous meningitis, or symptomatic CNS metastases. Patients with asymptomatic brain metastasis with no pending intervention needed, or patients with treated CNS disease and stable for at least 4 weeks and off anti-seizure medication and steroids for 7 days prior to initiation of LDC are eligible.
Parallel
Cytokine-induced memory-like natural killer cells
Biological/VaccineCell product processing is performed at the Siteman Cancer Center Biological Therapy Core Facility (BTCF).
Relatilmab
Biological/VaccineStandard of care
Nivolumab
Biological/VaccineStandard of care
For treatment with cells from an autologous source: Incidence and severity of adverse events
-As determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
For treatment with cells from an allogeneic source: Incidence and severity of adverse events
-As determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Objective response rate (ORR)
Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, according to RECIST v1.1. 4 weeks apart. * Complete Response (CR). Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm).Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR). At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Duration of response (DOR)
-Duration of response (DoR), defined as the time from the first occurrence of a documented response after the ML NK cell infusion, to disease progression according to RECIST v1.1 or death.
Progression-free survival (PFS)
* PFS, defined as the time from ML NK cell infusion to the first occurrence of disease progression according to RECIST 1.1 or death from any cause. * Progressive Disease (PD). At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). Appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Disease control rate (DCR)
* Disease control rate (DCR), defined as the percentage of patients who have achieved a complete response, partial response, or stable disease according to RECIST v1.1. * Complete Response (CR). Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (\<1 cm).Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR). At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD). Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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Washington University School of Medicine
Lead sponsor
Melanoma Research Alliance
Collaborator
Rising Tide Foundation
Collaborator
