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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core Facility (BTCF).
Standard of care
Standard of care
Washington University School of Medicine
St Louis, Missouri, United States
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)
Time frame: From start of treatment through end of safety follow-up (estimated to be 15 months)
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)
Time frame: From start of treatment through end of safety follow-up (estimated to be 15 months)
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.
Time frame: Through completion of treatment (estimated to be 12 months)
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.
Time frame: Through completion of follow-up (estimated to be 3 years)
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.
Time frame: Through completion of follow-up (estimated to be 3 years)
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.
Time frame: Through completion of follow-up (estimated to be 3 years)
Overall survival (OS)
-OS, defined as the time from ML NK cell infusion to death from any cause.
Time frame: Through completion of follow-up (estimated to be 3 years)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.