This is a single center, phase Ib/II study combining an anti-PD-1 antibody and an anti-CTLA-4 antibody with IL-15. It is testing the hypothesis that the addition of nogapendekin alfa inbakicept to nivolumab and ipilimumab will augment the clinical activity of those two drugs.
Histologically or cytologically confirmed, previously untreated or recurrent metastatic NSCLC.
Availability of archival biopsy tissue or willingness to undergo a biopsy prior to C1D1 for biomarker analysis, including PD-L1 by IHC using a CLIA-certified test. Results of the PD-L1 testing are not required for enrollment.
Measurable disease per RECIST 1.1.
At least 18 years of age.
Mixed histology including small cell lung cancer.
classic EGFR mutations
HER2 mutation
ALK fusion
Sequential
Ipilimumab
DrugIpilimumab will be given intravenously at a dose of 1mg/kg.
Nivolumab
DrugNivolumab will be given intravenously at a dose of 360mg.
Nogapendekin alfa inbakicept
DrugNogapendekin alfa inbakicept will be given subcutaneously at the assigned dose level.
Progression-free survival (PFS) (Phase Ib acceptable dose participants and Phase II participants)
PFS is defined as the duration of time from the start date of study treatment to the date of earliest progression or death, whichever occurs first. Patients who neither progress nor die by the data cutoff date will be censored at the last follow up date.
Incidence of dose-limiting toxicities (DLTs) (Phase Ib participants)
DLTs are defined in the protocol.
Adverse event effect rate (All participants)
Defined as the number of study treatment related adverse events (AEs) and discontinuations due to treatment-related AEs. Adverse events will be assessed using the CTCAE v5.0 criteria.
Disease control rate (DCR) (Phase Ib acceptable dose participants and Phase II participants)
DCR is defined as the proportion of patients achieving either a complete response (CR), partial response (PR), or stable disease (SD), according to RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). 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 progressive disease (PD), taking as reference the smallest sum diameters while on study.
Duration of response (DoR) (Phase Ib acceptable dose participants and Phase II participants) (Phase Ib acceptable dose participants and Phase II participants)
DoR is defined as the time from the confirmation of a CR of PR according to RECIST 1.1 until the first date that recurrent or progressive disease is objectively documented or death from any cause. Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Objective response rate (ORR) (Phase Ib acceptable dose participants and Phase II participants)
ORR is defined as the proportion of patients achieving CR or PR measured according to RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
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Washington University School of Medicine
Lead sponsor
ImmunityBio, Inc.
Collaborator
The Foundation for Barnes-Jewish Hospital
Collaborator
