The goal of the Lead-in phase of the study is to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy. The goal of the Expansion phase of the study is to evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib (Doublet) and with palbociclib and sasanlimab (Triplet) in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior therapy.
This is a Phase 2 open-label, multicenter, global study of NKT2152. This study is designed as two phases: a Lead-in phase and an Expansion phase. Patients must be 18 years or older, with advanced or metastatic clear cell renal cell carcinoma (ccRCC). Eligible patients must have progressed or relapsed after at least 1 prior anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) systemic therapy and 1 immune checkpoint inhibitor (ICI) for advanced or metastatic ccRCC alone or in combination. The Lead-in phase is designed as a dose escalation phase to evaluate the safety, efficacy, pharmacokinetics (PK) and determine recommended dose for expansion (RDE) of NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy. The subsequent Expansion phase will evaluate the safety, efficacy, PK at the selected RDE and identify the RP2D for NKT2152 in combination with palbociclib and sasanlimab in advanced or metastatic ccRCC patients who received prior therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Oral HIF2a inhibitor
a cyclin-dependent kinases (CDK) 4 and 6 inhibitor
an immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1; a solution for injection for subcutaneous administration
University of California San Diego
La Jolla, California, United States
Northwestern University - Feinberg School of Medicine
Chicago, Illinois, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan-Rogel Cancer Center
Ann Arbor, Michigan, United States
Nebraska Cancer Specialists
Omaha, Nebraska, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
UT Southwestern Medical Center
Dallas, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 28 days of dosing) in the Lead-in Phase
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
Time frame: 28 days
Objective Response Rate (ORR) determined by the Investigator
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: 1 years
Progression-free survival (PFS)
PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression or death.
Time frame: 2 years
Duration of Response (DOR)
Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first.
Time frame: 1 years
Time to Response (TTR)
TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.
Time frame: 1 years
Overall Survival (OS)
OS defined as the time from the date the participant started study drug to death for any reason.
Time frame: 2 years
Clinical Benefit Rate (CBR)
CBR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) or a stable disease (SD) of 8 weeks or longer based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: 1 years
Number of Participants with Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.
Time frame: 2 years
Maximum observed plasma concentration (Cmax) of NKT2152
Maximum observed plasma concentration (Cmax) of NKT2152
Time frame: 1 years
Time to maximum observed plasma concentration of NKT2152 (Tmax)
Time to maximum observed plasma concentration of NKT2152 (Tmax)
Time frame: 1 years
Observed trough concentration of NKT2152 (Ctrough)
Observed trough concentration of NKT2152 (Ctrough)
Time frame: 1 years
Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)
Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)
Time frame: 1 years
Maximum observed plasma concentration (Cmax) of palbociclib
Maximum observed plasma concentration (Cmax) of palbociclib
Time frame: 1 years
Time to maximum observed plasma concentration of palbociclib (Tmax)
Time to maximum observed plasma concentration of palbociclib (Tmax)
Time frame: 1 years
Observed trough concentration of palbociclib (Ctrough)
Observed trough concentration of palbociclib (Ctrough)
Time frame: 1 years
Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)
Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)
Time frame: 1 years
Observed trough concentration of sasanlimab (Ctrough)
Observed trough concentration of sasanlimab (Ctrough)
Time frame: 1 years
Maximum observed plasma concentration (Cmax) of sasanlimab
Maximum observed plasma concentration (Cmax) of sasanlimab
Time frame: 1 years
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