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Palbociclib

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Lead-in Doublet assesses safety of oral dosing NKT2152 at increasing dosage levels in combination with palbociclib to determine a recommended dose for expansion (RDE).

Lead-in Triplet assesses the safety of two doses of NKT2152 identified in the Doublet arm (RDE and RDE-1) by orally dosing ccRCC patients with NKT2152 in combination with palbociclib and sasanlimab

Subjects randomized to Arm 1 will receive the Doublet combination (NKT2152 in combination with palbociclib) to provide an assessment of anti-tumor activity and to determine the RP2D.

Subjects randomized to Arm 2 will receive the Triplet therapy (NKT2152 in combination with palbociclib and sasanlimab) to provide an assessment of anti-tumor activity and to determine the RP2D.

NKT2152

a cyclin-dependent kinases (CDK) 4 and 6 inhibitor

palbociclib

an immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1; a solution for injection for subcutaneous administration

sasanlimab

Joanna Dojillo, M.Sc.

Sponsor Contact

Katie O'Neil

Rana McKay, MD

Rachel Springdorf

Ashley Matza-Wambaja

David VanderWelle, MD

Elena Stratis

Meredith Flynn

Toni Choueiri, MD

Cherie Donze

Ulka Vaishmpayan, MD

Tiffiny Bradley

Hanna Kurz

Ralphe Hauke, MD

Jodi-Ann Powell

Martin Voss, MD

Amy Rowell

Andrea Flaten

Hans Hammers

Sydney Sanders

Alexandra Cash

Robert Dreicer, MD

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.

Lead-in/Dose Escalation (doublet \& triplet combination) and Dose Expansion (doublet \& triplet combination)

Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc)

A Phase 2 Trial to Evaluate the Safety and Efficacy of NKT2152 in Combination With Palbociclib (Doublet) and With Palbociclib and Sasanlimab (Triplet) in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

IPD are not planned to be shared at this time

DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.

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.

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.

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.

TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.

OS defined as the time from the date the participant started study drug to death for any reason.

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.

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.

Maximum observed plasma concentration (Cmax) of NKT2152

Time to maximum observed plasma concentration of NKT2152 (Tmax)

Observed trough concentration of NKT2152 (Ctrough)

Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)

Maximum observed plasma concentration (Cmax) of palbociclib

Time to maximum observed plasma concentration of palbociclib (Tmax)

Observed trough concentration of palbociclib (Ctrough)

Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)

Observed trough concentration of sasanlimab (Ctrough)

Maximum observed plasma concentration (Cmax) of sasanlimab

Spots Global Cancer Trial Database for cdk6 inhibitor