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

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.

Study Overview

• Status: Terminated
• Conditions: Neoplasms; Kidney Cancer; Kidney Neoplasms; Carcinoma, Renal Cell; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Clear Cell Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Renal Cancer; Advanced Renal Cell Carcinoma; Renal Neoplasms; ccRCC; Refractory Renal Cell Carcinoma; Neoplasm by Histology
• Intervention / Treatment: Drug: NKT2152; Drug: palbociclib; Other: sasanlimab

Detailed Description

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
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University Of California San Diego
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University - Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan-Rogel Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists
  • New York
    • New York, New York, United States, 10065-6094
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390-9324
      • UT Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have locally advanced or metastatic ccRCC and have progressed or relapsed after at least 1 prior anti-VEGF/VEGFR systemic therapy and 1 ICI.
• Measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• KPS score of at least 70%
• Able to swallow oral medications.

Exclusion Criteria:

• Active CNS metastases and/or carcinomatous meningitis
• Has had any major cardiovascular event within 6 months or clinically significant cardiovascular disease
• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 3 months before administration of study drug.
• Has known HIV
• History of hepatitis B or known active hepatitis C infection
• Has received prior treatment with NKT2152, other HIF2α inhibitors, other CDK 4/6 inhibitors, palbociclib, or sasanlimab
• Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before administration of the first dose of study treatment
• Corrected QT interval calculated by Fridericia formula (QTcF) > 480 ms within 28 days prior to first dose
• Hypoxia or requires intermittent or chronic supplemental oxygen or any chronic lung condition which has required supplemental oxygen in the past
• Has a history of interstitial lung disease
• Has any active or recent history of a known or suspected autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lead-in Doublet combination; 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).	Drug: NKT2152; Oral HIF2a inhibitor; Drug: palbociclib; a cyclin-dependent kinases (CDK) 4 and 6 inhibitor; Other Names: IBRANCE®
Experimental: Lead-in Triplet combination; 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	Drug: NKT2152; Oral HIF2a inhibitor; Drug: palbociclib; a cyclin-dependent kinases (CDK) 4 and 6 inhibitor; Other Names: IBRANCE®; Other: sasanlimab; an immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1; a solution for injection for subcutaneous administration
Experimental: Expansion Doublet combination; 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.	Drug: NKT2152; Oral HIF2a inhibitor; Drug: palbociclib; a cyclin-dependent kinases (CDK) 4 and 6 inhibitor; Other Names: IBRANCE®
Experimental: Expansion Triplet combination; 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.	Drug: NKT2152; Oral HIF2a inhibitor; Drug: palbociclib; a cyclin-dependent kinases (CDK) 4 and 6 inhibitor; Other Names: IBRANCE®; Other: sasanlimab; an immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1; a solution for injection for subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	1 years
Overall Survival (OS)	OS defined as the time from the date the participant started study drug to death for any reason.	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.	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.	2 years
Maximum observed plasma concentration (Cmax) of NKT2152	Maximum observed plasma concentration (Cmax) of NKT2152	1 years
Time to maximum observed plasma concentration of NKT2152 (Tmax)	Time to maximum observed plasma concentration of NKT2152 (Tmax)	1 years
Observed trough concentration of NKT2152 (Ctrough)	Observed trough concentration of NKT2152 (Ctrough)	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)	1 years
Maximum observed plasma concentration (Cmax) of palbociclib	Maximum observed plasma concentration (Cmax) of palbociclib	1 years
Time to maximum observed plasma concentration of palbociclib (Tmax)	Time to maximum observed plasma concentration of palbociclib (Tmax)	1 years
Observed trough concentration of palbociclib (Ctrough)	Observed trough concentration of palbociclib (Ctrough)	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)	1 years
Observed trough concentration of sasanlimab (Ctrough)	Observed trough concentration of sasanlimab (Ctrough)	1 years
Maximum observed plasma concentration (Cmax) of sasanlimab	Maximum observed plasma concentration (Cmax) of sasanlimab	1 years

Collaborators and Investigators

• Sponsor: NiKang Therapeutics, Inc.
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: PD-1; immune checkpoint inhibitors; CDK4 inhibitor; HIF2a; Hypoxia-inducible factor 2alpha; CDK6 inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Urologic Diseases; Carcinoma, Renal Cell; Adenocarcinoma; Urologic Neoplasms; Neoplasms, Glandular and Epithelial; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; palbociclib
• Other Study ID Numbers: NKT2152-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD are not planned to be shared at this time

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No