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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05935748
• Other study ID #: NKT2152-202
• Status: Recruiting
• Phase: Phase 2
• Start date: July 28, 2023
• Est. completion date: September 2026

Study information

• Verified date: December 2023
• Source: NiKang Therapeutics, Inc.
• Contact: Joanna Dojillo, M.Sc.
• Phone: 3024155127
• Email: clinicaltrials[@]nikangtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: September 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 HIF2a 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell
• ccRCC
• Clear Cell Renal Cell Carcinoma
• Kidney Cancer
• Kidney Diseases
• Kidney Neoplasms
• Metastatic Renal Cell Carcinoma
• Neoplasm by Histology
• Neoplasms
• Neoplasms by Site
• Neoplasms, Glandular and Epithelial
• Recurrent Renal Cell Carcinoma
• Refractory Renal Cell Carcinoma
• Renal Cancer
• Renal Neoplasms
• Urogenital Neoplasms
• Urologic Diseases
• Urologic Neoplasms

Intervention

Drug:
• NKT2152
Oral HIF2a inhibitor
• palbociclib
a cyclin-dependent kinases (CDK) 4 and 6 inhibitor

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

Locations

Country	Name	City	State
United States	University of Michigan-Rogel Cancer Center	Ann Arbor	Michigan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern University - Feinberg School of Medicine	Chicago	Illinois
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of California San Diego	La Jolla	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Nebraska Cancer Specialists	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
NiKang Therapeutics, Inc.	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

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