Clinical trial NCT05935748: Ph2 Study NKT2152 with Palbociclib & Sasanlimab in Subjects with Advanced Clear Cell Renal Cell Carcinoma (ccRcc)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: CcRCC
Clear Cell Renal Cell Carcinoma
Kidney Cancer
Kidney Neoplasms
Renal Cancer
Renal Neoplasms
Recurrent Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Refractory Renal Cell Carcinoma
Advanced Renal Cell Carcinoma
Carcinoma
Neoplasms
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasm by Histology
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Keywords: HIF2a
Hypoxia-inducible factor 2alpha
CDK4 inhibitor
CDK6 inhibitor
PD-1
immune checkpoint inhibitors
Lead sponsor: NiKang Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2023-07-07
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Lead-in/Dose Escalation (doublet \& triplet combination) and Dose Expansion (doublet \& triplet combination)
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 28 days of dosing) in the Lead-in Phase
timeFrame: 28 days
measure: Objective Response Rate (ORR) determined by the Investigator
timeFrame: 1 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Duration of Response (DOR)
timeFrame: 1 years
measure: Time to Response (TTR)
timeFrame: 1 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Clinical Benefit Rate (CBR)
timeFrame: 1 years
measure: Number of Participants with Adverse Events
timeFrame: 2 years
measure: Maximum observed plasma concentration (Cmax) of NKT2152
timeFrame: 1 years
measure: Time to maximum observed plasma concentration of NKT2152 (Tmax)
timeFrame: 1 years
measure: Observed trough concentration of NKT2152 (Ctrough)
timeFrame: 1 years
measure: Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)
timeFrame: 1 years
measure: Maximum observed plasma concentration (Cmax) of palbociclib
timeFrame: 1 years
measure: Time to maximum observed plasma concentration of palbociclib (Tmax)
timeFrame: 1 years
measure: Observed trough concentration of palbociclib (Ctrough)
timeFrame: 1 years
measure: Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)
timeFrame: 1 years
measure: Observed trough concentration of sasanlimab (Ctrough)
timeFrame: 1 years
measure: Maximum observed plasma concentration (Cmax) of sasanlimab
timeFrame: 1 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan-Rogel Cancer Center
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
References: