Ph2 Study NKT2152 with Palbociclib & Sasanlimab in Subjects with Advanced Clear Cell Renal Cell Carcinoma (ccRcc)
- Conditions
- CcRCCClear Cell Renal Cell CarcinomaKidney CancerKidney NeoplasmsRenal CancerRenal NeoplasmsRecurrent Renal Cell CarcinomaMetastatic Renal Cell CarcinomaRefractory Renal Cell CarcinomaAdvanced Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT05935748
- Lead Sponsor
- NiKang Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 172
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lead-in Doublet combination NKT2152 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). Expansion Triplet combination sasanlimab 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. Lead-in Triplet combination sasanlimab 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 Expansion Doublet combination NKT2152 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. Expansion Triplet combination NKT2152 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. Lead-in Triplet combination NKT2152 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 Lead-in Doublet combination palbociclib 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 combination palbociclib 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 Expansion Doublet combination palbociclib 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. Expansion Triplet combination palbociclib 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.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 28 days of dosing) in the Lead-in Phase 28 days DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
Objective Response Rate (ORR) determined by the Investigator 1 years 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 2 years OS defined as the time from the date the participant started study drug to death for any reason.
Maximum observed plasma concentration (Cmax) of palbociclib 1 years Maximum observed plasma concentration (Cmax) of palbociclib
Observed trough concentration of sasanlimab (Ctrough) 1 years Observed trough concentration of sasanlimab (Ctrough)
Clinical Benefit Rate (CBR) 1 years 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.
Number of Participants with Adverse Events 2 years 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 1 years Maximum observed plasma concentration (Cmax) of NKT2152
Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC) 1 years Area under the plasma concentration time curve (AUC0-t) of NKT2152, and accumulation ratio (RAC)
Time to maximum observed plasma concentration of palbociclib (Tmax) 1 years Time to maximum observed plasma concentration of palbociclib (Tmax)
Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC) 1 years Area under the plasma concentration time curve (AUC0-t) of palbociclib, and accumulation ratio (RAC)
Maximum observed plasma concentration (Cmax) of sasanlimab 1 years Maximum observed plasma concentration (Cmax) of sasanlimab
Progression-free survival (PFS) 2 years 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 to Response (TTR) 1 years TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.
Duration of Response (DOR) 1 years 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 to maximum observed plasma concentration of NKT2152 (Tmax) 1 years Time to maximum observed plasma concentration of NKT2152 (Tmax)
Observed trough concentration of NKT2152 (Ctrough) 1 years Observed trough concentration of NKT2152 (Ctrough)
Observed trough concentration of palbociclib (Ctrough) 1 years Observed trough concentration of palbociclib (Ctrough)
Trial Locations
- Locations (8)
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