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

NiKang Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Neoplasm by Histology; CcRCC; Carcinoma, Renal Cell; Metastatic Renal Cell Carcinoma; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Renal Neoplasms; Clear Cell Renal Cell Carcinoma; Urologic Diseases; Kidney Diseases; Neoplasms; Refractory Renal Cell Carcinoma; Urogenital Neoplasms; Renal Cancer; Advanced Renal Cell Carcinoma; Kidney Neoplasms; Kidney Cancer; Recurrent Renal Cell Carcinoma; Urologic Neoplasms

Treatments: Drug: NKT2152; Drug: palbociclib; Other: sasanlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05935748

NKT2152-202

Details and patient eligibility

About

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.

Full 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.

Enrollment: 172 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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172 participants in 4 patient groups

Lead-in Doublet combination

Experimental group

Description:

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).

Treatment:

Drug: palbociclib

Drug: NKT2152

Lead-in Triplet combination

Experimental group

Description:

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

Treatment:

Other: sasanlimab

Drug: palbociclib

Drug: NKT2152

Expansion Doublet combination

Experimental group

Description:

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.

Treatment:

Drug: palbociclib

Drug: NKT2152

Expansion Triplet combination

Experimental group

Description:

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.

Treatment:

Other: sasanlimab

Drug: palbociclib

Drug: NKT2152