A Study of NKT2152, a HIF2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma

NCT ID: NCT05119335

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-26
• Study Completion Date: 2025-09-30

Brief Summary

The goal of the Phase 1 portion is to identify the maximum tolerated dose (MTD) and/or the recommended doses for expansion (RDEs) of NKT2152. The Phase 2 portion will evaluate the efficacy of NKT2152 in ccRCC.

Detailed Description

This is a Phase 1/2 open label multicenter study of NKT2152. Phase 1 is a first in human (FIH) dose escalation study in patients aged 18 years or older with clear cell renal carcinoma (ccRCC) who have exhausted available standard therapy as determined by the investigator.

Phase 1 is designed to determine the MTD and/or RDEs of NKT2152 as a single agent administered orally once daily. Depending on the tolerability and PK, additional dosing schedules may be tested. Phase 2 will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 in ccRCC patients. Patients will be randomized to one of two dosage levels selected for further evaluation.

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; Hypoxia; Renal Cell Carcinoma; Hypoxia Inducible Factor (HIF); HIF2α Inhibitor; Hypoxia Inducible Factor 2 Alpha (HIF-2 Alpha); Hypoxia Inducible Factor 2α (HIF-2α); Clear Cell

Keywords

Hypoxia inducible factor (HIF); HIF2α INHIBITOR; HIF1α; clear cell; Hypoxia inducible factor 2 alpha (HIF-2 alpha); Hypoxia inducible factor 2α (HIF-2α); Renal Cell Carcinoma (RCC); Kidney Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 dose escalation

Phase 1 is designed to determine the maximum tolerated dose and/or identify the recommended Phase 2 dose of NKT2152 as a single agent administered orally once daily in ccRCC patients

Group Type: EXPERIMENTAL

Oral NKT2152

Intervention Type: DRUG

Oral HIF2α inhibitor

Phase 2 dose expansion

Phase 2 dose expansion will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 as a single agent administered orally once daily in ccRCC patients. Patients will be randomized to one of two dosage levels being evaluated.

Group Type: EXPERIMENTAL

Oral NKT2152

Intervention Type: DRUG

Oral HIF2α inhibitor

Interventions

Oral NKT2152

Oral HIF2α inhibitor

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Known symptomatic brain metastases requiring > 10 mg/day of prednisone (or its equivalent). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of NKT2152 treatment, fulfill the above steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after CNS-directed treatment.

2. Having one or more of the following conditions:

1. A pulse oximetry reading less than 95% at screening;

2. Any current requirement for intermittent or chronic supplemental oxygen;

3. Any chronic lung condition which has required supplemental oxygen in the past;

4. Evidence of impending airway compromise (such as endobronchial tumor, lymphangitic spread, significant extrinsic compression of major airway) per investigator;

5. Ascites requiring drainage within 28 days prior to W1D1

3. History of another malignancy except for the following: adequately treated local basal cell or squamous carcinoma of the skin, in situ cervical cancer, adequately treated papillary noninvasive bladder cancer, other adequately treated Stage 1 or Stage 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years

4. Has failed to recover from the effects of prior anticancer therapy to baseline level or Grade 1 severity (except for alopecia) per NCI CTCAE; patients with treatable adverse effects such as hypothyroidism or hypertension may be enrolled if the adverse effect is controlled with treatment

5. Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of NKT2152 treatment; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy, symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; ≥ Grade 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥160 mmHg) despite adequate use of anti-hypertensives; or history of congenital prolonged QT syndrome or repeated demonstration of a QTc interval > 480 ms; ejection fraction < 40%; clinically significant pericardial or pleural effusion in the opinion of the investigator.

6. Has received prior investigational therapy or standard therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter

7. Has a bleeding diathesis or coagulopathy

8. Deep vein thrombosis (DVT)/pulmonary embolism are allowed as long as patient is not symptomatic and received 2 weeks or more of adequate anticoagulation

9. Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease

10. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results

11. Has had major surgery within 4 weeks before first study drug administration; the following procedures are not considered to be major surgeries: thoracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy, endoscopic or ultrasonographic procedures, mediastinoscopy, skin biopsy, incisional biopsy, image-guided biopsy for diagnostic purposes, and routine dental procedures

12. Has known human immunodeficiency virus (HIV)

13. Has an active infection requiring systemic treatment

14. Is actively participating in another therapeutic clinical trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NiKang Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

HonorHealth

Scottsdale, Arizona, United States

UCLA

Los Angeles, California, United States

Sarah Cannon Research Institute

Denver, Colorado, United States

Emory University

Atlanta, Georgia, United States

Indiana University Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

National Cancer Institute

Bethesda, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Other Identifiers

NKT2152-101

Identifier Type: -

Identifier Source: org_study_id