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

• ClinicalTrials.gov Identifier: NCT05119335
• Recruitment Status: Recruiting
• First Posted: November 15, 2021
• Last Update Posted: October 19, 2022
• Sponsor: NiKang Therapeutics, Inc.
• Information provided by (Responsible Party): NiKang Therapeutics, Inc.

Study Description

Brief Summary:

The goal of the Phase 1 portion is to identify the maximum tolerated dose (MTD) and/or the recommended Phase 2 Dose (RP2D) of NKT2152. The Phase 2 portion will evaluate the efficacy of NKT2152 in ccRCC.

Condition or disease	Intervention/treatment	Phase
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	Drug: Oral NKT2152	Phase 1; Phase 2

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. Eligible patients will have received <=4 prior lines lines of therapy.

Phase 1 is designed to determine the MTD and/or RP2D 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 98 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Phase 1 dose escalation and Phase 2 dose expansion
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open Label Dose-escalation and Expansion Trial of NKT2152, an Orally Administered HIF2α Inhibitor, to Investigate Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity in Patients With Advanced Clear Cell Renal Cell Carcinoma
• Actual Study Start Date: October 26, 2021
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: September 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: Oral NKT2152; Oral HIF2α inhibitor
Experimental: Phase 2 dose expansion; Phase 2 will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 as a single agent administered orally once daily in ccRCC patients	Drug: Oral NKT2152; Oral HIF2α inhibitor

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 21 days of dosing) in the Dose Escalation Phase (Phase 1) [ Time Frame: 21 days ]
   DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
2. Recommended Phase 2 Dose (RP2D) Determined in the Dose Escalation Phase (Phase 1) [ Time Frame: Approximately 2 years ]
   The RP2D will be determined based on observed dose-limiting toxicities (DLTs) and using the totality of PK and biological data in Phase 1.
3. Objective Response Rate (ORR) determined by the Investigator in the Dose Expansion Phase (Phase 2) [ Time Frame: Approximately 1 year ]
   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 :

1. Number of Participants with Adverse Events [ Time Frame: Approximately 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.
2. Area under the plasma concentration time curve (AUC0-t) of NKT2152 [ Time Frame: Up to Day 22 ]
   Area under the plasma concentration time curve (AUC0-t) of NKT2152.
3. Area under the plasma concentration time curve (AUC0-∞) of NKT2152 [ Time Frame: Up to Day 22 ]
   Area under the plasma concentration time curve (AUC0-∞) of NKT2152
4. Maximum observed plasma concentration (Cmax) of NKT2152 [ Time Frame: Up to Day 22 ]
   Maximum observed plasma concentration (Cmax) of NKT2152
5. Time to maximum observed plasma concentration of NKT2152 (Tmax) [ Time Frame: Up to Day 22 ]
   Time to maximum observed plasma concentration of NKT2152 (Tmax)
6. Objective Response Rate (ORR) determined by the Investigator in the Dose Escalation Phase (Phase 1) [ Time Frame: Approximately 1 year ]
   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.
7. Duration of response (DOR) [ Time Frame: Approximately 1 year ]
   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.
8. Disease control rate (DCR) determined by the Investigator [ Time Frame: Approximately 1 year ]
   DCR 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.
9. Progression free survival (PFS) [ Time Frame: Through study completion, an average of 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.
10. Overall survival (OS) [ Time Frame: Through study completion, an average of 2 years ]
    OS defined as the time from the date the participant started study drug to death for any reason.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Has the ability to understand and willingness to sign a written informed consent form before the performance of any study procedures
• Has locally advanced or metastatic ccRCC and has progressed during treatment, are relapsed, refractory and not amenable to curative therapy or standard therapy (Phase 1); has progressed during treatment with at least 1 prior therapeutic regimen (Phase 2) that contains a PD-1 or PD-L1 compound and/or a VEGF targeting agent, and a total of ≤ 4 prior therapeutic regimens.
• Must have measurable disease per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Is of age ≥ 18 years
• Has an Eastern Cooperative Oncology Group performance status of 0-2
• Has a life expectancy of ≥ 3 months
• Has adequate organ function

Exclusion Criteria:

• 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.
• Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
• 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
• Has failed to recover from the effects of prior anticancer therapy to baseline level or grade 1 severity (except for alopecia) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE); patients with treatable adverse effects such as hypothyroidism or hypertension may be enrolled if the adverse effect is controlled with treatment
• 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
• Has received prior treatment with a HIF2α inhibitor

Contacts and Locations

Contacts

Contact: Sponsor Contact; (302) 415-5127; clinicaltrials@nikangtx.com

Locations

United States, Arizona

HonorHealth; Recruiting

Scottsdale, Arizona, United States, 85258

Principal Investigator: Michael Gordon, MD

United States, Colorado

Sarah Cannon Research Institute; Recruiting

Denver, Colorado, United States, 80218

Principal Investigator: Gerald Falchook, MD

United States, Indiana

Indiana University Simon Comprehensive Cancer Center; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Theodore Logan, MD

Principal Investigator: Theodore Logan, MD

United States, Maryland

National Cancer Institute; Not yet recruiting

Bethesda, Maryland, United States, 20892-9760

Contact: Ram Srinivasan, MD

Principal Investigator: Ram Srinivasan, MD

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Toni Choueiri, MD

United States, Nebraska

Nebraska Cancer Specialists; Recruiting

Omaha, Nebraska, United States, 68130

Contact: Ralph Hauke, MD 402-334-4773 rhauke@nebraskacancer.com

Principal Investigator: Ralph Hauke, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Eric Jonasch, MD

Sponsors and Collaborators

NiKang Therapeutics, Inc.

More Information

• Responsible Party: NiKang Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05119335
• Other Study ID Numbers: NKT2152-101
• First Posted: November 15, 2021
• Last Update Posted: October 19, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: IPD are not planned to be shared at this time

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NiKang Therapeutics, Inc.:

HIF2α; NKT2152

Additional relevant MeSH terms:

Carcinoma; Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases