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

Sponsor

NiKang Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05119335

Collaborator

(none)

Enrollment

Locations

Arms

58.2

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

98 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Phase 1 dose escalation and Phase 2 dose expansionPhase 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 :

Oct 26, 2021

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 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

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

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) [21 days]
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
Recommended Phase 2 Dose (RP2D) Determined in the Dose Escalation Phase (Phase 1) [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.
Objective Response Rate (ORR) determined by the Investigator in the Dose Expansion Phase (Phase 2) [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

Number of Participants with Adverse Events [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.
Area under the plasma concentration time curve (AUC0-t) of NKT2152 [Up to Day 22]
Area under the plasma concentration time curve (AUC0-t) of NKT2152.
Area under the plasma concentration time curve (AUC0-∞) of NKT2152 [Up to Day 22]
Area under the plasma concentration time curve (AUC0-∞) of NKT2152
Maximum observed plasma concentration (Cmax) of NKT2152 [Up to Day 22]
Maximum observed plasma concentration (Cmax) of NKT2152
Time to maximum observed plasma concentration of NKT2152 (Tmax) [Up to Day 22]
Time to maximum observed plasma concentration of NKT2152 (Tmax)
Objective Response Rate (ORR) determined by the Investigator in the Dose Escalation Phase (Phase 1) [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.
Duration of response (DOR) [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.
Disease control rate (DCR) determined by the Investigator [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.
Progression free survival (PFS) [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.
Overall survival (OS) [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth	Scottsdale	Arizona	United States	85258
2	Sarah Cannon Research Institute	Denver	Colorado	United States	80218
3	Indiana University Simon Comprehensive Cancer Center	Indianapolis	Indiana	United States	46202
4	National Cancer Institute	Bethesda	Maryland	United States	20892-9760
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
7	MD Anderson Cancer Center	Houston	Texas	United States	77030