A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors

Phase 1

Recruiting

• Conditions: HR+ Breast Cancer; Triple Negative Breast Cancer (TNBC); CCNE1 Amplified Advanced Solid Tumors; HR+ HER2- Breast Cancer; Ovarian Cancer; Endometrial Cancer; Uterine Carcinosarcoma
• Interventions: Drug: NKT5097 CDK2/CDK4 dual degrader

• Registration Number: NCT07029399
• Lead Sponsor: NiKang Therapeutics, Inc.

Brief Summary

The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include:

* What is the recommended dose for expansion and/or Phase 2

* What medical issues/symptoms do participants experience when taking NKT5097

Detailed Description

This First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of NKT5097, a novel dual protein degrader of CDK2 and CDK4, is split into 3 Parts:

Part 1: Dose Escalation in selected advanced/metastatic non-CNS primary solid tumors will be enrolled based on a projected total of 5 dose levels

Part 2: Food Effect Analysis: Subjects with solid tumors (as noted in Part 1) will be enrolled (by backfilling selected dose cohorts) to evaluate the effect of dosing with food on NKT5097.

Part 3: Tumor-specific Expansion: Subjects may be enrolled (by backfilling selected dose cohorts) into each selected tumor-specific cohort. One or more of these cohorts may be opened at the discretion of the Sponsor in consultation with the DEC

In addition to the above, the study will explore pharmacokinetics, various pharmacodynamic biomarkers, gene mutations, and tumor responses such as PFS and DOR.

Study Timeline

• Study Start: 2025-03-25
• Study First Submitted: 2025-05-28
• Study First Submitted QC: 2025-06-18
• Study First Posted: 2025-06-19
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2027-07-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 205

Inclusion Criteria

• Able to provide written informed consent
• Advanced unresectable or metastatic solid tumor
• Refractory to or unable to tolerate existing therapies (Part 1 & 2 only)
• Measurable or evaluable disease (Part 1 & 2 only)
• Eighteen years of age or older
• ECOG status of 0 or 1
• Adequate organ function
• Patients with female reproductive organs must be surgically sterile, post- menopausal or willing to use effective contraception per protocol
• Patients who are capable of insemination must be willing to use highly effective contraception and to refrain from sperm donation during treatment and for 28 days after the last dose
• Able to swallow oral meds
• Willing to provide tumor tissue

Exclusion Criteria

• Advanced solid tumor that is a candidate for curative treatment
• 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 I or Stage II cancers currently in complete remission
• Not recovered from the effects of prior anticancer therapy
• Clinically significant cardiovascular event, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months
• Known active CNS metastases and/or carcinomatous meningitis
• Active interstitial lung disease requiring treatment
• History of uveitis, retinopathy, or other clinically significant retinal disease
• Major surgery within 30 days of administration of first dose
• Active uncontrolled infectious disease
• Significant liver disease (Child Pugh class B or C)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	NKT5097 CDK2/CDK4 dual degrader	Escalation of orally administered NKT5097
Part 2 Food Effect	NKT5097 CDK2/CDK4 dual degrader	Orally administered NKT5097 with and without meal
Part 3 Expansion	NKT5097 CDK2/CDK4 dual degrader	Expansion of dose levels based upon safety and PK following Part 1 escalation.

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities as Assessed by CTCAE	From enrollment through end of safety monitoring period of 28 days from first dose

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC last) after a single dose and multiple doses from first dose through the last timepoint with quantifiable concentration (Tlast)	Day 1 and Day 15 of Cycle 1 ((Cycle 1 is 28 days)
Maximum concentration (Cmax) when dosed with and without food	Day 1 and Day 2 of Cycle 1 (Cycle 1 is 28 days)
Area under the concentration-time curve (AUC last) when dosed with and without food from dosing through the last timepoint with quantifiable concentration (Tlast)	Day 1 through Day 3 of Cycle 1 (Cycle 1 is 28 days)
Time to maximum plasma concentration (Tmax) after a single dose and multiple doses	Day 1 through Day 3 and Day 15 of Cycle 1 (Cycle 1 is 28 days)
Investigator-assessed ORR by RECIST v1.1	From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Investigator-assessed PFS by RECIST v1.1	From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Duration of Response (DOR)	From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Incidence of adverse events (AEs) as defined by CTCAE Version 5	From enrollment through end of treatment up to 2 years
Maximum concentration Cmax after a single dose and multiple doses	Day 1 and Day 15 of Cycle 1 (Cycle 1 is 28 days)

Trial Locations

Locations (6)

SCRI Florida Cancer Specialists - Sarasota; 🇺🇸 Sarasota, Florida, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

South Texas Accelerated Research Therapeutics (START) Midwest; 🇺🇸 Grand Rapids, Michigan, United States

South Texas Accelerated Research Therapeutics (START) San Antonio; 🇺🇸 San Antonio, Texas, United States

South Texas Accelerated Research Therapeutics (START) Mountain Region; 🇺🇸 West Valley City, Utah, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States