NKT5097 for adults with advanced or metastatic solid tumors.

A Phase 1, First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of the Novel Oral Selective CDK2/CDK4 Dual Degrader NKT5097 in Adults With Advanced/Metastatic Solid Tumors

This trial tests an oral drug called NKT5097 in adults with advanced or metastatic solid tumors—especially certain breast cancers and tumors with CCNE1 amplification—to see if it is safe and shows anti‑tumor activity.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 205 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: NiKang Therapeutics, Inc. (industry)
• Locations: 14 sites (La Jolla, California and 13 other locations)
• Trial ID: NCT07029399 on ClinicalTrials.gov

What this trial studies

This first‑in‑human, open‑label Phase 1 study tests NKT5097, a novel oral dual protein degrader that targets CDK2 and CDK4, in adults with advanced or metastatic non‑CNS solid tumors with emphasis on breast cancer and CCNE1‑amplified tumors. Part 1 uses dose escalation across up to five dose levels to define safety and a recommended dose for expansion, Part 2 examines the effect of food on drug exposure, and Part 3 opens tumor‑specific expansion cohorts by backfilling selected dose levels. The trial will collect pharmacokinetics, pharmacodynamic biomarkers, tumor genomics, safety data, and preliminary anti‑tumor endpoints such as progression‑free survival and duration of response. The open‑label design means investigators and participants know the treatment being administered.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced unresectable or metastatic non‑CNS solid tumors (notably HR+ or triple‑negative breast cancer or CCNE1‑amplified tumors), ECOG 0–1, adequate organ function, measurable disease, refractory to or intolerant of standard therapies, able to swallow oral medication, and willing to provide tumor tissue.

Not a fit: Patients unlikely to benefit include those who are candidates for curative treatment, have poor organ function or ECOG >1, have untreated CNS primary tumors, or cannot take oral medications or comply with study requirements.

Why it matters

Potential benefit: If successful, NKT5097 could offer a new targeted oral treatment that controls or shrinks tumors driven by CDK2/CDK4 activity or CCNE1 amplification, potentially extending progression‑free survival for patients with resistant disease.

How similar studies have performed: While approved CDK4/6 inhibitors have shown benefit in HR+ breast cancer, a first‑in‑human CDK2/CDK4 degrader like NKT5097 is novel and has not yet been proven in humans.

Eligibility criteria

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)

Where this trial is running

La Jolla, California and 13 other locations

• UC San Diego Moores Cancer Center — La Jolla, California, United States (RECRUITING)
• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States (RECRUITING)
• Yale Cancer Center — New Haven, Connecticut, United States (RECRUITING)
• SCRI Florida Cancer Specialists - Sarasota — Sarasota, Florida, United States (RECRUITING)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids, Michigan, United States (RECRUITING)
• Washington University — St Louis, Missouri, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (RECRUITING)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) San Antonio — San Antonio, Texas, United States (RECRUITING)
• South Texas Accelerated Research Therapeutics (START) Mountain Region — West Valley City, Utah, United States (RECRUITING)
• NEXT Virginia — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Sponsor Contact

Conditions: HR+ Breast Cancer, Triple Negative Breast Cancer, CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer, Ovarian Cancer, Endometrial Cancer, Uterine Carcinosarcoma, CCNE1