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Evaluating NKT3964 for Adults with Advanced 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 CDK2 Degrader NKT3964 in Adults With Advanced/Metastatic Solid Tumors

Phase 1 Interventional NiKang Therapeutics, Inc. · NCT06586957

This study is testing a new drug called NKT3964 to see if it can safely help adults with advanced solid tumors, like ovarian or triple-negative breast cancer, after other treatments have failed.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment150 (estimated)
Ages18 Years and up
SexAll
SponsorNiKang Therapeutics, Inc. Industry-sponsored
Drugs / interventionsbevacizumab, chemotherapy, radiation
Locations19 sites (Little Rock, Arkansas and 18 other locations)
Trial IDNCT06586957 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of NKT3964 in adults with advanced or metastatic solid tumors. The study consists of a Dose Escalation phase to determine the recommended dose for expansion and an Expansion phase to evaluate the drug's effectiveness based on objective response rates. Eligible participants must have pathologically confirmed unresectable tumors that have progressed after standard treatments. The trial focuses on specific cancer types, including ovarian, endometrial, gastric, and triple-negative breast cancers.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced or metastatic solid tumors that have progressed after standard therapies and are refractory or intolerant to existing treatments.

Not a fit: Patients with early-stage solid tumors or those who have not yet undergone standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have limited treatment alternatives.

How similar studies have performed: Other studies involving CDK inhibitors have shown promise in treating similar conditions, suggesting a potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.

Dose Escalation:

1. Ovarian cancer
2. Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
3. Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
4. Small cell lung cancer (SCLC)
5. Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
6. HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy \[ET\])
7. Other solid tumors with CCNE1 amplification

Dose Expansion:

Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate \[ADC\]) in the metastatic setting..

Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification.

Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification as determined by NGS by local liquid or tissue test.

Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification.

Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug.

* Have adequate organ function
* Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception
* Ability to swallow oral medications.
* Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment

Exclusion Criteria:

* Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
* History of another malignancy with exceptions
* History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.
* Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
* Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
* Known active CNS metastases and/or carcinomatous meningitis
* Active interstitial lung disease currently requiring treatment
* History of uveitis, retinopathy or other clinically significant retinal disease
* Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease
* Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964.
* Known human immunodeficiency virus (HIV), active hepatitis B or C infection
* Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
* Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
* Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1

Where this trial is running

Little Rock, Arkansas and 18 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Solid TumorAdvanced Solid TumorSolid Tumor, AdultMetastatic TumorOvarian CancerOvarian NeoplasmsOvarian CarcinomaMetastatic Ovarian Carcinoma
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.