A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

April 16, 2026 updated by: NiKang Therapeutics, Inc.

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

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Inclusion Criteria:

- Must have a pathologically confirmed, advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment.

For Part 1 only: Patients must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.

Part 1 Dose Escalation and Food Effect Sub-study:

  1. Ovarian cancer
  2. Endometrial cancer (only 'endometrioid' subtype requires 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

Part 2 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 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) 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.

  • Measurable disease per RECIST v1.1, except for subjects with HR+/HER2- breast cancer or endometrial cancer (Part 1) who must have measurable or evaluable (including skin or bone lesion only) disease.
  • Age ≥18 years
  • ECOG PS 0-1
  • Have adequate organ function
  • Subjects with female reproductive organs must be surgically sterile, post-menopausal, or, if of child-bearing potential, must meet pre-specified criteria
  • Subjects who are capable of insemination must meet pre-specified criteria
  • Ability to swallow oral medications.
  • Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment and on-treatment.

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
  • Clinically 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

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas Medical School
        • Principal Investigator:
          • Michael Birrer, MD
        • Contact:
    • California
      • Los Angeles, California, United States, 90095
        • Not yet recruiting
        • University of California - Los Angeles
        • Principal Investigator:
          • Gottfried Konecny, MD
      • San Francisco, California, United States, 94158
        • Withdrawn
        • UCSF
    • Colorado
      • Denver, Colorado, United States, 80218
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Terminated
        • Florida Cancer Specialists & Research Institute
      • Orlando, Florida, United States, 32804
        • Recruiting
        • AdventHealth Cancer Institute
        • Principal Investigator:
          • Guru Sonpavde, MD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory Winship Cancer Institute
        • Principal Investigator:
          • Jennifer Scalici, MD
        • Contact:
      • Augusta, Georgia, United States, 30912
        • Not yet recruiting
        • Augusta University
        • Principal Investigator:
          • Sharad Ghamande, MD
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Withdrawn
        • University of Kansas
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
        • Principal Investigator:
          • Elizabeth LEE, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center At Hackensack UMC
        • Principal Investigator:
          • Martin Gutierrez, MD
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Sidney Kimmell Cancer Center - Jefferson Health
        • Contact:
          • Sarah Cannon Research Institute
          • Phone Number: 844-482-4812
        • Principal Investigator:
          • Ida Micaily, MD
      • Pittsburgh, Pennsylvania, United States, 15213
        • Withdrawn
        • UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute (SCRI)
        • Principal Investigator:
          • Denise Yardley, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78758
        • Recruiting
        • NEXT Oncology
        • Contact:
        • Principal Investigator:
          • Sheena Sahota, MD
      • Dallas, Texas, United States, 75235
    • Utah
      • Salt Lake City, Utah, United States, 84145
        • Recruiting
        • Intermountain Health
        • Contact:
        • Principal Investigator:
          • Caroline Nebhan, MD
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Linda Duska, MD
        • Contact:
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Virginia
        • Principal Investigator:
          • Alexander Spira, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3964 at increasing dosage levels to determine the MTD and/or preliminary RDEs.
Drug: NKT3964
Oral CDK2 Degrader
Experimental: Dose Expansion
Dose expansion will include the RDE selected to determine the preliminary antitumor activity and the RP2D.
Drug: NKT3964
Oral CDK2 Degrader

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Dose Limiting Toxicity (DLT) events
Time Frame: 28 Days
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
28 Days
Objective Response Rate (ORR)
Time Frame: 1 Year
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by the Investigator
1 Year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 2 Year
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.
2 Year
Overall Survival (OS)
Time Frame: 2 Year
OS defined as the time from the date the participant started study drug to death for any reason.
2 Year
Time to Response (TTR)
Time Frame: 1 Year
TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.
1 Year
Number of Participants with Adverse Events
Time Frame: 2 Year
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 Year
Observed trough concentration of NKT3964 (Ctrough)
Time Frame: 88 Weeks
Observed trough concentration of NKT3964 (Ctrough)
88 Weeks
Duration of Response (DOR)
Time Frame: 2 Year
Duration of overall response is defined as the time from the date of first confirmed CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) including clinical progression, or death due to any cause, or the start of subsequent anticancer therapy, whichever occurred first.
2 Year
Disease control rate
Time Frame: 1 Year
Disease control rate defined as CR + PR + stable disease [SD] for at least 8 weeks
1 Year
Maximum observed plasma concentration (Cmax) of NKT3964 with and without a high-fat and/or low-fat meal
Time Frame: 1 Month
Maximum observed plasma concentration (Cmax) of NKT3964
1 Month
Time to maximum observed plasma concentration of NKT3964 (Tmax) with and without a high-fat and/or low-fat meal
Time Frame: 1 Month
Time to maximum observed plasma concentration of NKT3964 (Tmax)
1 Month
Area under the plasma concentration-time curve (AUC0-t) of NKT3964 with and without a high-fat and/or low-fat meal
Time Frame: 1 Month
Area under the plasma concentration-time curve (AUC0-t) of NKT3964
1 Month
Apparent clearance (CL/F) of NKT3964
Time Frame: 1 Month
Apparent clearance (CL/F)
1 Month
Apparent volume of distribution (V/F) of NKT3964
Time Frame: 1 Month
Apparent volume of distribution (V/F)
1 Month
Half-life (t1/2) of NKT3964
Time Frame: 1 Month
Half-life (t1/2)
1 Month
Accumulation ratio (AR) of NKT3964
Time Frame: 1 Month
Accumulation ratio (AR)
1 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NiKang Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2024

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

September 4, 2024

First Submitted That Met QC Criteria

September 4, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 16, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKT3964-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD are not planned to be shared at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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