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

NCT06586957 | Recruiting Phase 1 FDA Drug

• 1 other identifier: NKT3964-101
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 19

Brief Summary

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).

Conditions

Solid Tumor; Advanced Solid Tumor; Solid Tumor, Adult; Metastatic Tumor; Ovarian Cancer; Ovarian Neoplasms; Ovarian Carcinoma; Metastatic Ovarian Carcinoma; Endometrial Neoplasms; Endometrial Diseases; Metastatic Endometrial Cancer; Triple Negative Breast Cancer; Metastatic Endometrial Carcinoma; Advanced Endometrial Carcinoma; Advanced Ovarian Carcinoma; Gastric Cancer; Advanced Gastric Carcinoma; Metastatic Gastric Cancer; Metastatic Gastric Carcinoma; Small Cell Lung Cancer; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms; Platinum-resistant Ovarian Cancer; Platinum-refractory Ovarian Carcinoma; CCNE1 Amplification; Hormone Receptor Negative Breast Carcinoma; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Progesterone-receptor-positive Breast Cancer

Keywords

CDK 2 Inhibitor; CDK 4 Inhibitor; CDK 6 Inhibitor; CDK2 Degrader; Protein Degrader; PROTAC

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Dose Limiting Toxicity (DLT) events

  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)

  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 Outcomes (14)

• Progression-free survival (PFS)

  2 Year

• Duration of Response (DOR)

  2 Year

• Disease control rate

  1 Year

• Overall Survival (OS)

  2 Year

• Time to Response (TTR)

  1 Year

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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

Dose Expansion

EXPERIMENTAL

Dose expansion will include the RDE selected to determine the preliminary antitumor activity and the RP2D.

Drug: NKT3964

Interventions

NKT3964 DRUG

Oral CDK2 Degrader

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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:
• Ovarian cancer
• Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
• Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
• Small cell lung cancer (SCLC)
• Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
• 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 \[ET\])
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NiKang Therapeutics, Inc.: lead

Study Sites (19)

University of Arkansas Medical School

Little Rock, Arkansas, 72205, United States

RECRUITING

University of California - Los Angeles

Los Angeles, California, 90095, United States

NOT YET RECRUITING

UCSF

San Francisco, California, 94158, United States

WITHDRAWN

SCRI at HealthOne

Denver, Colorado, 80218, United States

RECRUITING

Florida Cancer Specialists & Research Institute

Lake Mary, Florida, 32746, United States

TERMINATED

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

RECRUITING

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Augusta University

Augusta, Georgia, 30912, United States

NOT YET RECRUITING

University of Kansas

Fairway, Kansas, 66205, United States

WITHDRAWN

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

John Theurer Cancer Center at Hackensack UMC

Hackensack, New Jersey, 07601, United States

RECRUITING

Sidney Kimmell Cancer Center - Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

UPMC

Pittsburgh, Pennsylvania, 15213, United States

WITHDRAWN

Sarah Cannon Research Institute (SCRI)

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Oncology

Austin, Texas, 78758, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75235, United States

RECRUITING

Intermountain Health

Salt Lake City, Utah, 84145, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Ovarian Neoplasms; Endometrial Neoplasms; Uterine Diseases; Triple Negative Breast Neoplasms; Stomach Neoplasms; Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Sponsor Contact

CONTACT

(302) 596-8654; clinicaltrials@nikangtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation and Dose Expansion

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: September 19, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)