A Study With NKT3447 for Adults With Advanced/Metastatic Solid Tumors

NCT06264921 | Terminated Phase 1 FDA Drug

• 1 other identifier: NKT3447-101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 8

Brief Summary

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) to determine the maximum tolerated dose (MTD) and/or preliminary recommended dose for expansion (RDE) of NKT3447 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), and the preliminary antitumor activity of NKT3447 in adult subjects with cyclin E1 (CCNE1) amplified ovarian cancer at the RDEs selected in Dose Escalation and to determine the preliminary recommended phase 2 dose (RP2D).

Conditions

Solid Tumor; Solid Tumor, Adult; Advanced Solid Tumor; Metastatic Tumor; Ovarian Cancer; Ovarian Neoplasms; Ovarian Carcinoma; Metastatic Ovarian Carcinoma; Endometrial Cancer; Endometrial Neoplasms; Endometrial Diseases; Metastatic Endometrial 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 Cancer; 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

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 years

• Duration of Response (DOR)

  2 years

• Disease control rate

  1 year

• Overall Survival (OS)

  2 years

• 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 NKT3447 at increasing dosage levels to determine the MTD and/or preliminary RDEs.

Drug: NKT3447

Dose Expansion

EXPERIMENTAL

Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D.

Drug: NKT3447

Interventions

NKT3447 DRUG

Oral CDK2 inhibitor

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 confirmed unresectable advanced/metastatic solid tumors (as outlined below) with disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment likely to improve the disease outcome in the judgment of the Investigator.
• Measurable disease per the RECIST v1.1
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Able to swallow oral medications.
• Dose Escalation(Part 1):
• Ovarian cancer
• Endometrial cancer
• Gastric cancer or gastroesophageal junction cancer
• Small cell lung cancer (SCLC)
• Triple-negative breast cancer (human epidermal growth factor receptor 2 \[HER2\], estrogen receptor \[ER\], progesterone receptor negative)
• ER/progesterone-receptor positive, HER2 negative breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and not suitable for endocrine therapy)
• Other solid tumors with CCNE1 amplification as determined by NGS by local liquid or tissue biopsy.
• Dose Expansion (Part 2):
• a. Platinum resistant or refractory ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least 1 platinum containing therapy with CCNE1 amplification as determined by NGS by local liquid or tissue biopsy.
• Measurable disease per the RECIST v1.1

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
• Visceral crisis with life-threatening complications, lymphangitic spread, CNS metastasis and/or carcinomatous meningitis
• Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
• Clinically active interstitial lung disease
• History of uveitis, retinopathy or other clinically significant retinal disease
• Has known human immunodeficiency virus (HIV), active hepatitis B or C infection
• Prior CDK2 inhibitor
• Major surgery within 2 months or minor surgery within 10 days before the first dose of NKT3447

Sponsors & Collaborators

• NiKang Therapeutics, Inc.: lead

Study Sites (8)

University of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

AdventHealth Cancer Institute

Celebration, Florida, 34747, United States

Location

Augusta University Georgia Cancer Center

Augusta, Georgia, 30909, United States

Location

Norton Cancer Institute - Broadway

Louisville, Kentucky, 40202, United States

Location

The Gabrail Pharmacology Phase 1 Research Center

Canton, Ohio, 44718, United States

Location

Texas Oncology-Austin Midtown NEXT Oncology

Austin, Texas, 78758, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

MeSH Terms

Conditions

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

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; 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; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

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

Model Details: Dose Escalation and Dose Expansion

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 20, 2024
• Study Start: February 23, 2024
• Primary Completion: April 7, 2025
• Study Completion: April 16, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)