A Study With NKT5097 for Adults With Advanced/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
1 other identifier
interventional
361
1 country
18
Brief Summary
The goal of this open-label dose escalation and expansion study is to evaluate the safety and tolerability of NKT5097 in adults with advanced/metastatic tumors (emphasis on breast cancer and solid tumors with CCNE1 amplification). Main questions to answer include:
- What is the recommended dose for expansion and/or Phase 2, for both monotherapy and in combination with ET
- What medical issues/symptoms do participants experience when taking NKT5097 as monotherapy as well as in combination with ET
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2025
Typical duration for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 25, 2025
CompletedFirst Submitted
Initial submission to the registry
May 28, 2025
CompletedFirst Posted
Study publicly available on registry
June 19, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
June 26, 2026
June 1, 2026
2.4 years
May 28, 2025
June 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of dose-limiting toxicities as Assessed by CTCAE
From enrollment through end of safety monitoring period of 28 days from first dose
Secondary Outcomes (9)
Incidence of adverse events (AEs) as defined by CTCAE Version 5
From enrollment through end of treatment up to 2 years
Maximum concentration Cmax after a single dose and multiple doses
Day 1 and Day 15 of Cycle 1 (Cycle 1 is 28 days)
Area under the concentration-time curve (AUC last) after a single dose and multiple doses from first dose through the last timepoint with quantifiable concentration (Tlast)
Day 1 and Day 15 of Cycle 1 ((Cycle 1 is 28 days)
Maximum concentration (Cmax) when dosed with and without food
Day 1 and Day 2 of Cycle 1 (Cycle 1 is 28 days)
Area under the concentration-time curve (AUC last) when dosed with and without food from dosing through the last timepoint with quantifiable concentration (Tlast)
Day 1 through Day 3 of Cycle 1 (Cycle 1 is 28 days)
- +4 more secondary outcomes
Study Arms (5)
Part 1 Dose Escalation
EXPERIMENTALEscalation of orally administered NKT5097
Part 2 Food Effect
EXPERIMENTALOrally administered NKT5097 with and without meal
Part 3 Expansion
EXPERIMENTALExpansion of dose levels based upon safety and PK following Part 1 escalation.
Part 4 Combination Dose Escalation
EXPERIMENTALEscalation of orally administered NKT5097 in combination with Endocrine Therapy (ET)
Part 5 Combination Expansion
EXPERIMENTALExpansion of dose levels based upon safety and PK following Part 4 escalation
Interventions
NKT5097 will be distributed in tablet form and dosed daily or twice a day
Fulvestrant will be administered as an injection and dosed on C1D1, C1D15 and Day 1 of every cycle thereafter.
Letrozole will be administered orally once daily.
Eligibility Criteria
You may qualify if:
- Able to provide written informed consent
- Advanced unresectable or metastatic solid tumor (Part 1, 2 \& 3 only)
- Advanced unresectable or metastatic HR+/HER2- breast cancer (Part 4 \& 5 only)
- Refractory to or unable to tolerate existing therapies (Part 1, 2 \& 4 only)
- Measurable or evaluable disease (Part 1, 2, \& 4 only).
- Measurable disease (Part 3 \& 5 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
You may not qualify if:
- 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)
- Should not have received any prior selective investigational inhibitors or degraders (Part 5 only)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
City of Hope
Duarte, California, 91010, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92037, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218, United States
Yale Cancer Center
New Haven, Connecticut, 06520, United States
SCRI Florida Cancer Specialists - Sarasota
Sarasota, Florida, 34232, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546, United States
Washington University
St Louis, Missouri, 63110, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
South Texas Accelerated Research Therapeutics (START) San Antonio
San Antonio, Texas, 78229, United States
South Texas Accelerated Research Therapeutics (START) Mountain Region
West Valley City, Utah, 84119, United States
NEXT Virginia
Fairfax, Virginia, 22031, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 28, 2025
First Posted
June 19, 2025
Study Start
March 25, 2025
Primary Completion (Estimated)
July 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
June 26, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share