NKT5097 CDK2/CDK4 dual degrader: NKT5097 will be distributed in tablet form and dosed daily or twice a day
Fulvestrant: Fulvestrant will be administered as an injection and dosed on C1D1, C1D15 and Day 1 of every cycle thereafter.
Letrozole: Letrozole will be administered orally once daily.
Study 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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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)
Primary outcome measure(s)
Incidence of dose-limiting toxicities as Assessed by CTCAE — From enrollment through end of safety monitoring period of 28 days from first dose
Trial sites (18)
Facility
City
Region
Status
City of Hope
Duarte
California
Recruiting
UC San Diego Moores Cancer Center
La Jolla
California
Recruiting
Sarah Cannon Research Institute at HealthONE
Denver
Colorado
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
SCRI Florida Cancer Specialists - Sarasota
Sarasota
Florida
Recruiting
University of Iowa
Iowa City
Iowa
Recruiting
Dana-Farber Cancer Institute
Boston
Massachusetts
Recruiting
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids
Michigan
Recruiting
Washington University
St Louis
Missouri
Recruiting
Comprehensive Cancer Centers of Nevada
Las Vegas
Nevada
Recruiting
Cleveland Clinic
Cleveland
Ohio
Recruiting
UPMC Hillman Cancer Center
Pittsburgh
Pennsylvania
Recruiting
University of Texas Southwestern Medical Center
Dallas
Texas
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
South Texas Accelerated Research Therapeutics (START) San Antonio
San Antonio
Texas
Recruiting
South Texas Accelerated Research Therapeutics (START) Mountain Region
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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