HR+ Breast CancerPhase 1NCT07029399
A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors
A Phase 1 study testing NKT5097 CDK2/CDK4 dual degrader, Fulvestrant and Letrozole in people with HR+ Breast Cancer and Triple Negative Breast Cancer (TNBC), run by NiKang Therapeutics, Inc. at 18 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors
- What is being tested?
- NKT5097 CDK2/CDK4 dual degrader, Fulvestrant and Letrozole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 361 participants
- Where
- 18 sitesUnited States
- Study dates
- 25 Mar 2025to 31 Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
United States18 sites, 18 recruiting
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Dana Faber Institutional clinical.gov contact, 877-338-7425
Antonio Giordano, MD
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Cancer Answer, 216-444-7923, TaussigResearch@ccf.org
Azka Ali, MD
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Jennifer Knight, 214-645-7097, Jennifer.Knight@UTSouthwestern.edu
Nisha Unni, MD
- Recruiting
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
SCRI Contact Email, 720-754-2610, CANN.DDUDenverGeneral@SarahCannon.com
Gerald Falchook, MD
- Recruiting
City of Hope
Duarte, California, 91010
Jenny Sanchez, 949-671-4920, jesanchez@coh.org
Hope Rugo, MD
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Blake Patterson, 703-783-4505, bpatterson@nextoncology.com
Alexander Spira
- Recruiting
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546
Ashley Spagnuolo, 616.954.5552, ashley.spagnuolo@startresearch.com
Manish Sharma
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ileana Gutierrez, 832-829-2161, ilgutierrez@mdanderson.org
Timothy Yap, MD
- Recruiting
University of Iowa
Iowa City, Iowa, 52242
Clinical Trial Inquiry Line, 319-353-8155, kerri-fitch@uiowa.edu
Mark Burkard, MD
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92037
Cristal Martinez, 858-822-5223, cmm015@health.ucsd.edu
Rebecca Shatsky, MD
- Recruiting
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Ann Lovelace, 702-609-9460, Ann.lovelace@usoncology.com
Fadi Braiteh, MD
- Recruiting
West Virginia University
Morgantown, West Virginia, 26506
Emily Hawkins, 304-293-7375, emily.hawkins@hsc.wvu.edu
Bei Jiang, MD, PhD
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06520
Priscilla Steve, 203-785-4069, Priscilla.Steve@yale.edu
Adriana Kahn, MD
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Julie Urban, 412-623-7396, IDDCReferrals@upmc.edu
Marija Balic, MD, PhD, MBA
- Recruiting
South Texas Accelerated Research Therapeutics (START) San Antonio
San Antonio, Texas, 78229
Isabel Jimenez, 210-593-5265, isabel.jimenez@startresearch.com
Amita Patnaik
- Recruiting
SCRI Florida Cancer Specialists - Sarasota
Sarasota, Florida, 34232
Carly Taylor, 941-377-9993, ctaylor@flcancer.com
Judy Wang, MD
- Recruiting
Washington University
St Louis, Missouri, 63110
Katlyn Kraft, 314-747-5440, Katlyn.Kraft@wustl.edu
Faisal Fa'ak, MD
- Recruiting
South Texas Accelerated Research Therapeutics (START) Mountain Region
West Valley City, Utah, 84119
HOPE Team, 801-907-4750, hopeteam@startresearch.com
William McKean
About this study
Official title: 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
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
Read the detailed description
This First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of NKT5097, a novel dual protein degrader of CDK2 and CDK4, is split into 3 Parts:
Part 1: Monotherapy Dose Escalation in selected advanced/metastatic non-CNS primary solid tumors will be enrolled based on a projected total of 5 dose levels
Part 2: Food Effect Analysis: Subjects with solid tumors (as noted in Part 1) will be enrolled (by backfilling selected dose cohorts) to evaluate the effect of dosing with food on NKT5097.
Part 3: Monotherapy Tumor-specific Expansion: Subjects may be enrolled (by backfilling selected dose cohorts) into each selected tumor-specific cohort. One or more of these cohorts may be opened at the discretion of the Sponsor in consultation with the DEC
Part 4: Combination Dose Escalation with ET in selected HR+/HER2- breast cancer will be enrolled based on a projected 2 dose levels
Part 5: Combination Dose Expansion with ET in HR+/HER2- breast cancer in one or more various cohorts
In addition to the above, the study will explore pharmacokinetics, various pharmacodynamic biomarkers, gene mutations, and tumor responses such as PFS and DOR.
- Conditions
- HR+ Breast Cancer, Triple Negative Breast Cancer (TNBC), CCNE1 Amplified Advanced Solid Tumors, HR+ HER2- Breast Cancer
- Being tested
- NKT5097 CDK2/CDK4 dual degrader, Fulvestrant, Letrozole
- Keywords
- CCNE1, cyclin E1, triple negative breast cancer, TNBC, estrogen receptor positive, HER2-, breast cancer, post CDK4/6i, HER2 expression, Fulvestrant, Letrozole, endocrine therapy, refractory, endocrine resistant, endocrine sensitivity, metastatic
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKT5097 CDK2/CDK4 dual degraderDrug
NKT5097 will be distributed in tablet form and dosed daily or twice a day
FulvestrantDrug
Fulvestrant will be administered as an injection and dosed on C1D1, C1D15 and Day 1 of every cycle thereafter.
LetrozoleDrug
Letrozole will be administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Escalation of orally administered NKT5097 Receives: Drug: NKT5097 CDK2/CDK4 dual degrader |
| Part 2 Food Effect | Experimental | Orally administered NKT5097 with and without meal Receives: Drug: NKT5097 CDK2/CDK4 dual degrader |
| Part 3 Expansion | Experimental | Expansion of dose levels based upon safety and PK following Part 1 escalation. Receives: Drug: NKT5097 CDK2/CDK4 dual degrader |
| Part 4 Combination Dose Escalation | Experimental | Escalation of orally administered NKT5097 in combination with Endocrine Therapy (ET) Receives: Drug: NKT5097 CDK2/CDK4 dual degrader; Drug: Fulvestrant; Drug: Letrozole |
| Part 5 Combination Expansion | Experimental | Expansion of dose levels based upon safety and PK following Part 4 escalation Receives: Drug: NKT5097 CDK2/CDK4 dual degrader; Drug: Fulvestrant; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities as Assessed by CTCAE
Measured: 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
Measured: From enrollment through end of treatment up to 2 years
Maximum concentration Cmax after a single dose and multiple doses
Measured: 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)
Measured: Day 1 and Day 15 of Cycle 1 ((Cycle 1 is 28 days)
Maximum concentration (Cmax) when dosed with and without food
Measured: 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)
Measured: Day 1 through Day 3 of Cycle 1 (Cycle 1 is 28 days)
Time to maximum plasma concentration (Tmax) after a single dose and multiple doses
Measured: Day 1 through Day 3 and Day 15 of Cycle 1 (Cycle 1 is 28 days)
Investigator-assessed ORR by RECIST v1.1
Measured: From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Investigator-assessed PFS by RECIST v1.1
Measured: From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Duration of Response (DOR)
Measured: From enrollment (Day 1) through end of treatment (up to 3 years) with an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2025
- Study start25 Mar 2025
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HR+ Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 361 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NiKang Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07029399
- Sponsor's protocol ID
- NKT5097-101
- Status last verified
- Aug 2026
- First submitted
- 28 May 2025
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No