A Study With NKT5097 for Adults With Advanced/Metastatic Solid Tumors

Purpose

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

Conditions

  • HR+ Breast Cancer
  • Triple Negative Breast Cancer (TNBC)
  • CCNE1 Amplified Advanced Solid Tumors
  • HR+ HER2- Breast Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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)

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 Dose Escalation 		Escalation of orally administered NKT5097
  • Drug: NKT5097 CDK2/CDK4 dual degrader
    NKT5097 will be distributed in tablet form and dosed daily or twice a day
Experimental
Part 2 Food Effect 		Orally administered NKT5097 with and without meal
  • Drug: NKT5097 CDK2/CDK4 dual degrader
    NKT5097 will be distributed in tablet form and dosed daily or twice a day
Experimental
Part 3 Expansion 		Expansion of dose levels based upon safety and PK following Part 1 escalation.
  • Drug: NKT5097 CDK2/CDK4 dual degrader
    NKT5097 will be distributed in tablet form and dosed daily or twice a day
Experimental
Part 4 Combination Dose Escalation 		Escalation of orally administered NKT5097 in combination with Endocrine Therapy (ET)
  • Drug: NKT5097 CDK2/CDK4 dual degrader
    NKT5097 will be distributed in tablet form and dosed daily or twice a day
  • Drug: Fulvestrant
    Fulvestrant will be administered as an injection and dosed on C1D1, C1D15 and Day 1 of every cycle thereafter.
  • Drug: Letrozole
    Letrozole will be administered orally once daily.
Experimental
Part 5 Combination Expansion 		Expansion of dose levels based upon safety and PK following Part 4 escalation
  • Drug: NKT5097 CDK2/CDK4 dual degrader
    NKT5097 will be distributed in tablet form and dosed daily or twice a day
  • Drug: Fulvestrant
    Fulvestrant will be administered as an injection and dosed on C1D1, C1D15 and Day 1 of every cycle thereafter.
  • Drug: Letrozole
    Letrozole will be administered orally once daily.

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University
St Louis, Missouri 63110
Contact:
Katlyn Kraft
314-747-5440
Katlyn.Kraft@wustl.edu

More Details

NCT ID
NCT07029399
Status
Recruiting
Sponsor
NiKang Therapeutics, Inc.

Study Contact

Sponsor Contact
302-596-8654
clinicaltrials@nikangtx.com

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.