OncoMatch/Clinical Trials/NCT06586957
A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
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 CDK2 Degrader NKT3964 in Adults With Advanced/Metastatic Solid Tumors
Is NCT06586957 recruiting? Yes, currently enrolling (Oct 2026). This Phase 1 trial studies multiple treatments including NKT3964 and Paclitaxel for solid tumor.
Treatment: NKT3964 · Paclitaxel · Doxorubicin — The goal of the Monotherapy Dose Escalation phase (Part 1) of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Monotherapy Expansion phase of the study (Part 2) is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D). The goal of the Combination Dose Escalation phase (Part 3) of the study is to identify the RDE of NKT3964 in combination with chemotherapy in adult subjects with advanced/metastatic endometrial cancer. The goal of the Combination Expansion phase of the study (Part 4) is to evaluate the preliminary anti-tumor activity of NKT3964 in combination with chemotherapy at the RDE based on ORR.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Chemotherapy
Other
Cancer type
Tumor Agnostic
Ovarian Cancer
Endometrial Cancer
Triple-Negative Breast Cancer
Breast Carcinoma
Gastric Cancer
Small Cell Lung Cancer
Biomarker criteria
Required: CCNE1 amplification
CCNE1 amplification required for: endometrioid endometrial cancer (Part 1), gastric/GEJ/esophageal adenocarcinoma (Part 1, 2C), other solid tumors (Part 1), advanced platinum-resistant/refractory ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (Part 2B), advanced/metastatic gastric/GEJ/esophageal adenocarcinoma (Part 2C), advanced endometrial adenocarcinoma or uterine papillary serous carcinoma (Part 2D, 3, 4) except clear cell/uterine serous histology
Disease stage
Required: Stage IV, LOCALLY ADVANCED (PART 2A)
advanced and unresectable or metastatic solid tumor; locally advanced and unresectable (Stage III) or metastatic (Stage IV) [Part 2A]
Demographics
Prior therapy
Must have received: systemic therapy — advanced/metastatic disease
documented disease progression on last standard treatment
Must have received: CDK4/6 inhibitor — HR+ and HER2- breast cancer
must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy [ET]
Must have received: systemic therapy — Part 2A: HR+ and HER2- breast cancer, metastatic or locally advanced
previously treated with ≥1 line of standard of care (SOC) including CDK4/6 inhibitor plus ET and not suitable for further ET. Subjects must have progressed after receiving therapy for ≥3 months in the metastatic setting or for ≥6 months in the adjuvant setting. Subjects must have received ≤2 lines of systemic cytotoxic therapy (chemotherapy or cytotoxic antibody drug conjugate [ADC]) in the metastatic setting.
Must have received: platinum-based chemotherapy — Part 2B: advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer
progression on at least one platinum containing therapy and previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease and with CCNE1 amplification
Must have received: systemic therapy — Part 2C: advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma
progression on at least one systemic therapy and previously treated with ≤3 prior lines of systemic therapy administered for advanced/metastatic disease, with CCNE1 amplification
Must have received: systemic therapy — Part 2D: advanced endometrial adenocarcinoma or uterine papillary serous carcinoma
previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease with CCNE1 amplification
Must have received: platinum-based chemotherapy — Part 2E: advanced/recurrent uterine carcinosarcoma
previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy
Cannot have received: CDK2 inhibitor
Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
Cannot have received: paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil (paclitaxel)
Prior severe hypersensitivity reaction to paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil (Cohort 3A and 4A only)
Cannot have received: doxorubicin or other anthracyclines or anthracenediones (doxorubicin)
severe hypersensitivity reaction to doxorubicin or any other component of the product, other anthracyclines or anthracenediones (Cohort 3B and 4B)
Lab requirements
Liver function
Have adequate organ function; Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder [excluded]
Cardiac function
Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment; Left ventricular ejection fraction (LVEF) <50% (Cohort 3B/4B); Active cardiac conditions including myocarditis, pericarditis, or clinically significant valvular heart disease; Known elevated cardiac biomarkers at baseline; History of anthracycline-related cardiomyopathy regardless of recovery; Cumulative lifetime exposure to doxorubicin exceeding 450 mg/m2 (Cohort 3B/4B)
Have adequate organ function; Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder [excluded]; Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment; LVEF <50% (Cohort 3B/4B); Active cardiac conditions including myocarditis, pericarditis, or clinically significant valvular heart disease; Known elevated cardiac biomarkers at baseline; History of anthracycline-related cardiomyopathy regardless of recovery; Cumulative lifetime exposure to doxorubicin exceeding 450 mg/m2 (Cohort 3B/4B)
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- University of Arkansas Medical School · Little Rock, Arkansas
- University of California - Los Angeles · Los Angeles, California
- UCSF · San Francisco, California
- SCRI at HealthOne · Denver, Colorado
- Florida Cancer Specialists & Research Institute · Lake Mary, Florida
Showing up to 5 US sites.
See all sites on ClinicalTrials.gov →Frequently asked questions
Is NCT06586957 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior CDK2 inhibitor, paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil, doxorubicin or other anthracyclines or anthracenediones disqualifies patients from enrollment.
Does this trial require CCNE1?
Yes, CCNE1 amplification is a required biomarker for enrollment.
What disease stage is eligible?
Stage IV or LOCALLY ADVANCED (PART 2A) is required.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages