RecruitingPhase 1

A Study With NKT3964 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 CDK2 Degrader NKT3964 in Adults With Advanced/Metastatic Solid Tumors

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
19 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests NKT3964 alone in adults with certain solid tumors that are advanced or have spread. It also tests NKT3964 with chemotherapy for advanced cancer of the lining of the uterus. Researchers want to find suitable doses, check safety, and see how well treatment fights cancer.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have a cancer confirmed by a tissue test that cannot be removed by surgery or has spread, and that grew during your last standard treatment.
  • For Part 1, have an eligible ovarian, uterine lining, stomach, esophagus, lung, breast, or other solid tumor. Some cancers must have extra copies of the CCNE1 gene. Treatments known to help must have stopped working or caused side effects you could not tolerate.
  • For Part 2, have an eligible breast, ovarian, fallopian tube, abdominal lining, stomach, esophagus, or uterine cancer. Each group has specific rules about cancer type, CCNE1 gene changes, and past treatments.
  • For Parts 3 and 4, have an eligible uterine lining cancer and no more than 4 past drug treatment courses for advanced cancer. Extra CCNE1 gene copies are usually required, with exceptions for certain cancer types.
  • Your organs must work well enough for the study.
  • If you have female reproductive organs, you must have had surgery that prevents pregnancy, be past menopause, or agree to use highly effective birth control.
  • Be able to swallow medicine.
  • Agree to provide stored tumor tissue and paired tumor samples taken before treatment.

Who can't join

  • Your cancer could be treated with the goal of a cure. A history of another cancer may also exclude you, with some exceptions.
  • Have certain conditions involving excess immune cells or severe immune system overactivity; known HIV; active hepatitis B or C; or serious liver disease.
  • Have not recovered from past cancer treatment to your usual health or only mild side effects; are still healing from recent surgery; or had radiation too recently.
  • Have active cancer spread to the brain, spinal cord, or their lining, or active lung tissue disease that needs treatment.
  • Have certain eye conditions, including inflammation inside the eye, damage to the retina at the back of the eye, or disease of the clear front surface.
  • Had a major heart or blood vessel event in the past 6 months. Groups 3B and 4B also exclude certain heart problems, abnormal heart tests, or too much lifetime doxorubicin exposure.
  • Previously received an experimental drug that blocks or breaks down CDK2, a protein involved in cell growth.
  • For combination groups, have had a severe allergic reaction to the assigned chemotherapy or related drugs or ingredients: paclitaxel for groups 3A and 4A, or doxorubicin for groups 3B and 4B.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: \- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 Monotherapy Dose Escalation (including Food Effect Sub-study): subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. Part 1 Monotherapy Dose Escalation: 1. Ovarian cancer 2. Endometrial cancer (only endometrioid subtype will require CCNE1 amplification) 3. Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification 4. Small cell lung cancer (SCLC) 5. Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative) 6. HR+ (includes estrogen-receptor or progesterone-receptor) and HER2- breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and is not suitable for endocrine therapy \[ET\]) 7. Other solid tumors with CCNE1 amplification * \- Part 2 Monotherapy Dose Expansion: * Part 2A: HR+ and HER2- breast cancer that is locally advanced and unresectable (Stage III) or metastatic (Stage IV); 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.. * Part 2B: Advanced platinum-based-chemotherapy resistant or refractory epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with 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. * Part 2C: Advanced unresectable or metastatic gastric, GEJ or esophageal adenocarcinoma with 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. * 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. Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor. * Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug. * -Part 3 Combination Dose Escalation: * 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. (Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor) * -Part 4 Combination Dose Expansion: * 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. (Subjects with clear cell carcinoma or uterine serous carcinoma histology may be considered regardless of CCNE1 status after discussion and approval from the Sponsor) * Have adequate organ function * Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception * Ability to swallow oral medications. * Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment Exclusion Criteria: * Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy. * History of another malignancy with exceptions * History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis. * Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE) * Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment * Known active CNS metastases and/or carcinomatous meningitis * Active interstitial lung disease currently requiring treatment * History of uveitis, retinopathy or other clinically significant retinal disease * Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease * Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964. * Known human immunodeficiency virus (HIV), active hepatitis B or C infection * Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader * Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder * Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1 * Prior severe hypersensitivity reaction to paclitaxel or other drugs formulated in Polyoxyl 35 Castor Oil (Cohort 3A and 4A only) or severe hypersensitivity reaction to doxorubicin or any other component of the product, other anthracyclines or anthracenediones (Cohort 3B and 4B). * \- For subjects in Cohort 3B or 4B only: * Left ventricular ejection fraction (LVEF) \<50% as measured by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 4 weeks prior to first dose * 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, including planned doxorubicin in Part 3b or Part 4b, exceeding 450 mg/m2

Study sites (19)

AR

CA

CO

FL

GA

KS

MA

NJ

PA

TN

TX

UT

VA