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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

Phase
Phase 1
Sponsor
NiKang Therapeutics, Inc.
Enrollment
150
Timeline
Sep 2024 → May 2029
About This Study

The goal of the Dose Escalation phase 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 Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDEs based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).

Eligibility Criteria

Inclusion Criteria

  • 1\- Must have a pathologically confirmed advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. Part 1 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
  • 2Dose Escalation:
  • 3Ovarian cancer
  • 4Endometrial cancer (only endometrioid subtype will require CCNE1 amplification)
  • 5Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
  • 6Small cell lung cancer (SCLC)
  • 7Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
  • 8HR+ (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 \[ET\])
  • 9Other solid tumors with CCNE1 amplification
  • 10Dose Expansion:
  • 11Part 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..
  • 12Part 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.
  • 13Part 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 as determined by NGS by local liquid or tissue test.
  • 14Part 2D: Advanced endometrial adenocarcinoma or uterine papillary serous carcinoma previously treated with ≤4 prior lines of systemic therapy administered for advanced/metastatic disease (only 'endometrioid' subtype will require CCNE1 amplification as determined by NGS by local liquid or tissue test).
  • 15Part 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.
  • 16Have adequate organ function
  • 17Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception
  • 18Ability to swallow oral medications.
  • 19Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment

Exclusion Criteria

  • 1Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or radiotherapy, or chemotherapy.
  • 2History of another malignancy with exceptions
  • 3History of lymphohistiocytic or lymphoid hyperplasia; hemophagocytic lymphohistiocytosis.
  • 4Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
  • 5Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
  • 6Known active CNS metastases and/or carcinomatous meningitis
  • 7Active interstitial lung disease currently requiring treatment
  • 8History of uveitis, retinopathy or other clinically significant retinal disease
  • 9Active or chronic corneal disorders, other active ocular conditions requiring ongoing therapy, or any clinically significant corneal disease
  • 10Active wound healing from major surgery within 1 month or minor surgery within 10 days before the first dose of NKT3964.
  • 11Known human immunodeficiency virus (HIV), active hepatitis B or C infection
  • 12Prior investigative treatment with a selective or nonselective CDK2 inhibitor or degrader
  • 13Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
  • 14Palliative radiation therapy within 14 days or other radiation therapy within 4 weeks prior to C1D1

Locations

19 sites participating in this study

Emory Winship Cancer Institute

Atlanta, Georgia 30322

Recruiting

Jennifer Scalici, MD

University of Arkansas Medical School

Little Rock, Arkansas 72205

Recruiting

Michael Birrer, MD

University of California - Los Angeles

Los Angeles, California 90095

Recruiting

Gottfried Konecny, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →