A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

Launched by NIKANG THERAPEUTICS, INC. · Sep 4, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called NKT3964 for adults with advanced or metastatic solid tumors, which are cancers that have spread beyond their original location. The trial aims to find out how safe the treatment is, how well it works against tumors, and to determine the best dose to use in future studies. Specifically, it focuses on patients who have solid tumors like ovarian, endometrial, gastric, and certain types of breast cancers that have not responded to standard treatments.

To be eligible for this trial, participants must have a confirmed diagnosis of an advanced solid tumor that cannot be surgically removed and must have shown disease progression after their last treatment. Key requirements include having adequate organ function and the ability to swallow oral medications. Participants will receive NKT3964 and will be monitored closely for side effects and effectiveness. This trial is currently recruiting participants, and those interested should discuss it with their healthcare provider to see if they qualify and learn more about what participation involves.

Gender

ALL

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 only: subjects must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
• Dose Escalation:
• • 1. Ovarian cancer with CCNE1 amplification
• • 2. Endometrial cancer with 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
• 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 with CCNE1 amplification as determined by NGS by local liquid or tissue test.
• • 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 as determined by NGS by local liquid or tissue test.
• • 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 as determined by NGS by local liquid or tissue test.
• • Part 2E: Advanced/recurrent uterine carcinosarcoma previously treated with 1 prior platinum-based chemotherapy regimen and ≤3 prior lines of systemic therapy, with CCNE1 amplification as determined by NGS by local liquid or tissue test. Prior bevacizumab or PARP inhibitors are allowed and must be at least 3 weeks prior to the start of study drug.
• • 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