A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
Purpose
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).
Conditions
- Solid Tumor
- Advanced Solid Tumor
- Solid Tumor, Adult
- Metastatic Tumor
- Ovarian Cancer
- Ovarian Neoplasms
- Ovarian Carcinoma
- Metastatic Ovarian Carcinoma
- Endometrial Neoplasms
- Endometrial Diseases
- Metastatic Endometrial Cancer
- Triple Negative Breast Cancer
- Metastatic Endometrial Carcinoma
- Advanced Endometrial Carcinoma
- Advanced Ovarian Carcinoma
- Gastric Cancer
- Advanced Gastric Carcinoma
- Metastatic Gastric Cancer
- Metastatic Gastric Carcinoma
- Small Cell Lung Cancer
- Small Cell Lung Carcinoma
- Triple Negative Breast Neoplasms
- Platinum-resistant Ovarian Cancer
- Platinum-refractory Ovarian Carcinoma
- CCNE1 Amplification
- Hormone Receptor Negative Breast Carcinoma
- Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
- Progesterone-receptor-positive Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Dose Escalation and Dose Expansion
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- Randomized for the Expansion Phase
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Dose Escalation |
Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3964 at increasing dosage levels to determine the MTD and/or preliminary RDEs. |
|
Experimental Dose Expansion |
Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
Lake Mary 4161373, Florida 4155751 32746
Boston 4930956, Massachusetts 6254926 02215
Hackensack 5098706, New Jersey 5101760 07601
Philadelphia 4560349, Pennsylvania 6254927 19107
Sarah Cannon Research Institute
844-482-4812
Nashville 4644585, Tennessee 4662168 37203
Austin 4671654, Texas 4736286 78758
Salt Lake City 5780993, Utah 5549030 84145
More Details
- NCT ID
- NCT06586957
- Status
- Recruiting
- Sponsor
- NiKang Therapeutics, Inc.
Detailed Description
Inclusion Criteria: - Must have a pathologically confirmed, advanced and unresectable or metastatic solid tumor listed below with documented disease progression on last standard treatment. For Part 1 only: Patients must be refractory to, or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. Part 1 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 Part 2 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 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) 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. - Measurable disease per RECIST v1.1, except for subjects with HR+/HER2- breast cancer or endometrial cancer (Part 1) who must have measurable or evaluable (including skin or bone lesion only) disease. - Age ≥18 years - ECOG PS 0-1 - Have adequate organ function - Subjects with female reproductive organs must be surgically sterile, post-menopausal, or, if of child-bearing potential, must meet pre-specified criteria - Subjects who are capable of insemination must meet pre-specified criteria - Ability to swallow oral medications. - Consent to provide archived tumor tissues and paired tumor biopsy at pretreatment and on-treatment. 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 - Clinically 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