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

NiKang Therapeutics

Status and phase

Enrolling

Phase 1

Conditions

Solid Tumor

Advanced Ovarian Carcinoma

Ovarian Neoplasms

Small Cell Lung Cancer

Advanced Solid Tumor

Triple Negative Breast Neoplasms

Ovarian Carcinoma

Metastatic Ovarian Carcinoma

CCNE1 Amplification

Platinum-resistant Ovarian Cancer

Hormone Receptor Negative Breast Carcinoma

Metastatic Endometrial Cancer

Solid Tumor, Adult

Progesterone-receptor-positive Breast Cancer

Platinum-refractory Ovarian Carcinoma

Small Cell Lung Carcinoma

Metastatic Gastric Carcinoma

Ovarian Cancer

Endometrial Neoplasms

Metastatic Tumor

Gastric Cancer

Advanced Endometrial Carcinoma

Metastatic Endometrial Carcinoma

Endometrial Diseases

Advanced Gastric Carcinoma

Metastatic Gastric Cancer

Triple Negative Breast Cancer

Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Treatments

Drug: NKT3964

Study type

Interventional

Funder types

Industry

Identifiers

NCT06586957

NKT3964-101

Details and patient eligibility

About

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).

Full 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:

Ovarian cancer with CCNE1 amplification
Endometrial cancer with CCNE1 amplification
Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
Small cell lung cancer (SCLC)
Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
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])
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

Enrollment

150 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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:

Ovarian cancer with CCNE1 amplification
Endometrial cancer with CCNE1 amplification
Gastric, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
Small cell lung cancer (SCLC)
Triple-negative breast cancer (TNBC; HER2, estrogen receptor and progesterone receptor negative)
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])
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.

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

150 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: NKT3964

Dose Expansion

Experimental group

Description:

Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D.

Treatment:

Drug: NKT3964