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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-19

Study Completion Date

2029-05-31

Brief Summary

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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).

Detailed Description

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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 and Food Effect Sub-study:

1. Ovarian cancer
2. Endometrial cancer (only 'endometrioid' subtype requires 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.

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 (only endometrioid subtype will require 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. 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

Conditions

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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

Keywords

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CDK 2 Inhibitor CDK 4 Inhibitor CDK 6 Inhibitor CDK2 Degrader Protein Degrader PROTAC

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose Escalation and Dose Expansion

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Randomized for the Expansion Phase

Study Groups

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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.

Group Type EXPERIMENTAL

NKT3964

Intervention Type DRUG

Oral CDK2 Degrader

Dose Expansion

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

Group Type EXPERIMENTAL

NKT3964

Intervention Type DRUG

Oral CDK2 Degrader

Interventions

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NKT3964

Oral CDK2 Degrader

Intervention Type DRUG

Eligibility Criteria

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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
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

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.

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 (only 'endometrioid' subtype will require 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. 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

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Sponsor Contact

Role: CONTACT

Phone: (302) 596-8654

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

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Dose Escalation

NKT3964

Dose Expansion

NKT3964

Interventions

NKT3964

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

NiKang Therapeutics, Inc.

Responsible Party

Locations

University of Arkansas Medical School

University of California - Los Angeles

UCSF

SCRI at HealthOne

Florida Cancer Specialists & Research Institute

AdventHealth Cancer Institute

Emory Winship Cancer Institute

Augusta University

University of Kansas

Dana Farber Cancer Institute

John Theurer Cancer Center at Hackensack UMC

Sidney Kimmell Cancer Center - Jefferson Health

UPMC

Sarah Cannon Research Institute (SCRI)

NEXT Oncology

UT Southwestern

Intermountain Health

University of Virginia

NEXT Virginia

Countries

Central Contacts

Sponsor Contact

Facility Contacts

Maroof Zafar, MD

Front Desk

Aimee Jackson

Winship Referrals

Elizabeth Lee, MD

Oncology Clinical Research Referral Office

Sarah Cannon Research Institute

Kate Hall

Suhrutha Bushan

Joshua Kunz, MD

Chrystal Axford

Maybelle De La Rosa

Other Identifiers

NKT3964-101