A Study With NKT3447 for Adults With Advanced/Metastatic Solid Tumors

NiKang Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor; Advanced Ovarian Carcinoma; Ovarian Neoplasms; Advanced Solid Tumor; Triple Negative Breast Neoplasms; Ovarian Carcinoma; Metastatic Ovarian Carcinoma; CCNE1 Amplification; Platinum-resistant Ovarian Cancer; Endometrial Cancer; Hormone Receptor Negative Breast Carcinoma; Metastatic Endometrial Cancer; Small-cell Lung 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; Triple Negative Breast Cancer; Metastatic Gastric Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Treatments: Drug: NKT3447

Study type: Interventional

Funder types: Industry

Identifiers

NCT06264921

NKT3447-101

Details and patient eligibility

About

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) to determine the maximum tolerated dose (MTD) and/or preliminary recommended dose for expansion (RDE) of NKT3447 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), and the preliminary antitumor activity of NKT3447 in adult subjects with cyclin E1 (CCNE1) amplified ovarian cancer at the RDEs selected in Dose Escalation and to determine the preliminary recommended phase 2 dose (RP2D).

Full description

This is a Phase 1/1b, first-in-human, open-label, multicenter study of NKT3447 in adults with advanced/ metastatic solid tumors. The study consists of 2 parts, a Dose Escalation phase and a Dose Expansion phase. Eligible patients must have confirmed advanced/metastatic solid tumors (as outlined below) with disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment likely to improve the disease outcome in the judgment of the investigator.

Dose Escalation:

1. Ovarian cancer
2. Endometrial cancer
3. Gastric cancer or gastroesophageal junction cancer
4. Small cell lung cancer
5. Triple-negative breast cancer (human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor negative)
6. Estrogen receptor/progesterone-receptor + human epidermal growth factor receptor 2 negative (HER2-) breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and not suitable for endocrine therapy)
7. Other solid tumors with CCNE1 amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, or next generation sequencing by local liquid or tissue biopsy.

Dose Expansion:

a. Platinum resistant or refractory ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least 1 platinum containing therapy with cyclin E amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, or next-generation sequencing by local liquid or tissue biopsy.

The Dose Escalation phase will evaluate the safety, tolerability, and pharmacokinetics (PK) to determine the maximum tolerated dose (MTD) and/or preliminary recommended dose for expansion (RDE) of NKT3447 in adults with advanced or metastatic solid tumors.

The Dose Expansion phase will evaluate the safety, tolerability, pharmacokinetics (PK), and the preliminary antitumor activity of NKT3447 in adult subjects with CCNE1 amplified ovarian cancer at the RDEs selected in Dose Escalation and to determine the preliminary recommended RP2D.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must have confirmed unresectable advanced/metastatic solid tumors (as outlined below) with disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment likely to improve the disease outcome in the judgment of the investigator.

Dose Escalation:

1. Ovarian cancer
2. Endometrial cancer
3. Gastric cancer or gastroesophageal junction cancer
4. Small cell lung cancer
5. Triple-negative breast cancer (human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor negative)
6. Estrogen receptor/progesterone-receptor + human epidermal growth factor receptor 2 negative (HER2-) breast cancer (must have progressed following treatment with a CDK4/6 inhibitor, and not suitable for endocrine therapy)
7. Other solid tumors with CCNE1 amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, or next generation sequencing by local liquid or tissue biopsy.

Dose Expansion:

a. Platinum resistant or refractory ovarian cancer (defined as recurrence ≤6 months after completing platinum-based regimen) with progression on at least 1 platinum containing therapy with cyclin E amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, or next-generation sequencing by local liquid or tissue biopsy.

• Measurable disease per the RECIST v1.1
• An Eastern Cooperative Oncology Group performance status of 0 to 1
• Able to swallow oral medications.

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
• Visceral crisis, lymphangitic spread, CNS metastasis and/or carcinomatous meningitis
• Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade ≤ 1 severity (per CTCAE)
• Clinically active interstitial lung disease
• History of uveitis, retinopathy or other clinically significant retinal disease
• Has known human immunodeficiency virus (HIV), active hepatitis B or C infection
• Prior CDK2 inhibitor, WEE1 inhibitor, or protein kinase membrane associated tyrosine/threonine 1 inhibitor.
• Major surgery within 2 months or minor surgery within 10 days before the first dose of NKT3447

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

90 participants in 2 patient groups

Dose Escalation

Experimental group

Description:

Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3447 at increasing dosage levels to determine the MTD and/or preliminary RDEs.

Treatment:

Drug: NKT3447

Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: NKT3447