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

Ovarian Cancer Clinical Trial

Official title:

A Phase 1, First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, PK, and Preliminary Anti-tumor Activity of the Novel Orally Available CDK2 Inhibitor NKT3447 in Adults With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06264921
• Other study ID #: NKT3447-101
• Status: Recruiting
• Phase: Phase 1
• Start date: February 23, 2024
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: NiKang Therapeutics, Inc.
• Contact: Sponsor Contact
• Phone: 3024155127
• Email: clinicaltrials[@]nikangtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: May 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Endometrial Carcinoma
• Advanced Gastric Carcinoma
• Advanced Ovarian Carcinoma
• Advanced Solid Tumor
• Breast Neoplasms
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Endometrial Cancer
• Endometrial Diseases
• Endometrial Neoplasms
• Gastric Cancer
• Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
• Metastatic Endometrial Cancer
• Metastatic Endometrial Carcinoma
• Metastatic Gastric Cancer
• Metastatic Gastric Carcinoma
• Metastatic Ovarian Carcinoma
• Metastatic Tumor
• Neoplasm Metastasis
• Neoplasms
• Ovarian Cancer
• Ovarian Carcinoma
• Ovarian Neoplasms
• Platinum-refractory Ovarian Carcinoma
• Platinum-resistant Ovarian Cancer
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer
• Solid Tumor
• Solid Tumor, Adult
• Stomach Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Uterine Diseases

Intervention

Drug:
• NKT3447
Oral CDK2 inhibitor

Locations

Country	Name	City	State
United States	Texas Oncology-Austin Midtown NEXT Oncology	Austin	Texas
United States	The Gabrail Pharmacology Phase 1 Research Center	Canton	Ohio
United States	AdventHealth Cancer Institute	Celebration	Florida
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
NiKang Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose Limiting Toxicity (DLT) events	DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.	28 days
Primary	Objective Response Rate (ORR)	ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by the Investigator	1 year
Secondary	Progression-free survival (PFS)	PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression or death.	2 years
Secondary	Duration of Response (DOR)	Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first.	2 years
Secondary	Disease control rate	Disease control rate defined as CR + PR + stable disease [SD]	1 year
Secondary	Overall Survival (OS)	OS defined as the time from the date the participant started study drug to death for any reason.	2 years
Secondary	Time to Response (TTR)	TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.	1 year
Secondary	Number of Participants with Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.	2 years
Secondary	Maximum observed plasma concentration (Cmax) of NKT3447	Maximum observed plasma concentration (Cmax) of NKT3447	1 month
Secondary	Time to maximum observed plasma concentration of NKT3447 (Tmax)	Time to maximum observed plasma concentration of NKT3447 (Tmax)	1 month
Secondary	Observed trough concentration of NKT3447 (Ctrough)	Observed trough concentration of NKT3447 (Ctrough)	88 weeks
Secondary	Area under the plasma concentration-time curve (AUC0-t) of NKT3447	Area under the plasma concentration-time curve (AUC0-t) of NKT3447	1 month
Secondary	Apparent clearance (CL/F)	Apparent clearance (CL/F)	1 month
Secondary	Apparent volume of distribution (V/F)	Apparent volume of distribution (V/F)	1 month
Secondary	Half-life (t1/2)	Half-life (t1/2)	1 month
Secondary	Accumulation ratio (AR)	Accumulation ratio (AR)	1 month