Clinical trial NCT06264921: A Study With NKT3447 for Adults With Advanced/Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Solid Tumor, Adult
Advanced Solid Tumor
Metastatic Tumor
Ovarian Cancer
Ovarian Neoplasms
Ovarian Carcinoma
Metastatic Ovarian Carcinoma
Endometrial Cancer
Endometrial Neoplasms
Endometrial Diseases
Metastatic Endometrial 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 Cancer
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: CDK 2 Inhibitor
CDK 4 Inhibitor
CDK 6 Inhibitor
Lead sponsor: NiKang Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-02-20
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation and Dose Expansion
Primary purpose: TREATMENT

Brief 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).

Detailed 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 positive (ER+/PR+), 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 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.

Eligibility criteria: 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.

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

Dose Escalation(Part 1):

1. Ovarian cancer
2. Endometrial cancer
3. Gastric cancer or gastroesophageal junction cancer
4. Small cell lung cancer (SCLC)
5. Triple-negative breast cancer (human epidermal growth factor receptor 2 \[HER2\], estrogen receptor \[ER\], progesterone receptor negative)
6. ER/progesterone-receptor positive, HER2 negative 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 NGS by local liquid or tissue biopsy.

Dose Expansion (Part 2):

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 CCNE1 amplification as determined by NGS by local liquid or tissue biopsy.

* Measurable disease per the RECIST v1.1
* An Eastern Cooperative Oncology Group (ECOG) 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 with life-threatening complications, 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
* Major surgery within 2 months or minor surgery within 10 days before the first dose of NKT3447

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicity (DLT) events
timeFrame: 28 days
measure: Objective Response Rate (ORR)
timeFrame: 1 year
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Duration of Response (DOR)
timeFrame: 2 years
measure: Disease control rate
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Time to Response (TTR)
timeFrame: 1 year
measure: Number of Participants with Adverse Events
timeFrame: 2 years
measure: Maximum observed plasma concentration (Cmax) of NKT3447
timeFrame: 1 month
measure: Time to maximum observed plasma concentration of NKT3447 (Tmax)
timeFrame: 1 month
measure: Observed trough concentration of NKT3447 (Ctrough)
timeFrame: 88 weeks
measure: Area under the plasma concentration-time curve (AUC0-t) of NKT3447
timeFrame: 1 month
measure: Apparent clearance (CL/F)
timeFrame: 1 month
measure: Apparent volume of distribution (V/F)
timeFrame: 1 month
measure: Half-life (t1/2)
timeFrame: 1 month
measure: Accumulation ratio (AR)
timeFrame: 1 month
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Celebration
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia Cancer Center
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute - Broadway
state: Kentucky
city: Canton
country: United States
facility: The Gabrail Pharmacology Phase 1 Research Center
state: Ohio
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown NEXT Oncology
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
Study officials:
References: