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

April 10, 2024 updated by: NiKang Therapeutics, Inc.

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 + 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.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Sarah Cannon Research Institute at HealthONE
        • Principal Investigator:
          • Gerald Falchook, MD, MS
        • Contact:
          • Kelly Mozzetta
    • Florida
      • Celebration, Florida, United States, 34747
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • The Gabrail Pharmacology Phase 1 Research Center
        • Principal Investigator:
          • Nashat Y Gabrail, MD
        • Contact:
    • Texas
      • Austin, Texas, United States, 78758
        • Recruiting
        • Texas Oncology-Austin Midtown NEXT Oncology
        • Principal Investigator:
          • Andrae Vandross, MD
        • Contact:
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
        • Contact:
        • Principal Investigator:
          • Justin A Call, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
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.
Drug: NKT3447
Oral CDK2 inhibitor
Experimental: Dose Expansion
Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D.
Drug: NKT3447
Oral CDK2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Dose Limiting Toxicity (DLT) events
Time Frame: 28 days
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
28 days
Objective Response Rate (ORR)
Time Frame: 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 2 years
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
Overall Survival (OS)
Time Frame: 2 years
OS defined as the time from the date the participant started study drug to death for any reason.
2 years
Number of Participants with Adverse Events
Time Frame: 2 years
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
Duration of Response (DOR)
Time Frame: 2 years
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
Disease control rate
Time Frame: 1 year
Disease control rate defined as CR + PR + stable disease [SD]
1 year
Time to Response (TTR)
Time Frame: 1 year
TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.
1 year
Maximum observed plasma concentration (Cmax) of NKT3447
Time Frame: 1 month
Maximum observed plasma concentration (Cmax) of NKT3447
1 month
Time to maximum observed plasma concentration of NKT3447 (Tmax)
Time Frame: 1 month
Time to maximum observed plasma concentration of NKT3447 (Tmax)
1 month
Observed trough concentration of NKT3447 (Ctrough)
Time Frame: 88 weeks
Observed trough concentration of NKT3447 (Ctrough)
88 weeks
Area under the plasma concentration-time curve (AUC0-t) of NKT3447
Time Frame: 1 month
Area under the plasma concentration-time curve (AUC0-t) of NKT3447
1 month
Apparent clearance (CL/F)
Time Frame: 1 month
Apparent clearance (CL/F)
1 month
Apparent volume of distribution (V/F)
Time Frame: 1 month
Apparent volume of distribution (V/F)
1 month
Half-life (t1/2)
Time Frame: 1 month
Half-life (t1/2)
1 month
Accumulation ratio (AR)
Time Frame: 1 month
Accumulation ratio (AR)
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NiKang Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

May 1, 2025

Study Registration Dates

First Submitted

February 9, 2024

First Submitted That Met QC Criteria

February 9, 2024

First Posted (Actual)

February 20, 2024

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKT3447-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD are not planned to be shared at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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