A Study of TAS2940 in Participants With Locally Advanced or Metastatic Solid Tumor Cancer

A Phase 1 Study of TAS2940 in Patients With Locally Advanced or Metastatic Solid Tumors With EGFR and / or HER2 Aberrations

This is a first-in-human, open label, multicenter study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and the preliminary antitumor activity of TAS2940 in patients with advanced or metastatic solid tumors who are not candidates for approved or available therapies.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Glioblastoma; Solid Tumor; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: TAS2940; Drug: TAS2940

Detailed Description

TAS2940 is a small molecule inhibitor of ERBB family proteins HER2 and EGFR. It has not been evaluated in human subjects yet. The study will be conducted in 2 parts, dose escalation and dose expansion. The dose escalation part will assess the safety and determine the maximum tolerated dose, the recommended phase 2 dose and the recommended dosing regimen of TAS2940 administered orally. The dose expansion part will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Taiho Oncology, INC; Phone Number: 609-250-7336; Email: clinicaltrialinfo@taihooncology.com

Study Locations

• France
  • Cedex
    • Villejuif, Cedex, France, 94805
      • Recruiting
      • CLCC Gustave Roussy
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
      • Sub-Investigator: Katie Estopinal
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Contact: Phone Number: 713-563-0978; Email: mbeaujean@mdanderson.org
      • Sub-Investigator: Michele Beaujean

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have histologically confirmed solid cancer that is locally advanced and metastatic and available standard treatment options have been exhausted
• Have adequate organ function
• ECOG PS 0-1

Dose Escalation:

• Have measurable or non- measurable disease per RECIST criteria v1.1 or RANO
• Any solid tumor with EGFR and / or HER2 aberration

Dose Expansion:

• Have measurable disease per RECIST criteria v1.1 for solid tumor (excluding primary brain tumor) or RANO (for glioblastoma)
• Cohort A: Non-small cell lung cancer (NSCLC)
• Cohort B: HER2 positive breast cancer
• Cohort C: Recurrent or refractory glioblastoma
• Cohort D: Other solid tumors with EGFR or HER2 aberrations

Exclusion Criteria:

• Non-stable brain metastases
• Have significant cardiovascular disorder
• Have not recovered from prior cancer treatment
• A serious illness or medical condition

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAS2940 Dose Escalation; Dose escalation will assess the safety and determine the maximum tolerated dose, the recommended phase 2 dose and the recommended dosing regimen of TAS2940 administered orally.	Drug: TAS2940; Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.; Drug: TAS2940; Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.
Experimental: Dose Expansion Non-small Cell Lung Cancer; Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations	Drug: TAS2940; Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.; Drug: TAS2940; Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.
Experimental: Dose Expansion Breast Cancer; Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations	Drug: TAS2940; Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.; Drug: TAS2940; Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.
Experimental: Dose Expansion Gliblastoma; Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations.	Drug: TAS2940; Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.; Drug: TAS2940; Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.
Experimental: Dose Expansion Solid tumors; Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations.	Drug: TAS2940; Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.; Drug: TAS2940; Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation:Maximum Tolerated Dose (MTD)	Determine the incidence of dose-liming toxicities (DLTs) and adverse events (AEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 within the first cycle	One Month
Dose Expansion:Overall Response Rate	Document the ORR, defined as proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR) based on investigator accessed radiographic response per RECIST 1.1 or RANO criteria	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Overall Response Rate (ORR)	Document the ORR defined as proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR) based on investigator accessed radiographic response per RECIST 1.1 or RANO criteria	6 Months
Dose Escalation:Pharmacokinetic (PK) Profile	Evaluation of the maximum observed plasma concentration; time to reach maximum concentration, area under the Concentration-time curve and time it takes for plasma concentration to fall by half its original value (T1/2) of TAS2940	3 Months
Dose Expansion:Incidence of treatment-emergent Adverse Events (Safety and tolerability)	Safety and tolerability of TAS2940 based on reported AEs, graded according to NCI-CTCAE v.5.0	Estimated up to 6 months
Dose Expansion:Duration of Response (DOR)	DOR, defined as time from the first documentation of response to date of objective tumor progression or death due to any cause, whichever occurs first.	Estimated up to 6 months
Dose Expansion:Disease Control Rate (DCR)	DCR, defined as the proportion of patients experiencing a best overall response of Stable Disease (SD), PR or CR	Estimated up to 6 months
Dose Expansion:Progression Free Survival (PFS)	Date of PR or CR to date of objective progression or death due to any cause.	Estimated up to 6 months
Dose Expansion:Pharmacokinetic profile of TAS2940	Evaluation of the maximum observed plasma concentration; time to reach maximum concentration, area under the Concentration-time curve and time it takes for plasma concentration to fall by half its original value (T1/2) of TAS2940	3 Months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: TAS2940-101; 2021-002189-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No