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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Solid Tumor, Glioblastoma, Non-small Cell Lung Cancer, Breast Cancer

Intervention / Treatment
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* Drug: TAS2940
* Drug: TAS2940


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS2940 Dose Escalation<br>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<br>* Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.<br>|
| Experimental: Dose Expansion Non-small Cell Lung Cancer<br>Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations | Drug: TAS2940<br>* Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.<br>|
| Experimental: Dose Expansion Breast Cancer<br>Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations | Drug: TAS2940<br>* Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.<br>|
| Experimental: Dose Expansion Gliblastoma<br>Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations. | Drug: TAS2940<br>* Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.<br>|
| Experimental: Dose Expansion Solid tumors<br>Dose expansion will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations. | Drug: TAS2940<br>* Study subjects with select solid tumors characterized by EGFR or HER2 aberrations will receive TAS2940 at the dose identified during Dose Escalation phase.<br>|

What is the study measuring?
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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 |