A Study of TAS3351 in NSCLC Patients With EGFRmt

Study Overview
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Brief Summary
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This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation.

Detailed Description
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This study will be conducted in 3 parts (i.e. dose escalation, dose expansion, and a phase 2 portion). The dose escalation part will investigate the safety and determine the recommended phase 2 dose and the recommended dosing regimen of TAS3351 administered orally. The dose expansion part will explore the efficacy of TAS3351 in NSCLC patients with C797S EGFR mutations. The phase 2 part will assess the efficacy of TAS3351 in NSCLC patients with C797S EGFR mutations.

Official Title
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A Phase 1/2 Study of TAS3351 in Patients With Advanced Non-Small Cell Lung Cancer and EGFR Mutations

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: TAS3351 oral administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced, non-resectable or metastatic NSCLC Have adequate organ function Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Has tumor tissue available to allow for analysis of EGFRmt status Dose Escalation: • Has any EGFRmt status Dose Escalation back-fill part, Dose Expansion and Phase II: Has any sensitizing EGFRmt and a confirmed C797S EGFRmt Has measurable disease per RECIST v1.1 Exclusion Criteria: Participating in medical research not compatible with this study Symptomatic and unstable CNS metastases Have not recovered from prior cancer treatment Have a significant cardiac condition Are a pregnant or breastfeeding female A serious illness or medical condition Unable to swallow or digest pills

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS3351 Part A (Dose Escalation)<br>Dose escalation will assess the safety and determine the recommended phase 2 dose and regimen of TAS3351 administered orally. | Drug: TAS3351 oral administration<br>* TAS3351 will be administered orally<br>|
| Experimental: TAS3351 Part B (Dose Expansion)<br>TAS3351 in NSCLC patients with C797S EGFRmt. TAS3351 will be administered at the recommended phase 2 dose determined in Part A. | Drug: TAS3351 oral administration<br>* TAS3351 will be administered orally<br>|
| Experimental: TAS3351 Part C (Phase 2)<br>To assess efficacy of TAS3351 in NSCLC patients with C797S EGFRmt. TAS3351 will be administered at the recommended phase 2 dose. | Drug: TAS3351 oral administration<br>* TAS3351 will be administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation: To investigate the safety and determine the recommended Phase 2 dose and dosing schedule of TAS3351 | Adverse Events | baseline through cycle 1(each cycle is 21 days) | 
| Dose Escalation: To investigate the safety and determine the recommended Phase 2 dose and dosing schedule of TAS3351 | Incidence of dose limiting toxicities (DLTs) | baseline through cycle 1(each cycle is 21 days) | 
| Dose Expansion: To explore the efficacy of TAS3351 | Objective Response Rate (ORR) | estimated 9 months | 
| Phase 2: To assess the efficacy of TAS3351 | Objective Response Rate (ORR) | estimated 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation:To evaluate the antitumor activity of TAS3351 | Objective response rate (ORR) | estimated 20 months | 
| Dose Escalation:To evaluate the antitumor activity of TAS3351 | Duration of response (DoR) | estimated 20 months | 
| Dose Escalation:To evaluate the antitumor activity of TAS3351 | Disease control rate (DCR) | estimated 20 months | 
| Dose Escalation: To evaluate the antitumor activity of TAS3351 | Progression free survival (PFS) | estimated 20 months | 
| Dose Escalation: To evaluate the antitumor activity of TAS3351 | Overall Survival (OS) | estimated 20 months | 
| Dose Escalation: To characterize the pharmacokinetics (PK) of TAS3351 | Evaluate the maximum plasma concentration (Cmax) | Cycle 1 Day 1 through cycle 1 Day 15 (21-Day cycle) | 
| Dose Escalation: To characterize the pharmacokinetics (PK) of TAS3351 | Area under the plasma concentration-time curve (AUC) | ECycle 1 Day 1 through cycle 1 Day 15 (21-Day cycle) | 
| Dose Expansion: To confirm the safety and tolerability of TAS3351 at the recommended phase 2 dose and dosing schedule | Adverse Events (AEs) | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Duration of response (DoR) by ICR | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Progression Free Survival (PFS) by ICR | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Disease Control Rate (DCR) by ICR | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Objective Response Rate (ORR) by Investigator Assessment | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Duration of Response (DoR) by Investigator Assessment | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Progression Free Survival (PFS) by Investigator Assessment | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Disease Control Rate (DCR) by Investigator Assessment | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Intracranial Objective Response Rate (icORR) | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Intracranial Duration of Response (icDOR) | estimated 9 months | 
| Dose Expansion: To further explore the anti-tumor efficacy of TAS3351 | Overall survival (OS) | estimated 9 months | 
| Phase 2: To evaluate the safety and tolerability of TAS3351 | Adverse Events (AEs) | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Duration of response (DoR) by ICR | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Progression Free Survival (PFS) by ICR | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Disease Control Rate (DCR) by ICR | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Objective Response Rate (ORR) by Investigator Assessment | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Duration of Response (DoR) by Investigator Assessment | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Progression Free Survival (PFS) by Investigator Assessment | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Disease Control Rate (DCR) by Investigator Assessment | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Intracranial Objective Response Rate (icORR) | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Intracranial Duration of Response (icDOR) | estimated 3 years | 
| Phase 2: To further assess the efficacy of TAS3351 | Overall survival (OS) | estimated 3 years | 
| Phase 2:To evaluate patient reported outcomes (PROs) | responses to patient questionnaires | estimated 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC, EGFR mutation, C797S mutation, TAS3351