A Study of TAS-116 in Patients With Solid Tumors

Study Overview
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Brief Summary
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A First-in-Human (FIH) study of TAS-116 in patients with advanced solid tumors was first initiated in Japan in April 2014 and has been ongoing since then. The study consists of a dose escalation phase and a dose expansion phase. Three dosing regimens of TAS-116, once daily (QD), every other day (QOD) and 5 days on/2 days off regimens in 21-day cycles, are being evaluated. This phase I study is also planned to enroll patients with advanced solid tumors in UK to confirm the MTD, safety, tolerability, and pharmacokinetics of TAS-116 in a Western patient population in the dose expansion phase. In addition, patients with HER2+ MBC, NSCLC harboring EGFR mutations or NSCLC harbouring ALK translocations will be further evaluated for safety, tolerability, and efficacy in 3 separate cohorts at recommended dose of TAS-116 on the 5 days on/2 days off regimen.

Official Title
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A Phase IA/IB Study Evaluating TAS-116 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: TAS-116


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females with an age ≥ 18 years (≥ 20 years in Japan) Patients with histological- or cytological-confirmed, advanced unresectable breast, gastric, or non-small cell lung cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists. a. Part C: Only the following subtype of tumors with the molecular/genetic alterations will be enrolled: HER2 positive MBC Advanced NSCLC, harboring EGFR mutations after progression on osimertinib Advanced NSCLC, harboring ALK translocations after treatment with alectinib or at least 2 ALK inhibitors Has At least one measurable lesion as defined by RECIST criteria Is able to take medications orally (e.g., no feeding tube). Is able to agree to and sign informed consent and to comply with the protocol Has adequate organ function Exclusion Criteria: Has a serious illness or medical condition(s) Has received treatment with any prescribed treatments within specified time frames prior to study drug administration Significant ophthalmologic abnormality, Impaired cardiac function or clinically significant cardiac disease

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-116<br> | Drug: TAS-116<br>* TAS-116 is an oral heat shock protein 90 (HSP90) inhibitor investigated in 3 dosing regimens (QD, QOD, 5 days on 2 days off) in patients with advanced solid tumor and then at one dose schedule in advanced breast and lung cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing Dose Limiting Toxicity graded according to CTCAE Version 4.03, observed in the Cycle 1 in order to meet the objective of assessment of the MTD of TAS-116 (Part A) |  | 21 days in Cycle 1 | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Parts A, B and C) |  | Safety monitoring will begin at the informed consent obtained and continue up to 28 days after the last dose of TAS-116 or until new anti-tumor therapy, whichever is earlier. | 
| Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Part C) |  | Up to 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) after administration of TAS-116 (Parts A and B) |  | 21 days in Cycle 1 | 
| Area under the plasma drug concentration-time curve (AUC) after administration of TAS-116 (Parts A and B) |  | 21 days in Cycle 1 | 
| Disease Control Rate using RECIST 1.1 (Parts A, B, and C) |  | Up to last participant completes at least 6 months | 
| Duration of Response (Part C) |  | Up to last participant completes at least 6 months | 
| Progression Free Survival (Part C) |  | Up to last participant completes at least 6 months | 
| Overall Survival |  | Up to last participant completes at least 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Solid Tumors, Pharmacokinetics, Pharmacodynamics, MTD, TAS116, HSP90 Inhibitor, Neoplasms, HER2 positive MBC, NSCLC EGFR, NSCLC ALK positive