A Study of TAS-116 in Patients With Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: TAS-116

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Policlinico S.Orsola-Malpighi, U.O. Oncologia Medica
  • Catania, Italy, 95123
    • Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele Oncologia Medica
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia , Sviluppo di Nuovi Farmaci per Terapie Innovative
  • Roma, Italy, 00144
    • Regina Elena National Cancer Institute
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • London, United Kingdom, SE19 9RT
    • Division of Cancer Studies, Kings College London
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust Institute of Cancer Sciences, University of Manchester
  • Sutton, United Kingdom, SM2 5PTT
    • Royal Marsden
  • England
    • Newcastle Upon Tyne, England, United Kingdom
      • Northern Centre for Cancer Care
• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System, Institute for Translational Oncology Research
  • Virginia
    • Fairfax, Virginia, United States, 86885
      • US Oncology - Virginia Cancer Specialists, P.C.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or females with an age ≥ 18 years (≥ 20 years in Japan)

2. 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

3. Has At least one measurable lesion as defined by RECIST criteria
4. Is able to take medications orally (e.g., no feeding tube).
5. Is able to agree to and sign informed consent and to comply with the protocol
6. Has adequate organ function

Exclusion Criteria:

1. Has a serious illness or medical condition(s)
2. Has received treatment with any prescribed treatments within specified time frames prior to study drug administration
3. Significant ophthalmologic abnormality,
4. Impaired cardiac function or clinically significant cardiac disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAS-116	Drug: TAS-116; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Actual): May 3, 2019
• Study Completion (Actual): May 3, 2019

Study Registration Dates

• First Submitted: November 10, 2016
• First Submitted That Met QC Criteria: November 14, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Neoplasms; Pharmacokinetics; Phase I; Solid Tumors; Pharmacodynamics; MTD; HSP90 Inhibitor; TAS116; HER2 positive MBC; NSCLC EGFR; NSCLC ALK positive
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TAS-116-101; 10058010 (Other Identifier: Taiho Oncology, Inc.); 2015-005328-24 (EudraCT Number)

Drug and device information, study documents

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