TAS0728 in Solid Tumours with HER2 or HER3 Abnormalities
Research type
Research Study
Full title
A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY TO INVESTIGATE THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF TAS0728, AN ORAL COVALENT BINDING INHIBITOR OF HER2, IN SUBJECTS WITH ADVANCED SOLID TUMORS WITH HER2 OR HER3 ABNORMALITIES
IRAS ID
238963
Contact name
Gemma Sheppard
Contact email
Sponsor organisation
Taiho Oncology, Inc.
Eudract number
2017-004415-39
Clinicaltrials.gov Identifier
IND Number, 137403
Duration of Study in the UK
4 years, 0 months, 1 days
Research summary
Research Summary
This is a 2-part, Phase 1/2, open-label, multicentre study design to evaluate the safety, tolerability, PK, pharmacodynamic, PGx, and efficacy of TAS0728. This study consists of Phase 1 and Phase 2a, components in male and female participants over the age of 18 with advanced solid tumours with HER2 or HER3 abnormalities or mutation who have progressed despite standard therapy or for which no standard therapy exists.
Targeting the human epidermal growth receptor (HER)2 protein has proven an effective anti-tumour strategy. HER2 and HER3 are similar structurally although are activated differently. TAS0728 is a potent and selective covalent binding inhibitor with enhanced specificity in preclinical studies against both amplified and mutated HER2.
This will be the first time TAS0728 will be tested in humans.
The study includes 2 phases, dose-escalation and dose-expansion.
- In the dose-escalation phase there are approximately 8 different doses of TAS0728 that will be administered. Approximately 40 participants will be enrolled in this phase of the study. The first set of participants will receive the lowest dose and if TAS0728 does not cause significant side effects, the dose will be increased to the next set of participants. The dose will continue to increase for every new group of participants.
- In the dose-expansion phase, participants will receive the TAS0728 that was tolerated in the dose escalation phase. Approximately 100 participants will be enrolled in this phase of the study.Up to 140 people will be asked to participate in the study in up to 80 clinical research sites globally.
Participants will be in treatment for approximately 9 months. This may be shorter or longer depending on how the participant tolerates the treatment.
The study is organised and funded by the sponsor of this study, Taiho Oncology, Inc.
Summary of Results
Although evaluation of efficacy was not a primary objective of the dose escalation portion of this study, some evidence of clinical benefit was obtained; this included 2 partial responses among 14 patients evaluable for best overall response. However, considering the toxicity profile discussed above, and taking into account the fatal AE of cardiac arrest considered possibly related to TAS0728, the Sponsor determined that the overall risk-benefit ratio no longer favored continuation of the study.
Note: page 55 from CSRREC name
London - Harrow Research Ethics Committee
REC reference
18/LO/0332
Date of REC Opinion
24 Apr 2018
REC opinion
Further Information Favourable Opinion