TAS0728 / Otsuka - LARVOL DELTA

Phase I Study of TAS0728 in Patients with Advanced Solid Tumors with HER2 Aberration (TAIBRAKHER Study) (SABCS 2025) - "Therefore, the genotypes for ABCG2, which encode a BCRP, are evaluated as a candidate factor for interpatient variability of pharmacokinetics. HER2 gene status is also analyzed from circulating tumor DNA in blood at baseline and disease progression."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ABCG2 • HER-2

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1 | N=19 | Terminated | Sponsor: Taiho Oncology, Inc. | Phase classification: P1/2 ➔ P1

Metastases • Phase classification • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • ERBB3 • HER-2

Treatment outcomes in previously treated patients with advanced/metastatic HER2+ biliary tract cancer: A systematic review (ESMO-GI 2024) - "Nine therapies (pertuzumab + trastuzumab [P+T], pyrotinib, SHR-A1811, TAS0728, T-deruxtecan [T-DXd], tebotelimab + margetuximab, T+FOLFOX [T+F], tucatinib + T and zanidatamab [zani]) were assessed... HER2 targeted therapies demonstrated promising benefit in patients with previously treated advanced/metastatic HER2+ BTC."

Clinical • Metastases • Review • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Role of individual HER family members and pan-HER targeting treatment strategy in NRG1 fusion positive cancer (AACR 2023) - "Our data indicated that pan-HER tyrosine kinase inhibitors (TKIs), such as poziotinib, were more effective at blocking HER2/HER3, EGFR/HER3 and HER4 signaling in NRG1-fusion expressing cells as compared to TKIs with greater relative specificity for EGFR (erlotinib, lapatinib), HER2 (pyrotinib), EGFR/HER2 (afatinib, dacomitinib, neratinib) or HER2/HER4 (TAS0728,tucatinib). Treatment with cetuximab, an antibody that targets EGFR, in combination with trastuzumab and pertuzumab yielded a synergistic effect on tumor cell killing. These data indicate that HER4 and EGFR can play a role in NRG1 fusion-driven signaling through crosstalk with HER2/HER3 and thus, pan-HER/EGFR inhibitors are more effective than EGFR/HER2 or HER2/HER4-selective inhibitors, highlighting the therapeutic potential of targeting multiple members of the HER family in NRG1 fusion driven cancers."

Clinical • Oncology • ERBB3 • ERBB4 • NRG1

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2 | N=19 | Terminated | Sponsor: Taiho Oncology, Inc. | Active, not recruiting ➔ Terminated; The study was stopped due to unacceptable toxicity during the dose-escalation portion (Phase 1) of the study and did not progress to Phase 2

Trial termination • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

Proteins Interacting with S-Nitrosoglutathione reductase to Regulate Nitric Oxide Homeostasis. (PubMed, FASEB J) - "20: 786-802 (2008). doi: 10.1105/tpc/107.052647."

Journal • CAT

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Trial completion date: Dec 2021 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Trial completion date: Aug 2021 ➔ Dec 2021; Trial primary completion date: Aug 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

A first-in-human phase I study of TAS0728, an oral covalent binding inhibitor of HER2, in patients with advanced solid tumors with HER2 or HER3 aberrations. (PubMed, Invest New Drugs) - P1/2 | "The study was stopped due to unacceptable toxicity during the dose-escalation as the overall risk-benefit ratio no longer favored the dose level being tested, therefore the MTD was not determined. ClinicalTrials.gov registration number: https://clinicaltrials.gov/ct2/show/NCT03410927 ; registered on January 25, 2018."

Clinical • Journal • P1 data • Cardiovascular • Immunology • Oncology • Solid Tumor • ERBB3 • HER-2

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Trial completion date: Jun 2020 ➔ Jan 2021; Trial primary completion date: Jun 2020 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

Acquired resistance to trastuzumab/pertuzumab or to T-DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728. (PubMed, Cancer Sci) - "HER2-targeting antibodies (trastuzumab, pertuzumab) and a HER2-directed antibody-drug conjugate (trastuzumab emtansine: T-DM1) are used for the treatment of HER2-overexpressing breast cancer. These results suggest that tumors with acquired resistance to trastuzumab and pertuzumab and to T-DM1 are still dependent on oncogenic HER2-HER3 signaling and are vulnerable to HER2 signal inhibition by TAS0728. These results provide a rationale for TAS0728 therapy for breast cancers that are refractory to established anti-HER2 therapies."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

TAS0728, a covalent-binding, HER2-selective kinase inhibitor shows potent antitumor activity in preclinical models. (PubMed, Mol Cancer Ther) - P1/2; "Taken together, our results demonstrated that TAS0728 may offer a promising therapeutic option with improved efficacy as compared to current HER2 inhibitors for HER2-activated cancers. Assessment of TAS0728 in ongoing clinical trials is awaited (NCT03410927)."

Journal • Preclinical

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Trial completion date: Dec 2019 ➔ Jun 2020; Trial primary completion date: Dec 2019 ➔ Jun 2020

Clinical • Trial completion date • Trial primary completion date • HER-2

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Trial completion date: Aug 2019 ➔ Dec 2019; Trial primary completion date: Aug 2019 ➔ Dec 2019

Clinical • Trial completion date • Trial primary completion date

Acquired resistance to trastuzumab/pertuzumab, or to T-DM1 in vivo can be overcome by HER2 inhibition with TAS0728 (AACR-NCI-EORTC 2019) - "Background: HER2-targeting antibodies (trastuzumab, pertuzumab) and an antibody-drug conjugate (trastuzumab emtansine: T-DM1) are available for the treatment of HER2 overexpressed breast cancer. The acquired resistance models to trastuzumab/pertuzumab or T-DM1 were established in vivo. Selective inhibition of HER2 kinase by TAS0728 is effective in the both resistant models. These results provide a rationale for therapy with TAS0728 in patients refractory to the established anti-HER2 therapy."

Preclinical

A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov) - P1/2; N=19; Active, not recruiting; Sponsor: Taiho Oncology, Inc.; Recruiting ➔ Active, not recruiting; N=204 ➔ 19; Trial completion date: Sep 2021 ➔ Aug 2019; Trial primary completion date: Mar 2021 ➔ Aug 2019

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date