bizrolertinib (RG6596) / Suzhou Zanrong, Roche - LARVOL DELTA

BREnnA: Phase II/III randomised study of ZN-A-1041 or tucatinib (TUC), in combination with trastuzumab + capecitabine (HX), in patients (pts) with HER2-positive locally advanced or metastatic breast cancer (HER2+ LA/mBC) with or without central nervous system (CNS) metastases (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P2/3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Safety and efficacy of ZN-A-1041, a highly blood-brain barrier (BBB)–permeable HER2 tyrosine kinase inhibitor (TKI), + trastuzumab deruxtecan (T-DXd) or pertuzumab-trastuzumab (PH) in HER2-positive metastatic breast cancer (HER2+ mBC): Phase Ic expansion results from the ZN-A-1041-101-US trial. (ASCO 2026) - P1/2 | "ZN-A-1041 showed manageable safety profiles and promising clinical activity when combined with standard anti-HER2 therapies in pts with HER2+ mBC, both with or without CNS metastases. High disease control in pts pretreated with T-DXd and notable continued responses in the PH maintenance setting support further clinical evaluation of these combinations. *Efficacy reported for 13 pts with measurable disease receiving maintenance therapy with ZN-A-1041 + PH after taxane + H ± P induction."

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

BReNNA: RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive (clinicaltrials.gov) - P2/3 | N=650 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2/3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

BReNNA: RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive (clinicaltrials.gov) - P2/3 | N=650 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Our ASCO data also highlight progress in HER2-positive breast cancer, an area Genentech has led for over 30 years (Genentech Press Release) - "RG6596/ZN-A-1041 in HER2-positive breast cancer: Preliminary results from a Phase Ic expansion trial will provide early information on the safety and efficacy of ZN-A-1041, a highly blood-brain barrier-permeable, HER2-selective tyrosine kinase inhibitor, in combination with other HER2-targeted therapies, for patients with pre-treated HER2-positive metastatic breast cancer."

P1 data • HER2 Positive Breast Cancer

A Study to Evaluate the Effect of Food and Proton Pump Inhibitor on the Pharmacokinetics of ZN-A-1041 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Genentech, Inc. | Recruiting ➔ Completed | N=48 ➔ 24 | Trial completion date: Aug 2026 ➔ Dec 2025 | Trial primary completion date: Aug 2026 ➔ Dec 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

WO46069: A Clinical Trial to Compare the Effectiveness and Safety of RO7771950 in Combination with Trastuzumab and Capecitabine, Versus Tucatinib in Combination with Trastuzumab and Capecitabine, in People with Locally Advanced or Metastatic Breast Cancer that is HER2-Positive (clinicaltrialsregister.eu) - P2/3 | N=107 | Not yet recruiting | Sponsor: F. Hoffmann-La Roche AG

New P2/3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Study to Evaluate the Effect of Food and Proton Pump Inhibitor on the Pharmacokinetics of ZN-A-1041 in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Genentech, Inc. | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date

Giredestrant, an oral selective estrogen receptor degrader, is central to its oncology portfolio. With pivotal data from the persevERA trial anticipated in 2026, the company prepares for potential global regulatory submissions. (GeneOnline) - "GlobalData projections indicate potential annual sales of $1.7 billion by 2031, though competition from AstraZeneca’s Camizestrant and Olema Pharmaceuticals’ Palazestrant is significant. Roche is also exploring combination approaches with Itovebi, GDC-4198, and ZN-1041 to differentiate its clinical outcomes. Ten pivotal Phase III readouts are expected in 2026, including the persevERA trial, which may influence Roche’s competitive position in the market."

Commercial • P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

A Study to Evaluate the Effect of Food and Proton Pump Inhibitor on the Pharmacokinetics of ZN-A-1041 in Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Genentech, Inc.

New P1 trial

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Oct 2026 ➔ Jul 2026 | Trial primary completion date: Oct 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Study to Evaluate the Relative Bioavailability of Two Tablet Formulations Compared to Capsule Formulation and the Effect of Food and Proton Pump Inhibitor on ZN-A-1041 Tablet(s) in Healthy Participants (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Genentech, Inc. | Recruiting ➔ Completed | N=66 ➔ 18 | Trial completion date: Oct 2025 ➔ Jul 2025 | Trial primary completion date: Oct 2025 ➔ Jul 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

ZN-1041-101: Trial of ZN-A-1041 Enteric Capsules in Patients With HER2-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=61 | Completed | Sponsor: Suzhou Zanrong Pharma Limited | Recruiting ➔ Completed

Trial completion • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=210 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Phase classification: P1 ➔ P1/2

Enrollment closed • Phase classification • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Study to Evaluate the Relative Bioavailability of Two Tablet Formulations Compared to Capsule Formulation and the Effect of Food and Proton Pump Inhibitor on ZN-A-1041 Tablet(s) in Healthy Participants (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Genentech, Inc.

New P1 trial

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

ZN-1041, a potential best-in-class BBB Penetrable HER2 Inhibitor, has high antitumor activity in patients with Breast Cancer with CNS Metastases.. (SABCS 2024) - P1 | "Encouraging preliminary efficacy and tolerability were observed for ZN-1041 either as monotherapy or combined with capecitabine and trastuzumab in TKI naïve, HER2+ BCBM patients. Further development of ZN-1041 combination therapies in a larger population is warranted, including the ongoing ZN-1041-101-US study which is evaluating the safety and efficacy of ZN-1041 in combination with trastuzumab deruxtecan and with trastuzumab and pertuzumab in a larger population across the US, EU, UK, Australia, and New Zealand."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Roche's new category 1 cancer drug to be included in breakthrough therapy designation [Google translation] (Sohu.com) - "Today (September 6), the official website of the Center for Drug Evaluation (CDE) of the China Food and Drug Administration just announced that the ZN-A-1041 enteric-coated capsules submitted by Suzhou Zanrong Pharmaceutical Technology Co., Ltd. are planned to be included in the breakthrough therapy category. The indications are: ZN-A-1041 combined with capecitabine and trastuzumab is used for patients with HER2-positive advanced brain metastasis breast cancer who have progressed on previous trastuzumab-containing treatment....According to the China Drug Clinical Trial Registration and Public Information Platform, two studies of ZN-A-1041 for HER2-positive advanced solid tumors are ongoing. One of the Phase 1 studies aims to evaluate the safety, tolerability, pharmacokinetics and efficacy of ZN-A-1041 enteric-coated capsules alone or in combination in patients with HER2-positive advanced solid tumors."

Breakthrough therapy • Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=210 | Recruiting | Sponsor: Suzhou Zanrong Pharma Limited | Trial completion date: Oct 2024 ➔ Oct 2026 | Trial primary completion date: Oct 2023 ➔ Oct 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=210 | Recruiting | Sponsor: Suzhou Zanrong Pharma Limited | Trial completion date: Nov 2023 ➔ Oct 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Trial of ZN-A-1041 Enteric Capsules in Patients With HER2-Positive Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Suzhou Zanrong Pharma Limited | Trial primary completion date: Dec 2022 ➔ Dec 2023

Metastases • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Preclinical and early clinical data of ZN-1041 in combination with trastuzumab deruxtecan to treat breast cancer with or without CNS metastases. (ASCO 2023) - P1 | " Anti-tumor activity of ZN-1041 alone or in combination with trastuzumab emtansine (TDM1), trastuzumab deruxtecan (TDXd), or trastuzumab (H) plus pertuzumab (P) was evaluated in BT474 BM orthotopic xenograft models...One pt with BCBM who was previously on tucatinib and TDXd had a confirmed PR... Safety and tolerability was observed for ZN-1041 with maximum tolerated dose 800 mg BID as monotherapy and combined with TDXd in pts with advanced HER2+ malignancies. Encouraging efficacy was observed in treatment-refractory settings. Additional safety and efficacy data of ZN-1041 in combination with TDM1, TDXd or HP are warranted."

Clinical data • Combination therapy • Preclinical • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Preclinical and early clinical data of ZN-1041, a best-in-class BBB penetrable HER2 inhibitor to treat breast cancer with CNS metastases. (ASCO 2023) - P1 | "ZN-1041 alone demonstrated dose-dependent and significant anti-tumor activity when compared to tucatinib in BM model. Encouraging efficacy and tolerability was observed for ZN-1041 monotherapy or combined with capecitabine and trastuzumab in TKI naïve, HER2+ BCBM patients. A Phase 2 pivotal trial for HER2+ BCBM with ZN-1041, capecitabine and trastuzumab combination therapy is planned. Clinical trial information: NCT04487236."

Clinical data • Preclinical • Breast Cancer • CNS Tumor • Hepatology • HER2 Breast Cancer • Oncology • Pain • Solid Tumor

The Oncology Institute Featured on Four Abstracts at ASCO 2023 Annual Meeting (GlobeNewswire) - "The Oncology Institute...is featured on four authored abstracts at the American Society of Clinical Oncology (ASCO) Annual Meeting being held at the McCormick Place Convention Center in Chicago, Illinois June 2-6, 2023."

P1/2 data • P3 data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor