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

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

Zion Pharma Announces Global Agreement with Roche to Develop and Commercialize a Blood Brain Barrier Penetrant Oral HER2 Tyrosine Kinase Inhibitor (Businesswire) - "Zion Pharma Limited...announced that Roche has acquired the global rights to Zion’s lead program, ZN-A-1041. ZN-A-1041 is an orally administered selective tyrosine kinase inhibitor targeting the Human Epidermal Growth Factor Receptor 2 (HER2). ZN-A-1041 was designed to be blood-brain-barrier-penetrant, and has the potential to treat or prevent the onset of brain metastases in patients with HER2-positive metastatic breast cancer. Up to 50% of patients with HER2-positive metastatic breast cancer will develop brain metastasis during the course of the disease....After a transition period, Roche will be responsible for the further development, manufacturing, and commercialization of ZN-A-1041 globally. Zion will receive up to $70 million USD in upfront and near-term milestone payments pending achievement of certain milestone events."

M&A • 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

New P1 trial • 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; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Zion Pharma Announces Initiation of Phase 1 Study (Businesswire) - "Zion...today announced the initiation of its Phase 1 study, in the United States, for its lead program ZN-A-1041...ZN-A-1041 is being developed to address the unmet medical need associated with brain metastases accompanying HER2+ advanced breast cancer...We recently completed a $20 million Series A follow-on that will provide us sufficient funding for the next two years...'With our recent financing, we expect to complete the ZN-A-1041 Phase 1 study in the U.S. and China and advance several of our other programs into IND-enabling studies.'"

Financing • Trial status • 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; Not yet recruiting; Sponsor: Suzhou Zanrong Pharma Limited

Clinical • Combination therapy • New P1 trial • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor