On June 1, 2024 Accutar Biotechnology, Inc., a biotechnology company focusing on artificial intelligence (AI)-enabled drug discovery, reported data from an ongoing Phase 1 study of AC699 monotherapy in patients with ER-positive / HER2-negative locally advanced or metastatic breast cancer (Press release, Accutar Biotechnology, JUN 1, 2024, View Source;Breast-Cancer-at-ASCO-2024 [SID1234643969]). The data will be presented in a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL on June 1, 2024.

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AC699 is a potent and selective orally bioavailable, chimeric degrader of estrogen receptor (ER) α, and offers a potential new breast cancer treatment option based on a differentiated mechanism of action as compared to fulvestrant and novel SERDs with deeper ERα degradation as demonstrated in preclinical studies. AC699 is currently being evaluated in an ongoing Phase 1 clinical study as a single agent for the treatment of ER-positive / HER2-negative locally advanced or metastatic breast cancer (NCT05654532). The primary objectives are to evaluate the safety and tolerability of AC699. Secondary and exploratory objectives include pharmacokinetics, preliminary efficacy and pharmacodynamic evaluation. The study uses a 3+3 dose-escalation design, with once-daily oral dosing of AC699 at 100, 200, 300, 400, and 600 mg.

Phase 1 Study Results:

As of April 8, 2024, 29 participants were enrolled and treated with AC699 at doses ranging from 100-400 mg. The participants had a median of 5 (range 2-10) prior lines of therapy, including 3 (range 1-8) prior lines in the metastatic setting
The objective response rate was 21% (4/19) and increased to 50% (4/8) for those who had an ESR1 mutation
There were no > Grade 3 drug-related adverse events (AEs), no dose limiting toxicities, no discontinuations and no dose reductions due to AEs
AEs related to AC699 occurred in 38% of participants and included nausea (14%), hot flush (14%), and fatigue (10%)
The maximum tolerated dose had not been reached yet
Details of the poster presentation at ASCO (Free ASCO Whitepaper) 2024 are as follows:

Date/Time: June 1, 2024, 9:00 AM – 12:00 PM CDT
Abstract Number: 3074
Title: Preliminary results from a phase 1 study of AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer.
Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Abstracts and full session details can be accessed through the ASCO (Free ASCO Whitepaper) meeting planner: Link
"We are extremely pleased with the groundbreaking safety and efficacy that AC699 has demonstrated thus far in Phase 1, with early evidence of its best-in-class potential, especially for patients with ESR1 mutations," said Jie Fan, Ph.D., Chief Executive Officer of Accutar Biotechnology, Inc. "We look forward to completing the dose escalation portion of the study and starting the Phase 2 study soon. We believe that the oral dosing of AC699 and its differentiated mechanism of action, as compared to fulvestrant and novel SERDs, can potentially provide a new safe and effective treatment option for this patient population."

About AC699 and the Phase 1 Study (AC699-001)

AC699 is an investigational orally bioavailable, chimeric degrader of estrogen receptor (ER) α. In preclinical studies, AC699 has demonstrated potent and selective protein degradation of ERα wildtype and mutants with favorable pharmacological properties, as well as promising anti-tumor activities in ER-positive animal tumor models.

The purpose of the Phase 1 multi-center, open-label study is to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AC699 treatment in patients with ER-positive / HER2-negative locally advanced or metastatic breast cancer (NCT05654532). Additional information on this clinical trial can be found on www.clinicaltrials.gov.

On June 1, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported that results from the pivotal Phase 2 TRUST-I study conducted in China evaluating taletrectinib, its investigational next-generation ROS1 tyrosine kinase inhibitor (TKI), were published today in the Journal of Clinical Oncology (JCO) and will be highlighted in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place in Chicago, Illinois (Press release, Nuvation Bio, JUN 1, 2024, View Source [SID1234643968]).

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Data were reported from 173 patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) who were treated with taletrectinib. Results showed tumors shrank (confirmed objective response rate, cORR, as assessed by an independent review committee, IRC) in 91% of taletrectinib-treated patients who had not previously been treated with a ROS1 TKI (ROS1 TKI-naïve) and 52% of taletrectinib-treated patients who had previously been treated with crizotinib (ROS1 TKI-pretreated). Taletrectinib continued to show robust activity in patients with disease that spread to the brain, as well as in patients with acquired resistance mutations, including G2032R.

After median follow-up of 23.5 months in TKI-naïve patients, median duration of response (IRC-assessed) and median progression-free survival (IRC-assessed) were not reached. After median follow-up of 9.7 months in TKI-pretreated patients, median duration of response and median progression-free survival were 10.6 months and 7.6 months, respectively. Taletrectinib’s safety profile was consistent with previous reports, with a low incidence of neurologic treatment-emergent adverse events (TEAEs).

"Current treatments for advanced ROS1-positive NSCLC have significant limitations, and people living with this disease remain in need of new options that are both well tolerated and offer durable responses," said Caicun Zhou, M.D., Ph.D., Principal Investigator of the TRUST-I study and Professor and Director of the Department of Oncology at Shanghai East Hospital, Tongji University. "These TRUST-I results reinforce taletrectinib’s strong efficacy signal and favorable safety profile, underscoring its potential to become a new treatment option for patients."

"TRUST-I is one of the largest prospective trials conducted to date in ROS1-positive NSCLC. We now have data with long-term follow-up and are very pleased that results remain highly consistent with previously reported taletrectinib data, demonstrating its best-in-class potential," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We look forward to further advancing taletrectinib and plan to share results from the global, pivotal TRUST-II study by the end of 2024, as we aim to become a commercial-stage organization by the end of 2025."

Phase 2 TRUST-I Study Results

TRUST-I (NCT04395677) is a pivotal Phase 2, multicenter, single-arm, open-label study evaluating taletrectinib as a monotherapy in 173 patients with advanced ROS1-positive NSCLC in China who had either not previously been treated with a ROS1 TKI (TKI-naïve) or had previously been treated with crizotinib (TKI-pretreated). Almost all patients received 600 mg of taletrectinib orally once-a-day in 21-day treatment cycles. 21% of TKI-naïve patients and 34% of TKI-pretreated patients had received prior chemotherapy. The primary endpoint of this registrational study was cORR as assessed by IRC, and key secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety.

As of November 29, 2023, results from TRUST-I as assessed by an IRC showed:

In TKI-naïve patients (n=106):

90.6% of patients’ tumors shrank following treatment with taletrectinib (cORR).
Brain tumors shrank in 87.5% of taletrectinib-treated patients who had measurable central nervous system tumors (n=8; intracranial cORR).
After median follow-up of 23.5 months, median duration of response and median progression-free survival were not reached.
At two years, 78.6% of patients who responded following treatment with taletrectinib were still responding, and 70.5% of patients were still progression-free.
In TKI-pretreated patients (n=66):

51.5% of patients’ tumors shrank following treatment with taletrectinib (cORR).
Brain tumors shrank in 73.3% of taletrectinib-treated patients who had measurable central nervous system tumors (n=15; intracranial cORR).
Tumors shrank in 66.7% of taletrectinib-treated patients with G2032R mutations (n=12).
After median follow-up of 9.7 months, median duration of response was 10.6 months and median progression-free survival was 7.6 months.
At nine months, 69.8% of patients who responded following treatment with taletrectinib were still responding, and 47.4% were still progression-free.
Taletrectinib’s safety profile was consistent with previous reports. The most frequent TEAEs were increased liver enzymes (increased aspartate aminotransferase: 76%; increased alanine aminotransferase: 68%); diarrhea (70%); vomiting (53%), and anemia (49%), most of which were grade 1 or 2. Incidence of neurologic TEAEs were low; the most common was dizziness (23%), most of which was grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.

The JCO publication, "Efficacy and Safety of Taletrectinib in Chinese Patients with ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study," is available at View Source

The corresponding oral presentation, "Efficacy and Safety of Taletrectinib in Patients with Advanced or Metastatic ROS1+ Non-Small Cell Lung Cancer: The Phase 2 TRUST-I Study," (Abstract #8520) will be delivered by Wei Li, M.D., a TRUST-I investigator and Professor at the Department of Medical Oncology at Shanghai East Hospital, Tongji University, at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting in the "Lung Cancer – Non-Small Cell Metastatic" session occurring today, Saturday, June 1, 2024, at 4:30-6:00 p.m. CT/5:30-7:00 p.m. ET, and will be made available on Nuvation Bio’s website at www.nuvationbio.com/publications.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1-positive NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors (TKIs).

In 2021, AnHeart Therapeutics Ltd., a Nuvation Bio company, entered into an exclusive license agreement with Innovent Biologics, Inc. for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau, and Taiwan.

About ROS1-positive NSCLC

More than one million people globally are diagnosed with NSCLC annually, the most common form of lung cancer. It is estimated that approximately 1-3% of people with NSCLC are ROS1-positive. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment. While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC who remain in need of new options.

On June 1, 2024 Ankyra Therapeutics, a clinical-stage oncology company developing anchored immunotherapies to improve the therapeutic window for immuno-oncology drugs, reported that it is presenting a Trial in Progress poster for the phase 1 ANCHOR clinical trial at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 31 – June 4, 2024 in Chicago, IL (Press release, Ankyra Therapeutics, JUN 1, 2024, https://www.businesswire.com/news/home/20240601270271/en/Ankyra-Therapeutics-Announces-Trial-in-Progress-Poster-Presentation-at-2024-ASCO-Meeting-and-Approval-of-ANK-101-Phase-1-Protocol-Amendment [SID1234643967]).

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Ankyra Therapeutics has developed an anchored drug-delivery platform based on linking immunotherapy drugs to aluminum hydroxide. The linked compounds are delivered locally to the tumor, where they are retained for several weeks promoting anti-tumor activity without systemic toxicity. Ankyra’s lead asset, ANK-101, is comprised of interleukin-12 with an alum-binding peptide that enables direct linkage with aluminum hydroxide. The ANCHOR study is a multi-institution, first-in-human, phase I clinical trial of ANK-101 in patients with superficially accessible solid tumors who have progressed after standard therapy was initiated in February 2024. The primary objectives of the study are to determine the safety, tolerability, and recommended dose of ANK-101 for further studies. The trial is active at five clinical study sites: Massachusetts General Hospital in Boston, MA; Providence Cancer Institute in Portland, OR; University of Pittsburgh in Pittsburgh, PA; Princess Margaret Hospital in Toronto, ON; and the National Cancer Institute (NCI), part of the National Institutes of Health, in Bethesda, MD. The poster presentation will include the rationale for the trial, study objectives, clinical trial design, and an update on accrual. The study will also evaluate pharmacokinetics, immune biomarkers, and quality of life.

In addition, Ankyra has received clearance from both the U.S. Food and Drug Administration (FDA) and Health Canada to amend the phase I clinical trial to include a second dose-escalation and expansion part to evaluate ANK-101 for injection into solid tumors located in visceral organs. This part will run concurrently with the current Phase I study with dosing to begin once patients in the superficial part have cleared a 21-day dose-limiting toxicity (DLT) observation period.

"We are delighted with the progress in the current phase I study which will help establish the initial safety profile and dosing selection for ANK-101," stated Howard L. Kaufman, MD, CEO of Ankyra Therapeutics. Dr. Kaufman also stated that "this study is the first step to realize the potential for anchored immunotherapy to deliver high doses of immunotherapy without systemic toxicity, which could represent an important advance in how we deliver effective cancer treatment in a safer manner." Joe Elassal, MD, Chief Medical Officer at Ankyra added "the recent approval to extend ANK-101 to visceral tumors is especially exciting as we can now study a broader patient population that could extend the potential indications for ANK-101 treatment".

For patients interested in enrolling in this clinical trial at NCI, please call NCI’s toll-free number: 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615); visit the website: View Source; and/or email: [email protected].

Title: A phase 1, open-label, dose escalation study on the safety and tolerability of ANK-101 in advanced solid tumors
Session Type: Poster Session
Session Title: Developmental Therapeutics – Immunotherapy
Track: Developmental Therapeutics – Immunotherapy
Sub Track: New Targets and New Technologies (IO)
Session Date and Time: Saturday June 1, 2024 9:00 AM CDT
Location: Hall A
Poster Board Number: 158a
Published Abstract Number: TPS2689
Citation: J Clin Oncol. 42, 2024 (suppl 16; abstr TPS2689)

The poster will be available on the publications section of Ankyra’s website after the meeting at View Source

About ANK-101

ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The Phase 1 first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts.

On June 1, 2024 Tempus, a leader in artificial intelligence and precision medicine, reported an expansion of its collaboration with AstraZeneca, which leverages Tempus Next to arm physicians with technology that supports the delivery of guideline-directed biomarker testing for patients with non-small cell lung cancer (NSCLC) (Press release, Tempus, JUN 1, 2024, View Source [SID1234643966]). The magnitude and frequency of updates to oncology guidelines each year make it difficult for the updates to be rapidly incorporated into patient treatment plans. As part of a larger, strategic collaboration, the two companies are now expanding upon a pilot program that utilizes Next, Tempus’ care pathway intelligence platform, to help physicians determine if their patients with NSCLC may benefit from guideline-directed molecular testing, including testing for epidermal growth factor receptor (EGFR) mutations.

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EGFR is a biomarker that presents in some patients with NSCLC and that has specific targeted therapies associated with it. Currently, ~30-40% of eligible NSCLC patients do not receive appropriate testing1. In September 2023, Tempus and AstraZeneca initiated a pilot program to leverage Next to identify this specific care gap at participating provider sites, using AI to scan unstructured clinical data to understand which patients may be eligible for testing based on clinical guidelines, and notifying treating physicians to inform care. The pilot’s initial success within the first six months prompted a new expansion of the program to support deployment of the care pathway model in a total of 15 provider sites.

"Next was designed to ensure all patients have access to treatment plans based on the most up-to-date guidelines by equipping physicians with cutting-edge tools in their existing workflows to support the delivery of evidence-based care," said Chris Scotto DiVetta, Senior Vice President, AI Applications at Tempus. "We were excited to see initial success in this program and look forward to contributing to a future where advanced technology and medical expertise unite to improve outcomes for all patients."

Tempus Next is designed to accelerate the adoption of precision medicine and enhance patient outcomes. The solution integrates seamlessly with EMRs in order to analyze a comprehensive suite of data—including clinical notes, molecular information, and imaging—to pinpoint certain deviations from care guidelines. Participating health systems receive regular updates, supporting guideline-directed care for their patients. To learn more, visit tempus.com/oncology/care-pathway-solution.

On June 1, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported long-term follow-up results, including the first-ever overall survival (OS) findings, from the Phase 2b HERIZON-BTC-01 clinical trial of zanidatamab in previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) (Press release, Jazz Pharmaceuticals, JUN 1, 2024, View Source [SID1234643956]). These data will be featured at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a poster presentation during the Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary session on June 1, 2024, at 1:30-4:30 p.m. CDT. Zanidatamab is a human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody being studied in multiple solid tumors.

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For the trial’s primary endpoint, results demonstrated that a confirmed objective response rate (cORR) by independent central review (ICR) was maintained at 41.3% (95% confidence interval (CI): 30.4, 52.8) and one additional patient achieved a complete response (n=2; 2.5%) since initial findings were presented at the ASCO (Free ASCO Whitepaper) Annual Meeting in 2023. The median duration of response (DoR), one of the trial’s key secondary endpoints, increased by approximately 2 months to 14.9 months (95% CI: 7.4, not reached), compared to the previously reported findings. In this data cut, zanidatamab demonstrated a median estimated OS, another secondary endpoint, of 15.5 months (95% CI: 10.4, 18.5) in all patients with HER2+ BTC, 18.1 months (95% CI:12.2, 23.2) in patients with IHC 3+ tumors, and 5.2 months (95% CI: 3.1, 10.2) in patients with IHC 2+ tumors. Results highlight the clinically meaningful benefits of sustained and durable responses with continued treatment with zanidatamab.

"Patients with BTC are typically diagnosed when their disease is at an advanced stage, which is associated with a poor prognosis," said Shubham Pant, M.D., M.B.B.S. professor in the Department of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "Historically, overall survival with standard-of-care chemotherapy in second-line patients with advanced BTC is reported to be between 6-9 months1 so there is a significant unmet need for targeted therapies that can potentially improve survival. The deep and durable responses seen in this study signal the potential to fill a critical unmet patient need with zanidatamab, a chemotherapy-free option, among patients with HER2-expressing cancers."

"We are encouraged by the updated results from the pivotal HERIZON-BTC-01 trial demonstrating sustained clinical activity in previously treated patients with advanced HER2-positive BTC. Results from HERIZON-BTC-01 were included in the Biologics License Application (BLA) for zanidatamab, which was granted Priority Review by the FDA earlier this week, as well as in the Marketing Authorization Application for zanidatamab which was recently submitted to the European Medicines Agency," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Clinical development of zanidatamab for the treatment of advanced HER2-positive BTC continues with HERIZON-BTC-302 (NCT06282575), the ongoing, global, randomized Phase 3 trial of zanidatamab in combination with standard-of-care therapy in the first-line setting for patients with HER2-positive BTC. We also look forward to investigating zanidatamab’s potential in other HER2-expressing solid tumors, including in cases resistant to prior HER2-targeted therapies."

Trial Results

Results from this long-term analysis of the Phase 2b HERIZON-BTC-01 trial (NCT04466891) indicate that zanidatamab monotherapy demonstrated sustained and durable antitumor responses in previously treated patients with HER2-positive unresectable, locally advanced, or metastatic BTC and support the clinically meaningful benefit of continued treatment with zanidatamab. The safety profile in all enrolled patients remained manageable with favorable tolerability compared with the initial analysis. Two (2.3%) patients discontinued treatment due to treatment-related adverse events (TRAEs).

The trial evaluated zanidatamab (20 mg/kg IV once every 2 weeks) in patients with HER2-positive, locally advanced unresectable, or metastatic BTC who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. All patients were required to have centrally confirmed HER2-amplified tumors (assessed by in situ hybridization). Patients (n=87) were assigned into two cohorts based on tumor IHC status: Cohort 1 (n=80) included patients who were IHC 2+/3+ (HER2-positive) and Cohort 2 (n=7) included patients who were IHC 0/1+. The median duration of follow-up was 21.9 (16-34) months. Tumors were assessed every 8 weeks per RECIST v1.1. Updated efficacy analyses include only Cohort 1, while safety analyses include Cohorts 1 and 2.

As of July 28, 2023, data from HER2-positive BTC patients enrolled in Cohort 1 (n=80) demonstrated:

With longer follow-up, the cORR was maintained from the initial analysis (n=33; 41.3%) (95% CI: 30.4, 52.8), with one additional complete response (n=2; 2.5%).
Although the trial was not designed to detect treatment effects by HER2 status, as previously reported, in a pre-planned subgroup analysis of cORR by HER2 expression, responses were observed in patients with IHC 3+ tumors (cORR: 51.6% [95% CI: 38.6%-64.5%]) and IHC 2+ tumors (cORR: 5.6% [95% CI: 0.1-27.3%])2.
A two-month increase in the median DoR to 14.9 months (95% CI: 7.4, not reached).
In patients with IHC3+ tumors, the median DoR was 14.9 months (95% CI: 7.4, not reached).
The DOR in the 1 responder with IHC 2+ tumors was 7.5 months.
A median OS (95% CI) of 15.5 months (95% CI: 10.4, 18.5).
The median OS in patients with IHC 3+ was 18.1 months (95% CI: 12.2, 23.2).
The median OS in patients with IHC 2+ was 5.2 months (95% CI: 3.1, 10.2).
Median progression-free survival (PFS) was maintained (5.5 months [95% CI: 3.6, 7.3]) compared with the initial analysis, which had a data cutoff of October 10, 2022.
In patients with IHC 3+ tumors, the median PFS was 7.2 months (95% CI: 5.4, 9.4) months.
In patients with IHC 2+ tumors, the median PFS was 1.7 months (95% CI: 1.0, 3.3) months.
As previously reported for Cohorts 1 and 2, zanidatamab demonstrated a manageable and tolerable safety profile, with no new safety signals identified and no deaths that were treatment related. TRAEs leading to dose reductions remained infrequent. Serious TRAEs occurred in eight (9.2%) patients. One patient experienced serious TRAEs since the initial analysis (alanine aminotransferase increased and aspartate aminotransferase increased).Treatment discontinuation rate was 2.3% and no additional patients discontinued treatment due to TRAEs since the initial analysis.

About BTC
BTC, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers globally and are often associated with a poor prognosis.3,4 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.5,6,7,8

About Zanidatamab
Zanidatamab is an investigational HER2-targeted bispecific antibody that can simultaneously bind two non-overlapping epitopes of the HER2 receptor, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.