Fam-trastuzumab deruxtecan-NXKI

Data from Phase 1b/2 clinical trial to be presented at 2024 San Antonio Breast Cancer Symposium (SABCS) show encouraging clinical activity in patients with heavily pretreated HER2-positive breast cancer who had received multiple HER2-targeted agents, including fam-trastuzumab deruxtecan-nxki (ENHERTU®)Combination therapy was well tolerated with a manageable safety profile consistent with prior experience with each investigational agentData contribute to growing evidence supporting evorpacept activity in combination with anti-HER2-targeted agents among patients with HER2-positive cancers SOUTH SAN FRANCISCO, Calif., Dec. 10, 2024 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc. (“ALX Oncology” or “the Company”) (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, announced results from a Phase 1b/2 clinical trial demonstrating the company’s investigational CD47-blocker evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab generates promising anti-tumor activity in patients with both HER2-positive and HER2-low advanced breast cancer. The findings, which are the first from a clinical trial evaluating the safety and efficacy of evorpacept and zanidatamab in heavily pretreated patients with metastatic breast cancer (mBC), will be presented on Thursday, December 12 in a poster spotlight presentation (#PS8-09) at the 2024 San Antonio Breast Cancer Symposium (SABCS). “These data suggest that HER2-positive patients whose cancer has been heavily pretreated may benefit from CD47 inhibition via evorpacept’s unique mechanism when combined with a HER2-targeted agent,” said Alberto J. Montero, M.D., MBA, Clinical Director, Breast Cancer Medical Oncology Program, Case Western Reserve University, and the study’s principal investigator. “New therapeutic options with better safety profiles are desperately needed for these patients, and this is particularly true once disease progresses following advanced, standard-of-care therapies such as ENHERTU.” The Phase 1b/2 open-label, multi-center clinical trial (NCT05027139) evaluated the potential of evorpacept, a highly differentiated, investigational CD47 blocker, in combination with zanidatamab, a dual HER2-targeted bispecific antibody, as a novel treatment for patients with previously treated inoperable, locally advanced, or metastatic HER2-expressing breast cancer and other cancers. Part one of the trial evaluated the safety and recommended doses for the combination; part two assessed the anti-tumor activity of the resulting combination. The SABCS poster presentation will include efficacy findings from all three of the part-two trial cohorts: Cohort 1 (n=21) consisted of patients with HER2-positive breast cancer who had received a median of six prior systemic therapies in the metastatic setting. Notably, all patients in Cohort 1 had received prior fam-trastuzumab deruxtecan-nxki (ENHERTU®). Patients were enrolled based on local assessment of tumor samples or central assessment. Of the 21 patients enrolled in Cohort 1, nine were found to be HER2-positive based on central assessment. Cohort 2 (n=15) consisted of patients with HER2-low breast cancer who had received a median of five prior systemic therapies. Cohort 3 (n=8) consisted of patients with other HER2-expressing cancers. Key trial results to be shared at SABCS 2024 include: HER2-positive by central assessment mBC: Patients in Cohort 1 who were HER2-positive by central assessment (n=9) showed the greatest anti-tumor activity with a confirmed objective response rate (cORR) of 55.6% and a median progression free survival (mPFS) of 7.4 months.HER2-positive mBC: Overall, patients in Cohort 1 (n=21) had a confirmed cORR and mPFS of 33.3% and 3.6 months, respectively.HER2-low mBC: Responses were also observed in Cohort 2 (cORR: 20.0%; mPFS: 1.9 months).As of the August 2024 data cutoff, median follow-up was 9.6 months, with six patients still on treatment. The median duration of response was not reached for Cohort 1 patients (range: 3.6-25.9 months) and was 5.5 months for Cohort 2 patients (range: 3.6-11.0 months), with responses ongoing, including the longest observed response, in each cohort. Most treatment-related adverse events were grade 1 or 2. The most frequent adverse events due to any cause were fatigue, nausea, diarrhea, and infusion-related reactions. There were no treatment-related deaths in the study and no non-infectious pulmonary toxicities. These safety findings are consistent with those observed in the >700 patients treated with evorpacept to date. “This study adds to the growing body of evidence suggesting that evorpacept can treat HER2-positive cancers after patients progress on multiple conventional HER2-directed therapies, given that the encouraging response rate of 55 percent in this population would not be expected,” said Jason Lettmann, Chief Executive Officer at ALX Oncology. “The data that will be presented this week also further validate our biomarker strategy, showing that confirmed HER2-expression drove the largest benefit for patients. Collectively, these findings provide us with the proof of concept necessary to accelerate our clinical plans to advance evorpacept in HER2-positive breast cancer.” A copy of the poster presentation will be available on the Publications section of ALX Oncology’s website at the start of the presentation at SABCS on December 12, 2024. About ALX Oncology ALX Oncology (Nasdaq: ALXO) is a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives. ALX Oncology’s lead therapeutic candidate, evorpacept, has demonstrated potential to serve as a cornerstone therapy upon which the future of immuno-oncology can be built. Evorpacept is currently being evaluated across multiple ongoing clinical trials in a wide range of cancer indications. More information is available at www.alxoncology.com and on LinkedIn @ALX Oncology. Cautionary note regarding forward-looking statements This press release contains forward-looking statements that involve substantial risks and uncertainties. Forward-looking statements include statements regarding future results of operations and financial position, business strategy, product candidates, planned preclinical studies and clinical trials, results of clinical trials, research and development costs, regulatory approvals, timing and likelihood of success, plans and objects of management for future operations, as well as statements regarding industry trends. Such forward-looking statements are based on ALX Oncology’s beliefs and assumptions and on information currently available to it on the date of this press release. Forward-looking statements may involve known and unknown risks, uncertainties and other factors that may cause ALX Oncology’s actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. These and other risks are described more fully in ALX Oncology’s filings with the Securities and Exchange Commission (SEC), including ALX Oncology’s Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and other documents ALX Oncology files with the SEC from time to time. Except to the extent required by law, ALX Oncology undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

TOKYO & BASKING RIDGE, N.J.--( BUSINESS WIRE )--Datopotamab deruxtecan (Dato-DXd) has been granted Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR-mutated) non-small cell lung cancer (NSCLC) with disease progression on or after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). The U.S. Food and Drug Administration (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat serious conditions and address significant unmet medical needs. The medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines. The FDA granted this BTD based on data from the TROPION-Lung05 phase 2 trial with supporting data from the TROPION-Lung01 phase 3 trial. Results from a pooled analysis of patients with previously treated EGFR-mutated NSCLC in these studies were presented this month at the European Society of Medical Oncology (ESMO) Asia 2024 Congress. This is the first BTD for datopotamab deruxtecan and the twelfth BTD across Daiichi Sankyo’s oncology pipeline. “ The Breakthrough Therapy Designation granted by the FDA underscores the significant unmet need for new treatments for patients with previously treated EGFR-mutated non-small cell lung cancer who have experienced disease progression,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “ Datopotamab deruxtecan has the potential to play an important role in improving outcomes and we look forward to working closely with the FDA to bring this medicine to patients as quickly as possible.” “ This Breakthrough Therapy Designation reinforces datopotamab deruxtecan as a promising potential therapy for patients with EGFR-mutated lung cancer who continue to face significant unmet needs following disease progression on or after initial treatments,” said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. “ We are proud to have long supported patients with EGFR-mutated lung cancer and look forward to the possibility of bringing another innovative treatment option to this community.” Daiichi Sankyo and AstraZeneca recently announced the submission of a new Biologics License Application for accelerated approval in the U.S. for datopotamab deruxtecan for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior systemic therapies, including an EGFR-directed therapy. About TROPION-Lung05 TROPION-Lung05 is a global, multicenter, single-arm, open-label phase 2 trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one TKI (with or without other systemic therapies) and on or after one regimen of platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumors with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial. The primary trial endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety. TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information visit ClinicalTrials.gov . About TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety. TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology in September 2024. About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 Lung cancer is broadly split into small or non-small cell lung cancer, the latter accounting for about 80% of cases. 2 Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation. 3,4 The majority of EGFR mutations occur in tumors of nonsquamous histology. 5 For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting is an EGFR TKI. 6 While EGFR TKIs have improved outcomes in the first-line setting, most patients eventually experience disease progression and receive subsequent therapies, such as chemotherapy. 7,8,9,10 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 11 There is currently no TROP2 directed ADC approved for the treatment of lung cancer. 6,12 About Datopotamab Deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 low or negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan. About the DXd ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . _______________________________ References 1 World Health Organization. Global Cancer Observatory: Lung. Accessed December 2024. 2 American Cancer Society. Key Statistics for Lung Cancer . Accessed December 2024. 3 Szumera-Ciećkiewicz A, et al. Int J Clin Exp Pathol . 2013;6(12): 2800-2812. 4 Ellison G, et al. J Clin Pathol . 2013;66(2):79-89. 5 Prabhakar C. Translational Lung Cancer Research . 2015; 4(2), 110-118. 6 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed December 2024. 7 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 8 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 9 Morgillo F, et al. ESMO Open . 2016;1:e000060. 10 Han B, et al. Onco Targets Ther . 2018;11:2121-9. 11 Mito R, et al. Pathol Int . 2020;70(5):287-294. 12 Rodríguez-Abreau D, et al. Ann Onc . 2021 Jul;32(7): 881-895.