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Datopotamab deruxtecan application in the EU for patients with advanced nonsquamous non-small cell lung cancer voluntarily withdrawn

On December 24, 2024 AstraZeneca and Daiichi Sankyo reported that they have voluntarily withdrawn the marketing authorisation application (MAA) in the EU for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) based on the TROPION-Lung01 Phase III trial (Press release, AstraZeneca, DEC 24, 2024, View Source [SID1234649266]).

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The decision to withdraw the MAA was informed by feedback from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA). AstraZeneca and Daiichi Sankyo will continue to work to bring datopotamab deruxtecan to patients with lung cancer in the EU who can benefit and are committed to unlocking the potential of this medicine in lung cancer through our robust clinical development programme which includes seven pivotal trials in various lung cancer settings.

AstraZeneca and Daiichi Sankyo’s application in the EU for datopotamab deruxtecan for the treatment of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer based on the TROPION-Breast01 Phase III trial remains under review.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 In Europe, nearly half a million lung cancer cases were diagnosed 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 While immunotherapy and targeted therapies have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive chemotherapy.3-5 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.3-5

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.6 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.7,8

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III 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 progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, and disease control rate 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 results from TROPION-Lung01, as presented at the European Society for Medical Oncology 2023 Congress, showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS over docetaxel. OS results were presented at the IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology in September 2024.

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 programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised 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.

Datopotamab deruxtecan has been granted Breakthrough Therapy Designation by the US Food and Drug Administration for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) NSCLC with disease progression on or after treatment with an EGFR-tyrosine kinase inhibitor and platinum-based chemotherapy. AstraZeneca and Daiichi Sankyo have submitted a Biologics License Application for datopotamab deruxtecan for this potential indication.

Datopotamab deruxtecan clinical development programme
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

CStone Pharmaceuticals’ blockbuster product CS2009 (a triple antibody against PD-1, VEGF, and CTLA-4) has submitted a clinical trial application in Australia

On December 2024 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing oncology drugs, reported that it has submitted a clinical trial application (CTA) in Australia for CS2009 (a trispecific antibody targeting PD-1, VEGF, and CTLA-4), its second-generation blockbuster product, for the treatment of various solid tumors (Press release, CStone Pharmaceauticals, DEC 23, 2024, View Source [SID1234656223]). The study has also been registered and publicly disclosed on Clinicaltrials.gov (registration number: NCT06741644).

CS2009 is a trispecific antibody with an innovative structural design that simultaneously targets PD-1, VEGFA, and CTLA-4. CS2009 possesses balanced anti-PD-1 and anti-CTLA-4 affinities , preferentially targeting and blocking PD-1 and CTLA-4 on double-positive tumor-infiltrating lymphocytes (TILs) while sparing CTLA-4 on single-positive cells. This approach minimizes potential systemic toxicity while maintaining efficacy. CS2009 also induces efficient internalization, reducing the expression of the immunosuppressive molecules PD-1 and CTLA-4 on the surface of double-positive TILs. Furthermore, CS2009 retains full anti-VEGF activity, and preclinical data demonstrates a significant synergistic effect between its anti-VEGF activity and immune checkpoint inhibitory activity —cross-linking with VEGFA significantly enhances anti-PD-1 and anti-CTLA4 activity.

CStone Pharmaceuticals presented preclinical data for CS2009 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These data demonstrate that CS2009 exhibits significantly superior anti-tumor activity compared to potential competitors, potentially targeting a broad range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, liver cancer, and gastric cancer, making it a first-in-class/best-in-class, next-generation immunotherapy backbone product.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said: "We are pleased to see the on-scheduled submission of the Phase I clinical trial application for CS2009. This marks another major milestone in CStone’s Pipeline 2.0. CS2009 is a novel trispecific antibody that we independently developed from molecular design, a project initiated in 2022. With extensive preclinical data supporting its potential as an alternative to existing PD-(L)1 therapies, CS2009 has smoothly entered clinical development. We will soon initiate its first-in-human study in Australia. We look forward to seeing CS2009’s potential benefit to cancer patients, particularly those with low PD-L1 expression or negative PD-L1 who have not responded well to PD-(L)1 therapies."

CStone Pharmaceuticals plans to initiate a global, multi-center, first-in-human study of CS2009 in Australia in early 2025, and will gradually expand to China and the United States in the future.

About CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody)

CS2009 is a trispecific molecule targeting PD-1, VEGFA, and CTLA-4. As a trispecific antibody targeting major tumor types, it holds first-in-class/best-in-class potential. CS2009 boasts a differentiated molecular design, combining three clinically validated targets. It can reactivate near-exhausted tumor-infiltrating T cells and exhibits VEGF neutralization activity comparable to that of existing anti-VEGF antibodies. It covers a wide range of disease indications, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer.

In November 2024, CStone Pharmaceuticals presented preclinical data for CS2009 at the 39th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. These data demonstrated that CS2009 exhibited significantly superior anti-tumor activity compared to potential competing products, including dual PD-1/CTLA-4 antibodies, dual PD-1/VEGF antibodies, and anti-PD-1/anti-CTLA-4 combination therapies.

AbelZeta to Attend 43rd Annual J.P. Morgan Healthcare Conference and Join Panel at 8th Annual BFC Healthcare Conference

On December 23, 2024 AbelZeta Pharma, Inc. ("AbelZeta" or the "Company"), a global clinical-stage biopharmaceutical company focused on the discovery and development of innovative and proprietary cell-based therapeutic products, will attend the 43rd Annual J.P. Morgan Healthcare Conference on January 13-16, 2025, in San Francisco, CA, and host meetings showcasing the Company’s recent accomplishments and sharing strategic plans moving forward (Press release, AbelZeta, DEC 23, 2024, View Source [SID1234649271]). The Company’s Chairman and CEO, Tony (Bizuo) Liu, has also been invited as a panel speaker at the 8th Annual BFC Global Healthcare BD and Investment Conference on Sunday, January 12, 2025.

Session: Faith to Incubate: Global Biotech Investment Trends and Focus
Time & Date: January 12, 2025, 09:15 – 10:15 PST
Location: The St. Regis San Francisco
Registration: View Source

U.S. Food and Drug Administration Accepts for Priority Review Nuvation Bio’s New Drug Application for Taletrectinib for the Treatment of Advanced ROS1-positive Non-Small Cell Lung Cancer

On December 23, 2024 Nuvation Bio Inc. (NYSE: NUVB), a global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported that the U.S. FDA has accepted the company’s NDA for taletrectinib, an investigational next-generation ROS1 tyrosine kinase inhibitor (TKI), for the treatment of advanced ROS1+ NSCLC (line agnostic) (Press release, Nuvation Bio, DEC 23, 2024, View Source [SID1234649268]). The U.S. FDA has granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 23, 2025. Priority Review designation underscores the significant advancement taletrectinib may offer patients with ROS1+ NSCLC, for which there remains a high unmet need for new treatment options. Taletrectinib previously received Orphan Drug Designation and is the only ROS1 TKI currently in development that has received Breakthrough Therapy Designation from the U.S. FDA for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs.

"We are thrilled to reach this important milestone for taletrectinib, a significant step forward for people living with ROS1-positive NSCLC who urgently need new treatment options," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "With data from over 300 patients—the largest ROS1-positive NSCLC dataset to date supporting an original NDA—taletrectinib has demonstrated the potential to deliver durable and meaningful benefits."

Dr. Hung continued, "Since acquiring AnHeart Therapeutics earlier this year, including taletrectinib, we have executed on our plan to advance taletrectinib toward a full U.S. regulatory approval. The FDA’s Priority Review reflects the strength of our clinical data and the promise taletrectinib holds for patients. As we prepare for a launch as early as mid-2025, we’re taking critical steps to establish Nuvation Bio as a commercial oncology organization, reinforcing our commitment to bringing innovative therapies to patients who need them most."

The NDA is based on the pooled results from the pivotal Phase 2 TRUST-I and TRUST-II studies of taletrectinib, which were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2024.

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+ NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1+ 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 Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC. Based on pooled results of the TRUST-I and TRUST-II clinical studies, the U.S. FDA has accepted for Priority Review Nuvation Bio’s NDA for taletrectinib for the treatment of patients with advanced ROS1+ NSCLC (line agnostic, full approval). Based on results of the TRUST-I clinical study, China’s NMPA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who have previously been treated with a ROS1 TKI and has accepted and granted Priority Review Designation to an NDA for patients who have not previously been treated with a ROS1 TKI.

Summary of the Pivotal Pooled TRUST-I and TRUST-II Data

The pooled efficacy and safety data from the TRUST-I and TRUST-II studies presented at ESMO (Free ESMO Whitepaper) are as of June 7, 2024; both studies remain ongoing. The ESMO (Free ESMO Whitepaper) data set includes 337 patients with advanced ROS1+ NSCLC who received 600mg of taletrectinib orally once daily in 21-day cycles.

The primary endpoint of these registrational studies is confirmed objective response rate (cORR) as assessed by an independent review committee (IRC). Key secondary endpoints include intracranial cORR, duration of response (DOR), progression-free survival (PFS), and safety.

The Nuvation Bio press release summarizing the pooled results can be viewed here.

About ROS1+ NSCLC

Each year, more than one million people globally are diagnosed with NSCLC, the most common form of lung cancer. It is estimated that approximately 2% of people with NSCLC have ROS1+ disease. Up to 35% of people newly diagnosed with metastatic ROS1+ NSCLC have tumors that spread to their brain, increasing up to 55% for those whose cancer has progressed following initial treatment. Despite recent progress for people with ROS1+ NSCLC, there remains a need for more effective and tolerable treatment options.

BridgeBio Oncology Therapeutics (BBOT) to Participate in the 43rd Annual J.P. Morgan Healthcare Conference 2025

On December 23, 2024 TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics ("BBOT" or the "Company"), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, reported that the company’s Chief Executive Officer, Eli Wallace, PhD, will provide a company overview at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025, at 9:30 a.m. PT, and will host one-on-one investor meetings in San Francisco, CA (Press release, BridgeBio, DEC 23, 2024, View Source [SID1234649267]).