Large cell neuroendocrine carcinoma of lung

RIDGEFIELD, Conn., Aug. 27, 2024 /PRNewswire/ -- Data from the Phase Ib Beamion LUNG-1 trial selected for late-breaking oral presentation in the Presidential Symposium at WCLC on Monday, September 9. The U.S. FDA and China's CDE have granted zongertinib Breakthrough Therapy Designation for patients with HER2-mutated NSCLC and who have received prior systemic therapy. Phase I trial data of a novel DLL3-targeting T-Cell Engager, which has already secured FDA Fast Track as well as FDA and EMA Orphan Drug Designations, will also be presented. At the IASLC 2024 World Conference on Lung Cancer (WCLC) Boehringer Ingelheim will present encouraging data from across its oncology pipeline, illustrating its aspiration to transform the lives of people with cancer by delivering meaningful advances. Carinne Brouillon, Head of Human Pharma at Boehringer said: "Every year, about 40,000 people worldwide are diagnosed with non-small cell lung cancer (NSCLC) with a HER2 mutation.i While targeted therapy is available for some cancers driven by HER2, people living with HER2-mutated NSCLC have few options. We are proud to be sharing new data evaluating our investigational zongertinib in this hard-to-treat setting. Our strong oncology pipeline underscores our strategic approach in advancing novel targeted treatments and cancer cell-directed therapies that have a potential to transform lives for generations of patients." Late-breaking results from the Beamion LUNG-1 trial, which is a Phase Ia/b trial evaluating the safety and efficacy of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor (TKI), will be presented at WCLC. This includes new data from a primary analysis of the first Cohort of Phase Ib in pre-treated patients with HER2m+ NSCLC to be presented in a Presidential Symposium on Monday, September 9, from 8:30AM - 10:00AM PDT (Location: Plenary Hall) and featured in the official WCLC Press Program. Highlighting the potential of zongertinib, the investigational oral therapy was recently granted Breakthrough Therapy Designation by the U.S. FDA and China's CDE for the treatment of adult patients with advanced, unresectable or metastatic NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. Investigating the potential of DLL3 targeted immunotherapy to transform the treatment of neuroendocrine carcinomas Exploring the promise of DLL3-targeted immunotherapy in transforming the treatment of neuroendocrine carcinomas, Boehringer will present data from the Phase I trial of its novel DLL3-targeting T-Cell Engager, BI 764532 in an Oral Presentation on Monday, September 9, from 2:22 PM-2:32 PM PDT (Location: 20A). This investigational treatment, which has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations, is currently being evaluated in patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) and extrapulmonary neuroendocrine cancer (epNEC). BI 764532 is designed to redirect T-cells to target tumors that express the DLL3 protein. In addition to the five abstracts to be presented at WCLC, Boehringer will also host a symposium titled "Emerging Therapies in Clinical Practice: What are the Patient Perspectives on the Future of Lung Cancer Treatment?" on Saturday, September 7, from 3:45PM to 4:45PM PDT (Location: 30DE). At Boehringer, cancer care is personal, which is why this event will explore patient viewpoints and expectations regarding the evolving landscape of lung cancer therapy. Data from Boehringer's oncology pipeline to be presented at WCLC: About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.ii NSCLC is the most common type of lung cancer.iii The condition is often diagnosed at a late stage,iv and fewer than 3 in 10 patients are alive five years after diagnosis.v People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Around 4.7% of lung cancers are driven by HER2 mutations (or gene alterations).i,vi About zongertinib Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is highly selective and being developed as a potential treatment for non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. HER2 is a member of the ErbB family of receptor tyrosine kinases (enzymes that act like chemical messengers). Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread. Read more here. About BI 764532 BI 764532 is an investigational DLL3/CD3 IgG-like T-Cell Engager under development as a potential new targeted immunotherapy for patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) & extrapulmonary neuroendocrine cancer (epNEC). The therapy is designed to directly redirect T-cells, potentially resulting in the selective killing of tumor cells by the body's own immune system. Pre-clinical in-vivo data suggests administration of DLL3/CD3 bispecific T-cell engager (ITE) monotherapy induces T-cell infiltration into tumor tissues, transforming a non-inflamed (cold) tumor microenvironment into an inflamed (hot) state. This process triggers tumor cell apoptosis, resulting in significant tumor regression. BI 764532 has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations. Read more here. About brigimadlin Brigimadlin (also known as BI 907828) is an investigational oral MDM2-p53 antagonist being developed as a potential treatment for certain types of cancer. The small molecule compound may inhibit the interaction between MDM2 and p53, restoring p53 wild type function. Inactivation of the tumor suppressor protein p53 is a central mechanism by which cancer cells drive tumor growth. Increased levels of the protein MDM2, a key negative regulator of p53, is a well-characterized inactivation mechanism, seen in about 5-7% of all cancer cases. About Boehringer Ingelheim in Oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim's generational commitment to driving scientific innovation is reflected by the company's robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer's ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Read more here. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Lean more at boehringer-ingelheim.com/us. i Chia, P. et al. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clinical Epidemiology. . ii International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: (Accessed August 2024). iii Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. iv Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 v National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). (Accessed: August 2024). vi Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012). MPR-US-103284 8/24 SOURCE Boehringer Ingelheim

Phanes’ PT217 is a delta-like ligand 3 (DLL3) and a cluster of differentiation 47 (CD47- targeting bispecific antibody. Image Credit: Huen Structure Bio / Shutterstock. The US Food and Drug Administration (FDA) has granted an orphan drug designation to Phanes Therapeutics’ PT217 in neuroendocrine carcinoma (NEC) indication. This is the second orphan drug designation the therapy has received from the FDA. In 2022, PT217 received the designation for the treatment of small cell lung cancer (SCLC). The orphan drug status gives sponsors tax credits from clinical trials, exemption from user fees, and a potential seven years of market exclusivity for the therapy after approval, compared to the usual five years. PT217 is a delta-like ligand 3 (DLL3) and a cluster of differentiation 47 (CD47)-targeting bispecific antibody. Phanes is investigating the therapy in patients with advanced or refractory cancers expressing DLL3, including SCLC, extrapulmonary NECs, and large cell neuroendocrine carcinoma of the lung (LCNEC). The Phase I SKYBRIDGE trial (NCT05652686) is evaluating the safety, tolerability and pharmacokinetics of PT217 in combination with Roche’s PD-L1 therapy Tecentriq (atezolizumab). Multiple pharmaceutical companies have invested in the development of bispecific antibody therapies . Earlier this month, Merck & Co (MSD) unveiled plans to acquire a CD3 and CD19-targeting T cell engager bispecific antibody, CN201, from Curon Biopharmaceutical. The deal is worth approximately $1.3bn in upfront and milestone-based payments. It is expected to close in Q3 this year. In May, Johnson & Johnson (J&J) paid $1.25bn to acquire global rights for Numab Therapeutics’ IL-4R and IL-31-targeting bispecific antibody. The therapy is being evaluated as a treatment for atopic dermatitis in a Phase I trial (NCT05859724). See Also: AstraZeneca wins approval for Imfinzi in NSCLC perioperative setting Hoth and Aronnax partner for HT-KIT cancer therapy development Other therapies in Phanes’s pipeline are a CD73-targeting monoclonal antibody PT199, a Claudin 18.2 (CLDN18.2), and the CD47-targeting bispecific antibody PT886. The company is evaluating PT199 as a combination treatment with BeiGene’s Tivimbra (tislelizumab) for solid tumours in a Phase I MORNINGSTAR trial (NCT05431270). The bispecific antibody PT886 is being trailed in combination with MSD’s Keytruda (pembrolizumab) in a Phase I/II TWINPEAK study (NCT05482893). The trial is expected to enrol approximately 114 participants with either unresectable or metastatic gastric adenocarcinoma, gastroesophageal junction (GEJ) adenocarcinoma, and pancreatic ductal adenocarcinoma (PDAC).

First Precision Radiopharmaceutical Therapy Targeting DLL3 Being Advanced for the Treatment of Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Abdera Therapeutics Inc., a biopharmaceutical company leveraging its advanced antibody engineering ROVEr™ platform to design and develop tunable, precision radiopharmaceuticals for cancer, today announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for ABD-147, the first delta-like ligand 3 (DLL3) targeting radiopharmaceutical for the treatment of small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Abdera plans to initiate a Phase 1 clinical trial in the second half of 2024. ABD-147 is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing DLL3. DLL3 is a protein found on the surface of neuroendocrine tumors, but rarely expressed on the surface of normal cells or tissues. “ABD-147 represents a potential best-in-class treatment for SCLC and other aggressive neuroendocrine tumors,” said Philippe Bishop, M.D., chief medical officer. “Leveraging our ROVEr platform, we custom-engineered ABD-147 with optimized pharmacokinetic properties and tumor penetration to destroy tumor cells while limiting radiation toxicity to the body. We are hopeful this highly potent next generation radiotherapeutic will provide a potential breakthrough addressing a critical medical need for the treatment of SCLC and other high-grade neuroendocrine cancers. We look forward to initiating a Phase 1 clinical trial of ABD-147 later this year.” The Phase 1, first-in-human, open-label clinical study aims to evaluate the safety and preliminary efficacy of 225Ac-ABD-147 in patients with SCLC or LCNEC who previously received platinum-based therapy. The study will determine the recommended dose regimen for future development. “FDA clearance of our first IND marks a major milestone for Abdera as we transition into a clinical-stage radiopharmaceutical company,” said Lori Lyons-Williams, president and chief executive officer. “We believe our ROVEr™ platform uniquely enables a new wave of innovation in targeted radiotherapeutics, with ABD-147 representing the first in a robust pipeline of custom-engineered programs we are advancing to the clinic.” About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed. About ABD-147 ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy. About the ROVEr™ Platform Abdera’s Radio Optimized Vector Engineering (ROVEr™) platform enables the company to custom-engineer targeted radiopharmaceuticals with tunable pharmacokinetic (PK) properties to achieve high tumor uptake while minimizing renal exposure and mitigating other systemic radiotoxicities such as myelosuppression. Abdera can optimize the delivery and therapeutic index of potent radioisotopes capable of emitting powerful alpha or beta particles to selectively destroy tumor cells while sparing healthy cells, providing patients with potentially transformative new cancer treatments. Abdera’s approach offers the ability to design radiotherapeutics against virtually any cancer target expressed on the cell surface. Coupled with a highly potent mechanism of cell killing, the ROVEr platform is uniquely poised to exploit both high- and low-expressing targets to selectively deliver therapeutic levels of radioisotope to cancer cells. About Abdera Abdera Therapeutics is a biopharmaceutical company leveraging antibody engineering to design and develop new precision radiopharmaceuticals for cancer. Abdera’s Radio Optimized Vector Engineering (ROVEr™) platform enables the company to engineer potential best-in-class therapies for both clinically validated and novel targets that deliver potent radioisotopes capable of emitting alpha or beta particles to selectively destroy cancer cells. Abdera’s lead program, ABD-147, is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac) to solid tumors expressing delta-like ligand 3 (DLL3) for the treatment of small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC). Headquartered in South San Francisco, CA, Abdera also has offices in Vancouver, British Columbia, Canada. To learn more, please visit and follow us on LinkedIn and X.