Tarlatamab

Virginia cancer centers offer advanced care, including NCI-designated comprehensive centers, updated technology, and expanding facilities, ensuring patients need not travel out of state for treatment.

Amgen presents new data on IMDELLTRA™ (tarlatamab-dlle), a DLL3-targeting BiTE® molecule, at the 2024 WCLC, highlighting its efficacy in extensive-stage small cell lung cancer (ES-SCLC) as both a monotherapy and in combination with PD-L1 inhibitors.

Heavily pretreated ES-SCLC patients benefited from ifinatamab deruxtecan (I-DXd), with a 12 mg/kg dose showing higher overall response rate (54.8%) vs. 8 mg/kg (26.1%). Disease control rates were over 80% in both groups, suggesting I-DXd's potential as a treatment option for ES-SCLC.

Extended follow-up of DeLLphi-300 trial shows tarlatamab, a bispecific T-cell engager, benefits previously treated small cell lung cancer patients with 25.0% objective response rate, 11.2 months median duration of response, and 17.5 months median overall survival. At recommended 10 mg every 2 weeks, 35.3% response rate, 14.9 months median duration, 20.3 months median survival, and 29.4% sustained disease control at ≥ 52 weeks. Intracranial activity observed in 62.5% with baseline CNS lesions ≥ 10 mm.

Bispecific antibodies, with two binding domains, offer targeted therapeutics and address co-administration challenges, gaining traction in biopharma. Initially approved for cancer, they now target various diseases, with 12 approved in the U.S. and more in development. Their dual action reduces patient burden and enhances treatment effects, potentially transforming therapeutic paradigms beyond oncology. The market is projected to grow significantly due to rising chronic disease incidence and technological advancements.

Dr. Himisha Beltran discussed DLL3 as a therapeutic target for neuroendocrine prostate cancer at the 2024 ESMO Congress. DLL3 expression increases in castrate-resistant prostate cancer and is crucial for maintaining a neuroendocrine phenotype. Despite early promising results with DLL3-targeted therapies like Rova-T, efficacy was limited and toxicity high. Ongoing DLL3-targeted therapies include T cell engagers, ADCs, radionuclides, and CAR-T. Tarlatamab, a DLL3-targeted bi-specific T cell engager, showed limited efficacy in neuroendocrine prostate cancer. MK-6070, another DLL3-targeted T cell engager, demonstrated strong anti-tumor activity in neuroendocrine prostate cancer models. Future PET imaging with ⁸⁹Zr-SC16 may aid in patient selection and resistance pattern understanding.

Sally Lau, MD, discusses her role in the DeLLphi-304 trial, focusing on the accelerated approval of Imdelltra for relapsed small-cell lung cancer. She highlights the importance of nurse navigators and diversity grants in supporting patient enrollment and retention in trials, emphasizing the need for early involvement and responsive sponsors. Lau's passion for clinical trials stems from witnessing direct patient benefits and innovative treatment approaches.

Ifinatamab deruxtecan (I-DXd) showed improved efficacy in heavily pretreated extensive-stage small cell lung cancer (ES-SCLC) patients, with a 12-mg/kg dose achieving a 54.8% overall response rate (ORR) vs 26.1% for an 8-mg/kg dose. The 12-mg/kg dose also had a 90.5% disease control rate (DCR) and a median duration of response (DOR) of 4.2 months, compared to 7.9 months for the 8-mg/kg dose. Both doses were generally well-tolerated, with gastrointestinal and hematologic toxicities as the primary adverse effects.

FDA approved Amgen's Imdelltra for advanced small-cell lung cancer, offering hope as a second-line treatment. Clinical trials show it reduces tumor growth and extends life. Small-cell lung cancer, comprising 15% of lung cancer cases, has a low survival rate. Patients like Lynne Bell report significant improvement with Imdelltra.