Ifinatamab deruxtecan

Small cell lung cancer, a fast-growing and aggressive subtype, accounts for 10-15% of lung cancer cases globally. It has limited-stage and extensive-stage classifications, with poor prognosis due to early metastasis. Primary cause is long-term tobacco exposure, leading to rapid tumor growth. First-line therapies include platinum-based chemotherapy with radiotherapy for limited-stage, and platinum-based chemotherapy plus immunotherapy for extensive-stage. Immune checkpoint inhibitors and antibody-drug conjugates are advancing treatment, offering hope for relapsed and refractory cases.

AstraZeneca and Daiichi Sankyo's Dato-DXd received FDA Breakthrough Therapy designation for EGFRm NSCLC, based on phase II and III study data. They submitted a new BLA for accelerated approval in this indication and withdrew an earlier BLA for nonsquamous NSCLC. Dato-DXd is also under review for HR+ HER2- breast cancer, with regulatory applications ongoing globally.

FDA grants Merck's sacituzumab tirumotecan (sac-TMT) breakthrough therapy designation for advanced non-squamous NSCLC with EGFR mutations, post-chemotherapy progression. This marks the first BTD for sac-TMT, an ADC developed with Kelun-Biotech, with Merck holding global marketing rights except in Greater China.

At the 2024 WCLC, 7,000+ clinicians and scientists gathered to review impactful abstracts on lung cancer treatments, including novel perioperative strategies for resectable lung cancer and the use of tyrosine kinase inhibitors, bispecific antibodies, and ADCs in advanced NSCLC and SCLC. Key findings included superior event-free survival with perioperative nivolumab, high pathologic response rates with ADCs in localized NSCLC, and promising outcomes with EGFR-MET bispecific antibodies and HER2-targeted therapies. The conference also highlighted the potential of ADCs in SCLC and the need for improved biomarker development and patient selection tools.

Daiichi Sankyo and AstraZeneca awarded 2024 Prix Galien USA for Enhertu, a HER2-directed ADC. Enhertu, developed jointly, is transforming HER2+ solid tumour treatment. The Galien Foundation recognizes impactful FDA-approved treatments, honoring medical innovation.

Recent lung cancer meetings showcased ADCs compared to PD-1/PD-L1 inhibitors, with ivonescimab (AK112) showing improved PFS in PD-L1+ NSCLC. An ADC also demonstrated better PFS and response rates than pembrolizumab. In extensive-stage small cell lung cancer, ifinatamab deruxtecan showed dose-response benefits, suggesting potential for targeted therapies.

Charles Rudin presented groundbreaking data on ifinatamab deruxtecan (I-DXd, DS-7300), an antibody drug conjugate (ADC) showing impressive response rates in extended stage SCLC at 8 mg/kg (26%) and 12 mg/kg (56%). Potential synergies with immunotherapy due to immunogenic cell death induction. Modern protein engineering enables targeting multiple tumor antigens with bispecific antibodies, promising future advancements in targeted therapies.

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.

The global ADC market is rapidly expanding, driven by increasing demand for targeted therapies. Over 15 ADCs are approved, with more than 600 in clinical trials. At least 10 new approvals are expected in the next couple of years. Numerous ADC candidates are in pivotal stages, with over 20 in Phase 3 trials. Key drugs in late-stage trials include Ifinatamab deruxtecan, DP 303c, BL B01D1, 9MW 2821, Telisotuzumab vedotin, and Datopotamab deruxtecan.

Daiichi Sankyo and MSD report Phase III HERTHENA-Lung02 trial of patritumab deruxtecan met primary endpoint of progression-free survival in EGFR-mutated NSCLC patients. The trial showed a significant PFS improvement for patritumab deruxtecan versus chemotherapy, with a safety profile consistent with previous studies.