Following the news that the FDA has accepted the BLA submission for datopotamab deruxtecan in non-squamous NSCLC patients;

Israel Stern, MSc,  Oncology & Hematology Analyst at GlobalData, a leading data and analytics company, offers his view:

“As sales for Daiichi Sankyo’s and AstraZeneca’s HER2+-targeting antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) continue to skyrocket, the companies are poised for yet another anticipated ADC blockbuster with DS-1062, or datopotamab deruxtecan. The ADC contains an anti-TROP2 monoclonal antibody covalently linked to the topoisomerase I inhibitor cytotoxic payload. GlobalData estimates the drug to earn $3.12 billion by 2029.

“The Biologics License Applications (BLA) for datopotamab deruxtecan was accepted on the basis of the Phase III TROPION-Lung01 study, which showed the ADC provided advanced pretreated non-small cell lung cancer (NSCLC) patients without genomic alterations a statistically significant improvement in progression-free survival (PFS) compared with docetaxel chemotherapy. Notably, the non-squamous patient subset had a median PFS of 5.6 months vs. 3.7 months and a numerical improvement in overall survival. The secondary endpoint of the objective response rate was 31.2% versus 12.8% with docetaxel. There’s a parallel BLA for DS-1062 in HR+ and HER2-breast cancer that is pending approval.

“There are multiple Phase III studies for the ADC in frontline NSCLC in combination with immune checkpoint inhibitors such as Merck’s Keytruda (pembrolizumab) or AstraZeneca’s Imfinzi (durvalumab). Enhertu was the first ADC licensed in NSCLC when it gained accelerated approval for patients with HER2 mutations. Several ADCs targeting the TROP2 protein for NSCLC are being investigated. Gilead’s Trodelvy (sacituzumab govetican), marketed for advanced breast and bladder cancer, is seeking a label expansion for first-line NSCLC in combination with Keytruda. Trodelvy alone failed to show meaningful life extension vs. docetaxel in pretreated NSCLC.

“Merck’s MK-2870 (sacituzumab tirumotecan) is a direct competitor to DS-1062 with its ADC in Phase III for non-squamous NSCLC, although it’s at a competitive disadvantage to DS-1062 as it’s specifically indicated for patients withepidermal growth factor receptor other genomic alterations. Other late-stage pipeline ADCs for NSCLC include BMS’ BLB-01D1 targeting HER3 and Abbvie’s ABBV-399 telisotuzumab vedotin targeting c-Met. Daiichi’s deruxtecan technology led to the top-selling ADC as Enhertu racked up $3.4 billion in 2023, and GlobalData projects it to surpass $14 billion by 2029. Apart from DS-1062, the company has four other late-stage ADCs with deruxtecan payloads across a range of solid tumor indications.”