Pivotal Merck/Kelun TROP2 studies seek nearly 10,000 patients

As if Merck & Co’s desire to take on Daiichi Sankyo/AstraZeneca in the TROP2-targeting ADC space was in any doubt, yet another phase 3 study of sacituzumab tirumotecan has just been listed on clinical trials registries. This will test the Kelun-originated anti-TROP2 ADC as maintenance after Keytruda plus chemo in first-line squamous NSCLC, and seeks to recruit 851 patients. It takes the number of Merck-sponsored pivotal trials of the project to nine, versus Kelun’s five, and the total number of patients to be enrolled into these efforts now stands at a remarkable 9,367. That’s an enormous bet to put on an asset for which Merck paid Kelun just $47m two years ago. For their part, Daiichi/Astra have so far taken datopotamab deruxtecan into 12 phase 3 studies, and two settings are already before the FDA: the agency is to rule on approval for second-line non-squamous NSCLC (Tropion-Lung01 study) in December, and on use in second-line ER-positive HER2-negative breast cancer (Tropion-Breast01) in February 2025. Pivotal trials of sacituzumab tirumotecanStudySettingDesignPrimary endpointsEnrolmentGlobal studies sponsored by Merck...MK-2870-019Adjuvant stage II-IIIB NSCLCKeytruda combo, vs KeytrudaDFS780MK-2870-0071L PD-L1 ≥50% NSCLCKeytruda combo, vs KeytrudaOS614MK-2870-0231L maintenance in squamous NSCLCKeytruda/chemo combo, vs KeytrudaOS851MK-2870-0042L+ EGFR+ve & other genetically altered* non-squamous NSCLCVs pemetrexed or docetaxelPFS & OS556MK-2870-0092L+ (post EGFR TKIs) EGFR+ve non-squamous NSCLCVs pemetrexed + carboplatinPFS & OS520MK-2870-012Adjuvant TNBCKeytruda combo, vs Keytruda +/- chemoiDFS1,530MK-2870-0102L+ ER+ve HER2-ve breast cancer+/- Keytruda, vs physician’s choicePFS1,200MK-2870-0052L endometrial cancerVs chemoPFS & OS710MK-2870-0153L+ gastroesophageal adenocarcinomaVs physician’s choiceOS450...and those with an Asia focus, sponsored by KelunSKB264-III-121L PD-L1 ≥1% NSCLCKeytruda combo, vs KeytrudaPFS646SKB264-III-092L+ (post EGFR TKIs) EGFR+ve non-squamous NSCLCVs pemetrexed + carboplatinPFS356SKB264-III-111L TNBCVs chemoPFS & OS524SKB264-III-102L+ ER+ve HER2-ve breast cancerVs physician’s choicePFS376SKB264-III-03/ OptiTROP-Breast013L+ TNBCVs physician’s choicePFS254Note: *includes NSCLC driven by mutations in ALK, ROS1, BRAF, NTRK, MET or RET. Source: OncologyPipeline.