Gilead Sciences' TROP2-directed drug Trodelvy (sacituzumab govitecan) has failed to outperform chemotherapy in the TROPiCS-04 study, a clinical trial aimed at evaluating its efficacy as a second-line treatment for patients with locally advanced or metastatic urothelial carcinoma (UC) who have previously undergone chemotherapy and immunotherapy with PD-1/PD-L1 inhibitors. The study revealed that Trodelvy did not extend patients' lives more effectively than chemotherapy, a setback for Gilead as this trial was intended to confirm the drug's accelerated approval for previously-treated UC granted by the FDA in 2021.
Moreover, the trial reported a higher number of deaths due to adverse events in the Trodelvy group compared to the chemotherapy group, primarily due to neutropenia. Gilead is emphasizing the importance of G-CSF use to prevent neutropenic complications among treating physicians and is analyzing the data further to discuss the results and next steps with the FDA.
This failure follows another recent disappointment for Trodelvy in the EVOKE-01 study, where it did not improve overall survival compared to chemotherapy in previously treated non-small cell lung cancer (NSCLC). Despite these setbacks, Gilead is investigating a potential trend towards improvement in a subgroup of patients who did not respond to prior immunotherapy, with new data from EVOKE-01 expected to be presented at the ASCO congress. Additionally, results from the phase 2 EVOKE-02 study, examining Trodelvy in combination with MSD’s Keytruda (pembrolizumab) for first-line PD-L1-high NSCLC, will also be shared.
Gilead faces increasing competition in the TROP2 ADC category from AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan (Dato-DXd) and MSD/Kelun’s sacituzumab tirumotecan, both of which are advancing in their respective indications. Trodelvy is currently FDA-approved for previously treated metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive/HER2-negative metastatic breast cancer, but its position is becoming increasingly vulnerable as competitors make significant strides in similar therapeutic areas.
