Even as Gilead looks to become an oncology powerhouse in the coming years, the company on Monday recorded a major setback for its antibody-drug conjugate (ADC) Trodelvy.
The company’s phase 3 EVOKE-1 trial showed that Trodelvy didn't significantly extend the lives of patients with previously treated metastatic non-small cell lung cancer (NSCLC) when pitted against the chemotherapy docetaxel. With that, the trial failed to meet its primary endpoint, Gilead said Monday.
Despite the fail, the “totality of our data” gives the company “continued confidence” in Trodelvy’s potential in the population, chief medical officer Merdad Parsey, M.D., Ph.D. said in the company’s press release.
“Treating metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges and the need for safe and effective treatments remains urgent," Parsey added.
The full data will be presented at an upcoming medical meeting and Gilead plans to discuss the trial results with regulators, the company said.
As Gilead works to grow in oncology, the company has put much of its attention into its ADC drug Trodelvy and the cell therapies Yescarta and Tecartus. The historically HIV-focused drugmaker has set a goal to pull one third of its revenue from its oncology products by 2030. Trodelvy is the first FDA-approved TROP2-directed ADC that can work in two different types of metastatic breast cancers, the company pointed out.
Now, the NSCLC miss could spell trouble for Trodelvy. As it stands, the ADC’s breast cancer market share is limited to previously treated HR-positive, HER2-negative patients, as well as triple-negative cases. But Daiichi Sankyo and AstraZeneca’s rival HER2-directed ADC Enhertu, and its groundbreaking approval in new breast cancer category HER2-low, puts pressure on Gilead’s offering.
The HER2-low category not only widens Enhertu’s treatment population but could stand to shrink Trodelvy’s share as more tumors are classified as HER2-low and fall into Enhertu eligibility, Leerink Partners analysts have said. The HER2-low description makes up 60% of U.S. breast cancer diagnoses that were previously classified as HER2-negative, according to the FDA.
Enhertu's competition means expanding Trodelvy's use in NSCLC is key to keeping up, making the latest loss all the more troublesome for Gilead.
The company is also exploring the med’s potential in head and neck cancer, gynecological cancer, and gastrointestinal cancers, according to the release. A phase 3 study in first-line metastatic PD-L1 high NSCLC is currently enrolling.
Trodelvy's trial flop sent Gilead shares tumbling about 10% on Monday after they reached an 11-month high, MarketWatch reports.
Despite the industry's ADC enthusiasm, some safety concerns have come to light recently, especially with a common side effect of interstitial lung disease (ILD). Daiichii Sankyo and AstraZeneca recently reported seven ILD patient deaths in a study of their TROP2 ADC Dato-DXd, four of which were due to disease progression.
However, several factors may have contributed to the deaths, including pre-treatment, Daiichi’s head of oncology clinical development Mark Rutstein, M.D., hypothesized in an interview with Fierce Biotech at 2023’s European Society for Medical Oncology (ESMO) Congress in Madrid. The drug still pulled out a statistically significant benefit in the reduction of disease progression or death in its NSCLC study, which came out to 25% compared to docetaxel. The overall risk-benefit profile still seemed in Daxo-DXd’s favor, Rutstein added.
Gilead tracked no new safety signals in its EVOKE-1 study of 601 patients.