Becoming a blockbuster in its third full year on the market put Gilead’s cancer treatment Trodelvy on a course to potentially justify the company’s $21 billion buyout of Immunomedics in 2020. But lately there have been just about as many misses as hits for the first-in-class TROP-2-directed antibody-drug conjugate (ADC).
Another miss came Friday as Gilead revealed that Trodelvy has whiffed as a first-line treatment for patients with HR+/HER2-negative metastatic breast cancer. Without revealing data, the company said that the phase 3 Ascent-07 study comparing Trodelvy to chemotherapy failed to meet its primary endpoint of progression-free survival (PFS).
On a positive note, regarding the key secondary endpoint of overall survival, Gilead said that an early trend was observed favoring patients who were treated with Trodelvy. The company added that the data are not mature and will continue to be assessed.
Participants in the trial had locally advanced, inoperable or HR+/HER2-negative metastatic breast cancer and had received prior endocrine therapy. The study enrolled 654 patients across nearly 30 countries, who were randomized at a 2-to-1 rate in favor of Trodelvy. Patients in the control arm received a physician’s choice of cytotoxic chemotherapy.
“HR+/HER2-negative metastatic breast cancer is a highly heterogeneous disease, and this complexity makes it particularly challenging to manage, especially in patients whose disease has already progressed on multiple lines of endocrine therapy,” Hope Rugo, M.D., the director of the Women’s Cancer Program at City of Hope and the trial’s principal investigator, said in a release. “It will be critical that we continue to follow patients for overall survival to better understand the potential impact of [Trodelvy] long-term in this treatment setting.”
It's another setback for Trodelvy, which was described as a “transformative cornerstone therapy,” by Gilead CEO Daniel O’Day when the company gained it in the Immunomedics transaction.
The FDA originally endorsed Trodelvy on an accelerated basis in 2020 as a treatment for previously-treated metastatic triple negative breast cancer (TNBC) and upgraded the nod a year later when a confirmatory trial showed that it was the first treatment in the indication to improve PFS and OS.
Gilead has had difficulty, however, advancing Trodelvy in other treatment settings. Last year, the company withdrew its 2021 accelerated approval for Trodelvy to treat bladder cancer after the failure of a confirmatory trial.
Also last year, Trodelvy failed to top chemotherapy in a high-profile study of patients with previously treated metastatic non-small cell lung cancer (NSCLC). With the trial miss, Gilead took a $2.4 billion impairment charge.
On the flip side, there have been trial victories this year as Trodelvy bested chemotherapy at extending the time before disease worsening or death in certain patients with previously untreated metastatic triple-negative breast cancer (TNBC) who were not eligible for immunotherapy in the Ascent-03 study.
Additionally, in the Ascent-04 study, a combination of Trodelvy and Merck’s Keytruda lowered the risk of progression or death by 35% versus a combination of Keytruda and chemotherapy when used as an initial treatment for metastatic triple-negative breast cancer (TNBC) that expresses PD-L1.
In the market, Trodelvy faces potential competition with Daiichi Sankyo and AstraZeneca’s Datroway. Last week, Gilead reported sales of Trodelvy at $1.01 billion for the first three quarters of this year, which was a 4% increase year over year.