Combining Trodelvy with Keytruda and pushing it into the frontline setting could “potentially double” the ADC’s market in metastatic triple-negative breast cancer, according to analysts at Truist Securities.
The combination of Gilead’s anti-TROP2 antibody-drug conjugate Trodelvy and Merck’s PD-1 blocker Keytruda boosted progression-free survival as a frontline regimen in patients with a highly aggressive form of breast cancer, as per a Monday readout.
Reacting to these findings, analysts at Truist Securities told investors in a Monday note that the late-stage “win” could “potentially double the addressable market” for Trodelvy in metastatic triple-negative breast cancer (mTNBC). Currently, Trodelvy is approved for mTNBC as a monotherapy, and only in patients who have undergone at least two prior lines of systemic therapies.
Gilead did not reveal specific data in its Monday release, only announcing that Trodelvy plus Keytruda “significantly improved” progression-free survival (PFS) as opposed to Keytruda plus chemotherapy. The study, dubbed ASCENT-04/KEYNOTE-D19, involved patients with inoperable or mTNBC whose tumors express the PD-1 marker. More than 440 patients were enrolled in the study.
Data for overall survival, a key secondary outcome, were not available in the readout, though Gilead noted an “early trend in improvement” in favor of the Trodelvy combo. Safety findings were consistent with what had previously been established for Trodelvy and Keytruda separately. ASCENT-04 did not document new signals of concern.
Gilead plans to share Monday’s results with regulatory authorities and present detailed findings at an upcoming scientific meeting.
Approval for this Trodelvy regimen in this indication is expected in 2026, according to the Truist analysts, who noted that if it wins regulatory clearance, it could “eventually face competition” from emerging PD-L1 combination therapies, particularly those that also use VEGF blockers.
Of these, the Truist analysts specifically named Summit Therapeutics and its development partner Akeso, which in September 2024 shook the space with a Phase III readout from their HARMONi-2 study, claiming that their bispecific antibody ivonescimab beat Keytruda as a frontline therapy for non-small cell lung cancer (NSCLC).
Ivonescimab works by targeting both the PD-1 and VEGF pathways, in turn disrupting cancer cells’ ability to evade the immune system and preventing the formation of new blood vessels that would otherwise enrich the tumor. Last year’s readout also showed that ivonescimab bested Keytruda in various patient subgroups, though analysts were measured in their optimism, highlighting the need for more robust overall survival findings and more diverse data.
BioNTech is also playing in this space, announcing last month that its own PD-1/VEGF bispecific BNT327 led to a confirmed objective response rate of more than 85% in a Phase II NSCLC study.
