New therapy bests chemo at improving survival in endometrial cancer
Trial testing Merck's sac-TMT in patients with hard-to-treat cancer hits main goal
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A large clinical trial testing Merck’s therapy candidate sacituzumab tirumotecan (sac-TMT) in people with hard-to-treat endometrial cancer has achieved its main goal, with sac-TMT outperforming standard chemotherapy in delaying disease progression and prolonging survival.
That’s according to new data from the global Phase 3 TroFuse-005 study (NCT06132958), which is testing the experimental therapy versus chemo in about 700 people with advanced endometrial cancer.
Merck announced in a company press release that the trial “met its primary endpoints of overall survival (OS) and progression-free survival (PFS) in certain patients with advanced or recurrent endometrial cancer,” noting “statistically significant improvement in both OS and PFS compared to chemotherapy.” Progression-free survival is the time patients remain alive without the disease advancing.
“These results show sac-TMT may be able to address a critical unmet need for certain patients with advanced endometrial cancer, one of the only cancers increasing in both incidence and mortality worldwide,” said Domenica Lorusso, MD, PhD, global lead investigator of the clinical trial at Humanitas University and Humanitas San Pio X in Italy.
Endometrial cancer is a form of gynecological cancer marked by the abnormal growth of cells that line the uterus. Currently available treatments include platinum-based chemotherapy, which targets rapidly dividing cells, and anti-PD-1/L1 immunotherapy, which directs immune cells to attack the tumor.
When these standard therapies fail to control the cancer, however, options are limited.
This trial, slated for completion in 2028, enrolled cancer patients who had previously received platinum-based chemotherapy and anti-PD-1/anti-PD-L1 immunotherapy, either together or separately. Participants were randomly assigned to treatment with either sac-TMT or their doctor’s choice of standard chemotherapies.
Endometrial cancer can advance despite chemo, immunotherapy
The study’s main goals were to determine whether sac-TMT improved overall survival and progression-free survival compared with standard chemo. According to Merck, an interim analysis showed the experimental therapy led to statistically significant improvement in both overall and progression-free survival relative to standard treatment. The study also met a key secondary endpoint of objective response rate, and safety data were consistent with prior studies of sac-TMT, per Merck.
Merck’s announcement did not provide details on any of these outcomes. The company noted that in-depth results will be presented at an upcoming medical meeting and discussed with global regulatory authorities.
“These findings reinforce our belief that sac-TMT … has the potential to become a cornerstone in the treatment of certain patients with advanced endometrial cancer. We thank the patients and investigators for participating in our studies,” said Dean Y. Li, MD, PhD, president of Merck Research Laboratories, noting that sac-TMS is “being developed in collaboration with Kelun-Biotech.”
Despite recent advances, [cancer] patients whose disease progresses following treatment with platinum and immunotherapy are urgently in need of new options, and these findings show for the first time that [sac-TMT] may be an effective option.
Sac-TMT belongs to a class of anticancer therapies known as antibody-drug conjugates (ADCs). Essentially, ADCs consist of an antibody that targets a cancer protein, attached to a cell-killing toxin. The idea is that the antibody will deliver the toxin directly to cancer cells, thus killing them. The antibody used in sac-TMT specifically targets a protein called TROP2.
“Despite recent advances, patients whose disease progresses following treatment with platinum and immunotherapy are urgently in need of new options, and these findings show for the first time that a TROP2 ADC may be an effective option in this setting,” Lorusso said.
Merck is running more than a dozen Phase 3 clinical trials testing various regimens using sac-TMT in a wide variety of cancers, including other studies in endometrial cancer. The therapy is also being tested for other types of gynecological cancer, including cervical and ovarian cancers.
