Merck Tests ADCs Alone and With Keytruda Across Breast and Gynecologic Cancers
核心洞察
Merck (搜索) is running more than 20 clinical trials in breast and gynecologic cancers involving nearly 20,000 patients worldwide, pairing antibody-drug conjugates with Keytruda.
Lead investigational ADC sacituzumab tirumotecan targets Trop2 (搜索) and met both primary endpoints in a phase 3 endometrial cancer (搜索) trial, improving overall and progression-free survival.
Merck (搜索)'s women's oncology pipeline also includes ifinatamab deruxtecan, patritumab deruxtecan and raludotatug deruxtecan, developed with Daiichi Sankyo.
Merck (搜索) is testing its antibody-drug conjugates (ADCs) as monotherapy and in combination with its immunotherapy Keytruda across breast cancer and several gynecologic cancers, including endometrial, ovarian and cervical cancer (搜索). The program spans more than 20 clinical trials in breast and gynecologic cancers involving nearly 20,000 patients worldwide, according to Dr. Shweta Jain, vice president of global clinical development at Merck.
The strategy reflects the drugmaker's aim of replacing chemotherapy in these settings. "Our aim is to essentially see how you could replace chemotherapy, how you could partner with Keytruda to ultimately make the regimens even more efficacious and continue to improve the tolerability profile," Jain said.
Sac-TMT Meets Both Primary Endpoints in Endometrial Cancer
Merck (搜索)'s lead investigational ADC in women's oncology is sacituzumab tirumotecan (sac-TMT), which targets Trop2 (搜索), a protein involved in cell growth. The drug recently met both primary endpoints in a phase 3 trial, significantly improving overall and progression-free survival in patients with advanced or recurrent endometrial cancer (搜索) whose disease had progressed after treatment with chemotherapy and immunotherapy. Merck plans to share additional data from that trial this year or next year.
"Endometrial is particularly underserved," Jain said. It is one of only a few cancers with a rising mortality rate, and it disproportionately affects Black women, who die at twice the rate of white women, according to the American Cancer Society.
Merck (搜索) has set up 17 phase 3 studies of sac-TMT across different tumor types, including trials targeting lung, digestive and genitourinary cancers. Within the women's cancer division, studies are exploring sac-TMT as monotherapy and in combination in endometrial cancer (搜索), ovarian cancer (搜索), cervical cancer (搜索), hormone-positive breast cancer and triple-negative breast cancer (搜索).
A Broader Women's Oncology Pipeline
Sac-TMT sits within a wider pipeline that also includes ifinatamab deruxtecan and patritumab deruxtecan, which are being tested in breast, cervical, endometrial and ovarian cancers. Raludotatug deruxtecan, which Merck (搜索) is developing with Daiichi Sankyo, is in the phase 3 portion of a phase 2/3 ovarian cancer (搜索) study and in a phase 2 study that includes endometrial and cervical cancers.
Keytruda serves as a backbone of the program. "With antibody drug conjugates, combining them with immuno-oncology therapies makes sense," Jain said. "That's what we are going to explore with our antibody drug conjugate platform."
Interest in ADCs has risen across the pharmaceutical industry with the success of drugs such as Daiichi Sankyo and AstraZeneca's Enhertu. ADCs pair a tumor-targeting antibody with a potent drug payload that mostly hits cancerous cells while limiting effects on healthy tissue, a mechanism sometimes described as "smart chemotherapy." Merck (搜索) faces competition from AstraZeneca, which is looking to expand indications for Enhertu and another ADC, Datroway, while Gilead is testing Trodelvy for new indications in endometrial and ovarian cancer (搜索).
Precision Diagnostics and Therapeutic Window
As oncology moves toward targeted strategies, Merck (搜索) is applying diagnostic tools to determine which patients will most benefit from a given therapy and the appropriate therapeutic window. "That has become more and more the focus as we set up our development programs within women's cancer. It's not just about defining who responds, but it's also about correctly identifying the right therapeutic window," Jain said.
Jain framed the clinical goal in terms of tolerability as well as survival. "Can you improve the outcomes without adding a significant toxicity burden on the patients?" she said, adding that success in women's oncology is not only about buying patients more time but making those added months or years feel as close to normal as possible.
Unmet Need and Market Context
Unmet need in these tumors remains substantial. Gynecologic cancers caused more than 600,000 deaths globally in 2024. PwC estimates that the broader female-specific oncology market, including therapeutics, devices and diagnostics, and care delivery, could reach $100 billion to $110 billion by 2030.
Merck (搜索) intends to continue advancing the portfolio in women's cancer. "I think broadly speaking, we are going to advance our portfolio, continue to focus again in women's cancer, where we've understood what the disease biology is and how it can be responsive to different types of pathways," Jain said.