Lilly presents first clinical data for its investigational, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting
- Promising 55% overall objective response rate at recommended Phase 2 dose
- Demonstrated efficacy across all FRα expression levels, expanding potential patient population
- Strong 74% disease control rate in efficacy-evaluable patients
- No treatment-emergent neuropathy or ocular toxicity observed
- Showed efficacy in patients who previously failed mirvetuximab soravtansine treatment
- Still in early Phase 1 stage of development
- Common adverse events include nausea (64%), anemia (40%), and other side effects
- Maximum tolerated dose has not yet been established
Insights
Lilly's new ADC shows promising 55% response rate in hard-to-treat ovarian cancer patients regardless of biomarker levels.
The Phase 1 data for Lilly's folate receptor alpha (FRα) antibody-drug conjugate (LY4170156) represents a significant development in ovarian cancer treatment. The 55% objective response rate at the recommended Phase 2 dose is particularly impressive for platinum-resistant ovarian cancer, a notoriously difficult-to-treat condition. What makes these results especially promising is the activity across all FRα expression levels, including in patients previously treated with mirvetuximab soravtansine (another FRα-targeting therapy).
The drug's efficacy profile could potentially address a major limitation of current FRα-targeting treatments - the need for high biomarker expression. With 51% of enrolled patients having FRα expression below 75%, the drug's activity across expression levels suggests it could benefit a broader patient population than existing therapies.
The safety profile appears manageable with primarily gastrointestinal and hematologic events. Notably absent are treatment-emergent neuropathy and ocular toxicity, which have been problematic with other ADCs. This favorable toxicity profile could potentially allow for longer treatment duration or combination approaches.
The heavily pretreated nature of the study population (median of five prior treatment regimens) makes these results even more clinically meaningful, as these patients typically have limited therapeutic options and poor outcomes. Lilly's plans to rapidly advance to Phase 3 trials indicate confidence in the drug's potential, though larger studies will be needed to confirm these preliminary findings and establish durability of response.
Lilly's ADC data represents a potential competitive advantage in the rapidly evolving ovarian cancer market. The 45% overall response rate across all dose levels and 55% at the recommended Phase 2 dose positions this candidate favorably against existing therapies, particularly given the activity in patients previously treated with mirvetuximab soravtansine.
The drug's differentiated profile - an Fc-silent antibody with exatecan payload and proprietary cleavable polysarcosine linker - appears to deliver improved therapeutic outcomes without the ocular and neurological toxicities that have limited other ADCs. This technological advancement could give Lilly an edge in the competitive ADC landscape.
Most significantly, the efficacy across all FRα expression levels addresses a key limitation of current targeted therapies, potentially expanding the eligible patient population substantially. With 51% of trial participants having FRα expression below 75%, this broader efficacy profile could translate to a larger commercial opportunity than biomarker-restricted competitors.
Lilly's decision to expedite development directly to registrational Phase 3 trials signals strong internal confidence in the asset. If successful, this ADC could become a foundational therapy in platinum-resistant ovarian cancer treatment, a market with significant unmet need and commercial potential. The company's focus on advancing its oncology pipeline with novel modalities like ADCs aligns with industry trends toward precision medicine approaches with improved safety profiles.
"ADCs have begun to change the treatment paradigm for some women with ovarian cancer, but a large proportion of patients still have a significant need for new therapies that improve outcomes regardless of FRα expression level," said Isabelle Ray-Coquard, M.D., Ph.D., president of the ENGOT (European Network of Gynecological Oncology Trial) group, medical oncologist at the Centre Léon Bérard Lyon France and principal investigator for the trial. "These initial data show activity across all doses and levels of FRα expression, including in patients previously treated with a FRα targeting treatment. Taken together with the emerging safety and tolerability profile, these data demonstrate early potential to meaningfully improve outcomes for women living with advanced ovarian cancer."
As of the March 9, 2025 data cutoff, the study enrolled 95 participants with high-grade serous ovarian cancer across four dose levels (2 - 6 mg/kg). Patients received a median of five prior systemic regimens (range 1-10), and
Efficacy results demonstrate responses at all dose levels, across all FRα expression levels, including in patients who progressed on prior mirvetuximab soravtansine. In the 58 efficacy-evaluable patients (37 patients remain ongoing prior to first response assessment and were therefore not yet efficacy-evaluable at the time of the data cutoff), the ORR was
"We are excited to share these first clinical data for our FRα targeting ADC, demonstrating a promising tolerability and efficacy profile across all FRα expression levels," said David Hyman, M.D., Chief Medical Officer, Lilly. "Based on these results, we believe there is the potential to significantly expand the number of ovarian cancer patients who could benefit from a FRα ADC. We are now focused on rapidly advancing this potential new medicine into registrational Phase 3 clinical trials."
For more information on Lilly's oncology pipeline click here.
About LY4170156
LY4170156 is an investigational, next-generation antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). FRα is a cell-surface glycoprotein encoded by the gene FOLR1 that binds to the essential nutrients folic acid and reduced folates, bringing them into cells to facilitate cell division and growth.1,2 FRα is overexpressed in many solid tumors such as ovarian, non-small cell lung, and colorectal cancers.1,3,4
LY4170156 was designed to target FRα across expression levels with an improved therapeutic index. LY4170156 is composed of an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker (PSARlink™). PSARlink's unique structure "masks" the cytotoxic molecules enabling them to stay in the body longer, providing the potential to broaden the therapeutic index of ADCs. LY4170156 is currently being studied in patients with ovarian cancer as well as other FRα-expressing solid tumors, NCT06400472.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY
Trademarks and Trade Names
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about preclinical data for an antibody-drug conjugate targeting folate receptor alpha and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that any of these therapies will prove to be a safe and effective treatment or receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
- Bax, Heather J et al. "Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes." British journal of cancer vol. 128,2 (2023): 342-353. doi:10.1038/s41416-022-02031-x Bax HJ, et al. Br J Cancer. 2023;128(2):342-353.
- Scaranti, Mariana et al. "Exploiting the folate receptor α in oncology." Nature reviews. Clinical oncology vol. 17,6 (2020): 349-359. doi:10.1038/s41571-020-0339-5.
- Kalli, Kimberly R et al. "Folate receptor alpha as a tumor target in epithelial ovarian cancer." Gynecologic oncology vol. 108,3 (2008): 619-26. doi:10.1016/j.ygyno.2007.11.020.
- Viricel W, et al. Cancer Res. 2023;83(suppl 7):1544.
Refer to: | Megan Talon; megan.talon@lilly.com; 463-209-1470 (Media) | |
Michael Czapar; czapar_michael_c@lilly.com; 317-617-0983 (Investors) |
View original content to download multimedia:https://www.prnewswire.com/news-releases/lilly-presents-first-clinical-data-for-its-investigational-next-generation-fr-targeting-adc-in-platinum-resistant-ovarian-cancer-at-the-2025-asco-annual-meeting-302470018.html
SOURCE Eli Lilly and Company
FAQ
What are the Phase 1 results of Lilly's new ovarian cancer drug LY4170156?
What are the main side effects of Lilly's FRα ADC treatment?
How many patients were included in Lilly's FRα ADC ovarian cancer trial?
What makes Lilly's FRα ADC different from existing treatments?
What is the next step for Lilly's ovarian cancer drug development?
