A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4170156, an Antibody-Drug Conjugate Targeting Folate Receptor α-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors

Overview

LY4170156 is an investigational antibody–drug conjugate (ADC) from Eli Lilly that targets folate receptor alpha (FRα). A first‑in‑human, multicenter Phase 1a/1b study (NCT06400472; LOXO‑FRA‑24001) is ongoing across multiple tumor types with FRα expression. Initial clinical data in platinum‑resistant ovarian cancer (PROC) were presented at the 2025 ASCO Annual Meeting; Lilly reported preliminary anti‑tumor activity with a 55% objective response rate (ORR) at the putative recommended Phase 2 dose (RP2D) of 4 mg/kg. As of the March 9, 2025 cutoff, 95 patients with high‑grade serous ovarian cancer had been enrolled, including individuals previously treated with mirvetuximab soravtansine. (investor.lilly.com)

Mechanism of action

• Target: Folate receptor alpha (FRα), an internalizing cell‑surface glycoprotein encoded by FOLR1 that is overexpressed in several epithelial tumors (e.g., ovarian, NSCLC, colorectal). (investor.lilly.com)
• Construct: Fc‑silent humanized IgG1 anti‑FRα antibody conjugated to the topoisomerase I inhibitor exatecan via a cleavable polysarcosine linker (PSARlink). The conjugate is reported to have a homogeneous drug–antibody ratio (DAR) of 8. Dosing in the Phase 1 trial is every 3 weeks (Q3W). (oncologypro.esmo.org)

Efficacy

• ASCO 2025 (Phase 1a/1b, PROC): Lilly reported a preliminary ORR of 55% at the proposed RP2D (4 mg/kg), with activity observed across dose levels and FRα expression strata, including in patients previously treated with mirvetuximab soravtansine. Enrollment at data cutoff was 95 patients; key endpoints include safety, PK, and anti‑tumor activity per RECIST v1.1. (investor.lilly.com)
• Additional reporting from trade outlets covering the ASCO poster noted, among 58 efficacy‑evaluable patients, an overall ORR of 45% and disease control rate of 74%, with the 55% ORR at 4 mg/kg highlighted by Lilly. (These figures derive from meeting‑related communications rather than a peer‑reviewed publication.) (pharmexec.com)

Overall, no peer‑reviewed, full manuscripts of clinical results were identified as of October 7, 2025.

Safety

• Lilly described an “encouraging safety profile” in the Phase 1 study; detailed adverse‑event rates have not been fully disclosed publicly. The study’s primary objectives include determination of RP2D and safety/tolerability; ocular comorbidity exclusions (e.g., corneal keratopathy) are specified in the protocol. (investor.lilly.com)

Ongoing development

• Trial design includes dose‑escalation/optimization and expansion cohorts across ovarian and other FRα‑expressing solid tumors, with monotherapy and combination cohorts (e.g., with bevacizumab or carboplatin). Global recruitment is ongoing. (oncologypro.esmo.org)

Further reading

• Lilly press release summarizing first clinical data (ASCO 2025): Lilly presents first clinical data for its investigational, next‑generation FRα targeting ADC in platinum‑resistant ovarian cancer. (investor.lilly.com)
• ASCO 2025 poster listing: Initial results from a first‑in‑human phase 1 study of LY4170156 (Abstract 3023). (1stoncology.com)
• ESMO 2024 trial‑in‑progress abstract (design/mechanism details; Abstract 795TiP). (oncologypro.esmo.org)
• Trial information and U.S. site listing (NCT06400472 – UCSD portal). (clinicaltrials.ucsd.edu)
• Lilly Oncology pipeline page for NCT06400472 (cohort structure and key criteria). (lillyoncologypipeline.com)

Note: Because available data are from early‑phase conference materials and company communications, findings should be considered preliminary until validated in peer‑reviewed publications or later‑phase trials.

Last updated: Oct 2025

Inclusion Criteria:

* Have one of the following solid tumor cancers:

* Cohort A1: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) cancer, endometrial cancer, cervical cancer, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), pancreatic, and colorectal cancer (CRC)

* Cohort A2/A3/A4/A5/B1/B2: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) cancer

* Cohort C1/C2: Endometrial cancer, cervical cancer, NSCLC, TNBC, CRC or pancreatic cancer

Exclusion Criteria:

* Individual with known or suspected uncontrolled central nervous system (CNS) metastases

* Individual with history of carcinomatous meningitis

* Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection

* Individual with evidence of corneal keratopathy or history of corneal transplant

* Any serious unresolved toxicities from prior therapy

* Significant cardiovascular disease

* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms)

* History of pneumonitis/interstitial lung disease

* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention