LY4170156 / Eli Lilly - LARVOL DELTA

First patient enrolled in GOG-3133/ FRAmework-01 phase 3 study evaluating sofetabart mipitecan (LY4170156), a novel ADC targeting folate receptor alpha (FRα), in recurrent ovarian cancer (Eurekalert) - "This clinical trial has two parts; it tests a potential new medicine called sofetabart mipitecan for people with certain types of ovarian, peritoneal, and fallopian tube cancers. Part A looks at participants whose cancer no longer responds to platinum-based chemotherapy (platinum resistant). Part B looks at participants whose cancer has a higher chance of responding to platinum-based chemotherapy (platinum sensitive)."

Enrollment open • Platinum resistant • Platinum sensitive • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer

FRAmework-01: A Two-Part Phase 3 Study of LY4170156 in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer (clinicaltrials.gov) - P3 | N=1080 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Platinum sensitive • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

LOXO-FRA-24001: A Study of LY4170156 in Participants With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=495 | Recruiting | Sponsor: Eli Lilly and Company | N=360 ➔ 495

Enrollment change • First-in-human • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • Uterine Cancer

LY4170156: Primary completion of P1 trial (NCT06400472) for ovarian neoplasms in Feb 2027 (Eli Lilly) - Q3 2025 Results: Completion of P1 trial for ovarian neoplasms in Apr 2027

Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer

Translational PK/PD modelling of LY4170156, an antibody-drug conjugate linked to exatecan via a novel cleavable polysarcosine linker (ESMO 2025) - P1 | "Preclinical and emerging clinical PK/PD data suggest a wider therapeutic index for LY4170156, supporting clinical efficacy and safety across a 2-3 fold dose range from the phase I trial in platinum-resistant ovarian cancer pts (NCT06400472). Table: 236eP Predicted human PK based on preclinical PK/PD modelling Observed PK in patients (n=21) AUC (ng*day/mL) Cmax (ng/ml) AUC (ng*day/mL) ± SD Cmax (ng/ml) ± SD Unconjugated payload 17.7 3.07 21.6 ± 14.9 3.28 ± 2.84 Conclusions Preclinical evaluation combined with translational modelling of PSAR-linked exatecan ADC provided critical data on payload release rate, half-life of LY4170156 (and its components), a projected efficacious dose and dosing regimen with human PK/PD characteristics to support the phase I design of LY4170156."

PK/PD data • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Results from the first-in-human phase I study of LY4170156, an antibody drug conjugate (ADC) targeting folate receptor alpha in recurrent platinum resistant high-grade serous ovarian cancer (HGSOC) (ESMO 2025) - P1 | "LY4170156 demonstrated preclinical in vivo efficacy across all FRα expression levels and mirvetuximab soravtansine-gynx (mirv) resistant ovarian models, as well as across multiple tumor types. Conclusions LY4170156 was well-tolerated among PROC pts with promising clinical activity across all FRα expression levels and regardless of prior mirv treatment. Updated results from the PROC dose optimization cohort (n=61) and efficacy among all FRα expression levels will be presented."

First-in-human • P1 data • Platinum resistant • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

FRAmework-01: A Two-Part Phase 3 Study of LY4170156 in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Part B) Ovarian Cancer (clinicaltrials.gov) - P3 | N=1080 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Platinum resistant • Platinum sensitive • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Solid Tumor

LY4170156 (investigational ADC targeting FRα) (PRNewswire) - "In a poster presentation, Lilly will share updated safety and efficacy results from the Phase 1a/1b study of LY4170156 in patients with platinum-resistant ovarian cancer."

P1 data • Platinum resistant • Ovarian Cancer

Initial results from a first-in-human phase 1 study of LY4170156, an ADC targeting folate receptor alpha (FRα), in advanced ovarian cancer and other solid tumors. (ASCO 2025) - P1 | "Pts with prior ADCs targeting FRα with payloads other than topo-I (including mirvetuximab soravtansine-gynx [mirv]) were allowed... LY4170156 was well-tolerated with encouraging clinical activity among HGSOC pts, including those with FRα expression < 75% and those with prior mirv. Randomized dose optimization is ongoing and updated data will be presented."

Metastases • P1 data • Anemia • Fatigue • Febrile Neutropenia • High Grade Serous Ovarian Cancer • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Lilly presents first clinical data for its investigational, next-generation FRα targeting ADC in platinum-resistant ovarian cancer at the 2025 ASCO Annual Meeting (Eli Lilly Press Release) - P1a/1b | N=360 | NCT06400472 | Sponsor: Eli Lilly and Company | "Eli Lilly and Company...announced new Phase 1 data showing that its folate receptor alpha (FRα) antibody-drug conjugate (ADC) (LY4170156) demonstrated an encouraging safety profile and anti-tumor activity across dose and FRα expression levels in women with heavily pre-treated platinum-resistant ovarian cancer, including patients previously treated with mirvetuximab soravtansine. A preliminary overall objective response rate (ORR) of 55% was observed at the potential recommended Phase 2 dose of 4 mg/kg...These data will be presented today in a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting...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)....At the potential recommended Phase 2 dose of 4 mg/kg, the ORR was 55% (11/20 patients)."

P1 data • Platinum resistant • Ovarian Cancer

Lilly announces details of presentations at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "Presentation Highlights:...(i) LY4170156 (investigational ADC targeting FRα): In a poster presentation, Lilly will report initial results from the multicenter, open-label, first-in-human Phase 1a/1b study of LY4170156 in patients with platinum-resistant ovarian cancer (PROC). LY4170156 is an Fc-silent, FRα specific humanized monoclonal antibody linked to exatecan, a topoisomerase I inhibitor, via a proprietary cleavable polysarcosine linker. The submitted abstract utilized a November 27, 2024 data cut-off date, and the poster will utilize a March 9, 2025 data cut-off date."

P1 data • Platinum resistant • Ovarian Cancer

LOXO-FRA-24001: A Study of LY4170156 in Participants with Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=360 | Recruiting | Sponsor: Eli Lilly and Company | N=220 ➔ 360

Enrollment change • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • Uterine Cancer

A First-In-Human Phase 1 Study Of LY4170156, An Antibody-Drug Conjugate Targeting Folate Receptor a (FRa)-Expressing Advanced Solid Tumors (Trial In Progress) (ESGO 2025) - P1 | "Mirvetuximab soravtansine-gynx, an FRα antibody-drug conjugate (ADC) with a DM4 payload, is approved for the treatment of platinum resistant ovarian cancer (PROC) with high FRα expression representing ~30% of PROC patients (pts). Key secondary objectives are to evaluate the pharmacokinetic profile and antitumor activity of LY4170156 per RECIST v1.1. The study is currently enrolling pts.Results NAConclusion NA"

Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • PROC

A first-in-human phase I study of LY4170156, an antibody-drug conjugate targeting folate receptor α (FRα)-expressing advanced solid tumors (ESMO 2024) - P1 | "Mirvetuximab soravtansine-gynx, an FRα antibody-drug conjugate (ADC) with a DM4 payload, is approved for the treatment of platinum resistant ovarian cancer (PROC) with high FRα expression representing ∼30% of PROC patients (pts). Primary objectives are to determine the RP2D and assess the safety of LY4170156. Key secondary objectives are to evaluate the pharmacokinetic profile and antitumor activity of LY4170156 per RECIST v1.1."

Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • PROC

A Study of LY4170156 in Participants With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Tumor cell • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • Uterine Cancer

A Study of LY4170156 in Participants With Selected Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=220 | Not yet recruiting | Sponsor: Eli Lilly and Company

Metastases • New P1 trial • Tumor cell • Breast Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • Uterine Cancer

MBK-103, a potent novel conjugation platform-based antibody-drug conjugate, changing therapeutic options in folate receptor alpha positive cancer patients (AACR 2023) - "The compound was also very well tolerated in cynomolgus monkeys with HNSTD at 50 mg/kg and even when administered repeatedly. High conjugation yields along with 100% homogeneity are major drivers of the successful ongoing manufacturing process with planned IND submission in Q4/2023."

Clinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FOLR1

Mablink Bioscience to Present Promising Preclinical Data for Lead ADC Candidate MBK-103 at the AACR Annual Meeting 2023 (GlobeNewswire) - "Mablink Bioscience...announced that preclinical efficacy and safety data on its lead ADC candidate, MBK-103, will be presented at the American Association for Cancer Research ('AACR') Meeting 2023 on April 17, 2023, in Orlando, Florida....The compound was also well tolerated in cynomolgus monkeys at the highest non-severely toxic dose (HNSTD) of 50 mg/kg administered repeatedly. These promising data are a significant differentiator in the ADC’s landscape."

Preclinical • Oncology • Solid Tumor

Mablink Bioscience Announces a €31 Million Series A Funding Round Led by Sofinnova Partners and Mérieux Equity Partners (Issuer Direct) - "Mablink Bioscience...announced today that it has raised a €31 million Series A funding round to advance its lead candidate to the clinic and to build a pipeline of ADCs using its proprietary platform technology....The proceeds of this financing round will enable Mablink to become a clinical-stage biotech by bringing its lead candidate, MBK-103, into clinical development for the treatment of solid tumors, notably ovarian cancer."

Financing • Oncology • Solid Tumor