Phase 3 Study of LY4170156 (Sofetabart Mipitecan) ± Bevacizumab versus standard chemotherapy in platinum‑resistant and platinum‑sensitive ovarian cancer

Primary objective: In the platinum‑resistant ovarian cancer cohort (Part A), to compare the efficacy of sofetabart mipitecan with the control arm (investigator’s choice of chemotherapy or mirvetuximab soravtansine). In the platinum‑sensitive ovarian cancer cohort (Part B), to compare the efficacy of sofetabart mipitecan plus bevacizumab with investigator’s choice of platinum‑based doublet chemotherapy plus bevacizumab. These objectives aim to determine whether the investigational regimens provide superior clinical benefit in populations stratified by platinum response status.

The trial enrolled 639 female patients with histologically confirmed ovarian cancer or related fallopian tube or peritoneal neoplasms. Participants were required to have adequate organ function and blood counts and to be ambulatory enough to perform light work. The population comprised individuals whose disease had either recurred within six months of the last platinum‑based therapy (platinum‑resistant cohort) or recurred after six months (platinum‑sensitive cohort). Selection was based on confirmed diagnosis of ovarian, fallopian tube, or peritoneal carcinoma, meeting laboratory criteria for organ function, and ability to tolerate study treatment. No specific dietary or exercise regimens were mandated, although functional status implying regular light activity was a prerequisite. Key inclusion elements included documented disease recurrence timing relative to prior platinum therapy and overall health sufficient for study participation.

The FRAmework-01 study is a Phase 3 controlled trial evaluating Sofetabart Mipitecan (LY4170156) versus investigator‑chosen chemotherapy or mirvetuximab soravtansine in platinum‑resistant disease (Part A) and Sofetabart Mipitecan plus bevacizumab versus platinum‑based doublet chemotherapy plus bevacizumab in platinum‑sensitive disease (Part B). Eligible participants must have ovarian, fallopian‑tube, or peritoneal carcinoma, adequate organ function, and meet the respective platinum‑free interval criteria (≤6 months for Part A, ≥6 months for Part B). After a screening visit to confirm eligibility, a baseline visit (Day 0) is performed before study treatment is administered intravenously according to the assigned arm. Treatment cycles are given every 21 days, with safety assessments, laboratory tests, and imaging at each cycle. Follow‑up visits occur every 8 weeks for tumor assessment and continue until disease progression, unacceptable toxicity, withdrawal, or the end‑of‑study visit at study closure. The primary efficacy endpoint is Progression‑free Survival assessed per RECIST v1.1 (investigator‑reported in Part A and blinded independent central review in Part B). Participants remain in the trial for the duration of treatment and subsequent follow‑up, which may extend several months beyond the last dose. Early termination may be triggered by disease progression, treatment‑related adverse events meeting stopping criteria, patient withdrawal of consent, or death. The overall recruitment period spans from March 2026 to August 2031.

Sofetabart Mipitecan (LY4170156) is supplied as a lyophilized powder for solution for injection. The investigational product is administered by intravenous infusion in accordance with the protocol‑defined dose and schedule, typically on the first day of each treatment cycle. Administration is performed under controlled conditions and documented in the infusion record.

mirvetuximab soravtansine is provided in the pharmaceutical form PHF00230MIG and contains the active substance mirvetuximab soravtansine. The drug is given as an intravenous infusion at a dose of 6 mg/kg body weight. Dosing follows the protocol schedule, and each infusion is recorded to ensure adherence.

bevacizumab is supplied as PHF00230MIG for intravenous use. The antibody is administered by intravenous infusion at a dose of 15 mg/kg. Infusions are performed on the designated treatment days and logged for compliance monitoring.

PACLITAXEL is formulated as PHF00230MIG for intravenous use. The chemotherapeutic agent is infused at a dose of 175 mg/m². Each administration is documented in the patient’s treatment log.

CARBOPLATIN, also supplied as PHF00230MIG for intravenous use, is administered at a dose of 900 mg/m². Infusion details are captured in the study records to track dosing compliance.

GEMCITABINE HYDROCHLORIDE is provided in the form PHF00230MIG for intravenous administration at a dose of 1,000 mg/m². Dosing events are recorded in the trial database.

TOPOTECAN is supplied as PHF00006MIG for intravenous infusion at a dose of 4 mg/m². Each infusion is entered into the study’s compliance monitoring system.

DOXORUBICIN HYDROCHLORIDE, formulated as PHF00231MIG for intravenous use, is given at a dose of 40 mg/m². Administration details are captured to ensure protocol adherence.

The control arm may consist of the investigator’s choice of one of the listed chemotherapeutic agents or mirvetuximab soravtansine, administered according to standard dosing regimens. All study medications are delivered by intravenous infusion, and dosing compliance is monitored through infusion logs, electronic case report forms, and periodic source‑document verification.

The efficacy assessment relies on the primary endpoint of Progression-free Survival. In Part A, PFS is measured according to RECIST v1.1 by the investigator, while in Part B, PFS is evaluated by blinded, independent central review using the same RECIST criteria.