A Phase 2, Open-Label, Randomized, Master Protocol Dose Optimization Study to Evaluate Safety and Efficacy of Multiple Treatment Combinations with Mirvetuximab Soravtansine in Subjects with Ovarian Cancer (FLORENZA)

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of mirvetuximab soravtansine (MIRV) in combination regimens in participants with folate receptor alpha (FRα) positive ovarian cancer, and to optimize the MIRV dose in combination regimens to determine the recommended Phase 3 dose (RP3D) in applicable substudies. These objectives are clinically relevant for establishing the therapeutic profile and optimal dosing strategy of MIRV-based combination therapies in FRα positive ovarian cancer, which may inform future Phase 3 trial design and treatment protocols.

The secondary objective is to evaluate the pharmacokinetics (PK) and immunogenicity of MIRV in combination regimens in FRα positive ovarian cancer participants. This assessment is important for understanding the drug exposure, elimination characteristics, and potential immune responses that may impact treatment efficacy and safety in the combination setting.

This clinical trial enrolled a total of **199 participants** diagnosed with **ovarian cancer**, specifically **high-grade serous ovarian cancer**, **primary peritoneal cancer**, or **fallopian tube cancer**. The study population consisted exclusively of **female participants** across adult and elderly age groups. Participants were required to have an **Eastern Cooperative Oncology Group performance status** of 0 or 1, indicating good functional capacity. The trial was divided into substudies with distinct selection criteria: Substudy 1 included participants with **FIGO Stage III or IV** disease whose tumors were confirmed as **homologous recombination deficiency test negative** (homologous recombination proficient) by local testing. Substudy 2 enrolled participants with **relapsed disease** following 1 or 2 prior lines of **platinum-based chemotherapy**, with **platinum-sensitive disease** defined as radiographic progression occurring more than 6 months after the last platinum dose. Participants in Substudy 2 were also required to have **measurable disease** according to RECIST version 1.1 criteria at baseline. All participants had tumors positive for **folate receptor alpha**. No vulnerable populations were included in this trial.

This is a **Phase 2**, **open-label**, **randomized**, master protocol study designed to evaluate the safety, tolerability, and efficacy of multiple treatment combinations with **mirvetuximab soravtansine** in participants with **ovarian cancer**. The study consists of multiple substudies, each investigating different combination regimens in specific patient populations with **folate receptor alpha** positive disease. The primary objectives are to assess the safety and efficacy of mirvetuximab soravtansine in combination regimens and to optimize the dose to determine the recommended Phase 3 dose in applicable substudies. The investigational medicinal products include **mirvetuximab soravtansine** (administered as a **concentrate for solution for infusion** via **intravenous** route), **carboplatin** (solution for injection, intravenous route), and **bevacizumab** (concentrate for solution for infusion, intravenous route). The maximum treatment periods are 88 weeks for mirvetuximab soravtansine, 24 weeks for carboplatin, and 48 weeks for bevacizumab.

The study population varies across substudies. Substudy 1 enrolls participants with FIGO Stage III or IV **high-grade serous ovarian cancer**, **primary peritoneal cancer**, or **fallopian tube cancer** who have **homologous recombination proficient** disease (HRD test negative). Substudy 2 includes participants with high-grade serous ovarian, primary peritoneal, or fallopian tube cancer who have experienced relapse after 1 or 2 prior lines of **platinum-based chemotherapy** and have **platinum-sensitive disease** defined as radiographic progression greater than 6 months from the last dose of platinum-based chemotherapy. All participants must have an **Eastern Cooperative Oncology Group performance status** of 0 or 1. Substudy 2 participants must have measurable disease per **RECIST v1.1** at baseline as assessed by the investigator.

The primary endpoints include the number of participants with **treatment-emergent adverse events** (any grade and Grade ≥ 3), the number of participants with treatment-emergent adverse events leading to discontinuation, the number of participants with **ocular adverse events** (any grade and Grade ≥ 2), and **overall response** as assessed by the investigator per RECIST v1.1. For Substudy 1, **progression-free survival** as assessed by the investigator per RECIST v1.1 is also a primary endpoint. Secondary endpoints include **CA-125 response** per **Gynecologic Cancer Intergroup** criteria, **duration of response** as assessed by the investigator per RECIST v1.1, the number of participants with **peripheral neuropathy** adverse events (any grade and Grade ≥ 2), the number of participants with **pneumonitis** or **interstitial lung disease** (any grade), and progression-free survival for Substudy 2.

The estimated recruitment start date is January 28, 2026, with an estimated study completion date of January 18, 2029, resulting in an overall trial duration of approximately 3 years. Participant involvement will vary depending on treatment response, tolerability, and disease progression. Conditions that may lead to early termination from the study include unacceptable toxicity, disease progression, participant withdrawal of consent, or investigator decision based on safety concerns.

The experimental medication **Mirvetuximab Soravtansine** (sponsor product code IMGN853) is administered as a **concentrate for solution for infusion**. The active substance, mirvetuximab soravtansine, is a protein-based therapeutic agent. The medication is administered via the **intravenous route**. The maximum treatment period for this investigational product is 88 weeks. The dosage and frequency of administration are subject to optimization during the study to determine the recommended Phase 3 dose in applicable substudies.

**Bevacizumab** is utilized in this clinical trial as part of the combination treatment regimen. The product is supplied as a **concentrate for solution for infusion** containing bevacizumab as the active substance. Administration is performed via the **intravenous route**. The maximum treatment period for bevacizumab in this study is 48 weeks. Specific dosing amounts and frequency are determined according to the study protocol for the combination regimen being evaluated.

**Carboplatin** is employed as a non-experimental comparator treatment in the study. The pharmaceutical form is a **solution for injection** containing carboplatin as the active substance, which is of chemical origin. The route of administration is **intravenous**. The maximum treatment period for carboplatin is 24 weeks. The dosing regimen follows established clinical practice for combination therapy in the treatment of **ovarian cancer**.

Efficacy will be assessed through multiple parameters in this clinical trial. The primary efficacy endpoints include the Overall Response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for both substudies, and Progression Free Survival as assessed by the investigator per RECIST v1.1 specifically for Substudy 1. Secondary efficacy endpoints comprise CA-125 response per Gynecologic Cancer Intergroup (GCIG) Criteria, Duration of Response as assessed by the investigator per RECIST v1.1 for both substudies, and Progression Free Survival as assessed by the investigator per RECIST v1.1 for Substudy 2. The trial will evaluate the efficacy of mirvetuximab soravtansine in combination regimens in participants with FRα positive ovarian cancer, with the aim of optimizing the dose to determine the recommended Phase 3 dose in applicable substudies. Participants in Substudy 2 must have measurable disease per RECIST v1.1 assessed by the investigator at baseline.