FRAmework-01: A two-part phase 3 study of sofetabart mipitecan versus chemotherapy or mirvetuximab soravtansine in platinum-resistant ovarian cancer (PROC), and sofetabart mipitecan plus bevacizumab versus platinum-based chemotherapy plus bevacizumab in platinum-sensitive ovarian cancer (PSOC).

TPS5644 Background: Folate receptor alpha (FRα) is overexpressed in ovarian cancer and is a validated therapeutic target. Mirvetuximab soravtansine (MIRV), an antibody drug conjugate (ADC) targeting FRα, is approved for the treatment of patients with PROC and high FRα expression (≥75% tumor cells with 2+ and/or 3+ staining intensity). Given MIRV’s limited indication and its association with specific side effects, including ocular adverse events and peripheral neuropathy, there remains a significant medical need to improve outcomes for a broader population of patients with ovarian cancer. Sofetabart mipitecan is an FRα-targeting ADC composed of an Fc-silenced, humanized IgG1 antibody, a novel polysarcosine hydrophobicity masking agent with a dipeptide cleavable linker, and the topoisomerase I inhibitor payload exatecan at a drug-antibody ratio of 8. Data from the Phase 1 study indicate that sofetabart mipitecan monotherapy demonstrates promising and durable clinical activity, with high objective response rates and a tolerable safety profile, in heavily pretreated patients with PROC. Responses were observed across all FRα levels, including in patients who received prior MIRV treatment, and there were no reports of keratopathy or significant peripheral neuropathies. Sofetabart mipitecan was recently granted Breakthrough Therapy Designation by the FDA. Methods: In Part A, 530 participants with PROC who received ≤3 prior lines of systemic cytotoxic therapy (or ≤4 lines if MIRV was included), will be randomized in a 1:1 ratio to receive either sofetabart mipitecan, or the investigator’s choice (IC) of chemotherapy (paclitaxel, pegylated liposomal doxorubicin [PLD], gemcitabine, or topotecan) or MIRV (if eligible per local label). In Part B, 550 participants with PSOC who received ≤2 prior lines of systemic cytotoxic therapy and had disease progression either during or within six months of completing treatment with a poly (ADP‐ribose) polymerase inhibitor (PARPi), will be randomized in a 1:1 ratio to receive either sofetabart mipitecan plus bevacizumab (bev), or the IC of carboplatin-based chemotherapy (paclitaxel, PLD, or gemcitabine) plus bev. Study Parts A and B will enroll participants irrespective of their tumor’s FRα expression level. Each part has progression-free survival as its primary endpoint, while overall survival is a key secondary endpoint. Study parts will be conducted separately, and statistical analyses will be performed independently. Trial Status: The study is actively enrolling participants in Part A and B. Clinical trial information: NCT07213804 .