ESMO26: Lily's sofe-m ADC stakes a claim in ovarian cancer

Eli Lilly's first major readout at ESMO comes from a phase 1 trial of its folate receptor alpha (FRα) antibody-drug conjugate, sofetabart mipitecan (sofe-m), in platinum-sensitive ovarian cancer (PSOC).

The 33-patient study enrolled 33 patients with PSOC whose disease had progressed despite prior platinum-based chemotherapy and who were treated with a combination of sofe-m and the anti-VEGF antibody bevacizumab.

Sofe-m achieved an impressive 79.3% confirmed objective response rate (cORR) in the study, including a 20.7% complete response rate and a disease control rate (DCR) of 100%. The ADC's activity was consistent regardless of prior exposure to PARP inhibitors, a standard therapy for this type of cancer.

In addition, around 10% of the subjects had previously been treated with AbbVie's first-to-market FRα-targeting ADC, Elahere (mirvetuximab soravtansine), which has been approved for platinum-resistant ovarian cancer (PROC) but achieved mixed results in PSOC in the phase 2 MIROVA trial. Sales of the drug were $690 million last year

From a safety perspective, the most common serious treatment-emergent adverse events (TEAEs) were neutropenia and anaemia, affecting 42% and 24% of patients, respectively, while the most common side effects overall were nosebleeds and nausea. Dose reductions were needed in 42% of patients and 6% discontinued treatment altogether.

Sofe-m was acquired by Lilly as part of its 2023 takeover of French biotech Mablink Bioscience and its PSARLink ADC development platform, which is designed to mask the cytotoxic payload carried by the drug molecules, reducing the chances that it will be released early and cause off-target side effects.

"The standard of care for platinum-sensitive ovarian cancer has remained unchanged for a decade and demands new treatment options," said Jacob Van Naarden, president of Lilly Oncology, in a statement.

"Results for sofe-m show a promising efficacy and tolerability profile across both platinum-resistant and platinum-sensitive ovarian cancer, regardless of FRα expression levels or prior treatment," he added.

Sofe-m is currently being studied in both PSOC and PROC in Lilly's phase 3 FRAmework-01 programme, which includes three studies. Part A is testing the ADC as a monotherapy in PROC, while Part B and Part C are evaluating sofe-m plus bevacizumab in PARP-exposed and PARP-naive PSOC, respectively.

Van Naarden said the phase 1 results "give us confidence as we continue to study sofe-m in our phase 3 FRAmework-01 programme to bring this potential new medicine to the women who need it."