Moving Past Empiric Chemotherapy in Platinum-Sensitive Ovarian Cancer

Sofetabart mipitecan (Sofe-M; LY4170156) is an investigational folate receptor alpha (FRα)–targeted antibody-drug conjugate (ADC) that pairs an Fc-silent, FRα-specific humanized antibody with the topoisomerase I inhibitor exatecan through a cleavable polysarcosine linker.¹ Data from the platinum-sensitive ovarian cancer cohort of a phase 1 study (NCT06400472) of Sofe-M plus bevacizumab (Avastin) were presented in an oral presentation at the 2026 European Society for Medical Oncology (ESMO) Annual Congress in Madrid, Spain.¹^˒²

The cohort included 33 patients platinum-sensitive ovarian cancer, 29 of whom had measurable disease and were evaluable for response; 67% had received prior PARP inhibitor therapy.¹ In an interview with Targeted Onc^TM, Chrisann Kyi, MD, assistant attending physician, Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, discussed the unmet need, key findings, safety, and the ongoing phase 3 FRAmework-01 study (NCT07213804).

Targeted Onc: Could you start by setting the stage and discuss some of the unmet needs that this study is looking to explore?

Chrisann Kyi, MD: Why did my colleagues and I feel it was important to conduct this research? Well, published data at this time suggest that [patients with] PARP inhibitor–exposed platinum-sensitive ovarian cancer have reduced responses to platinum doublet chemotherapy, and it is an unmet need. At the current time, the standard of care for platinum-sensitive ovarian cancer has, for the most part, remained largely unchanged over the last decade. And yet, patient characteristics have evolved. Now, more [homologous recombination deficiency (HRD)]–positive patients are cured up front, but those who do recur show only modest response rates to subsequent platinum-based chemotherapies after PARP inhibitor, around 41%. And then the non-HRD tumors derive minimal benefit from [PARP inhibitors] and have poorer prognosis.

What has been exciting over the last few years is that, in terms of gynecological oncology, we have moved away from empiric chemotherapies to biologic strategies like ADCs. That’s where our study comes to the forefront, where we use a nonplatinum agent, a folate receptor ADC, plus bevacizumab in the platinum-sensitive ovarian setting.

Could you highlight the top takeaways from the study?

The key results of this phase 1 study of Sofe-M plus bevacizumab in the treatment of platinum-sensitive ovarian cancer showed encouraging clinical activity, including a confirmed objective response rate of 79.3% and a disease control rate of 100% in heavily pretreated patients with platinum-sensitive ovarian cancer. Of note, the activity was observed across FRα expression levels, regardless of prior PARP inhibitor exposure.

At the time of data cutoff, the median duration of response and median progression-free survival had not been reached, at median follow-ups of 6.2 and 10.2 months, respectively. So, we’re going to see more mature data rolled out over the next few months and years. But we were very excited to see this very promising and encouraging clinical activity.

Additionally, this was a phase 1 study. One of the end points was safety and tolerability, and the combination was very well tolerated, with a safety profile consistent with the known profiles of each of the 2 medicines. No new safety signals were observed, with a low rate of discontinuation.

When it comes to managing the adverse events, are there any special considerations to take into account?

First and foremost, one of the most common toxicities seen with these ADCs is cytopenias. In this study, [granulocyte colony-stimulating factor (G-CSF)] was not mandated, but we did monitor with [complete blood count] checks, and it was initiated if needed. Rates of febrile neutropenia and neuropathy were low, with no high-grade neuropathy.

I think some of the toxicities that we did see as part of the combination were consistent with what we would see with bevacizumab. For example, epistaxis and stomatitis were seen, and with that sort of toxicity, they were managed with supportive meds, rinses, as well as other supportive, conservative measures, and they became manageable.

What do you see as the next steps in this line of research? What unanswered questions you still personally have?

Right now, this is being supported by further evaluation in the ongoing FRAmework-01 phase 3 study, which is looking at both platinum-resistant ovarian cancer as well as platinum-sensitive disease in the PARP inhibitor–exposed as well as naive patients. I do look forward to further information as that is understood in the phase 3.

The phase 3 FRAmework study began enrollment in quarter 4 of 2025, and it’s really 3 unique patient populations, regardless of FRα expression: platinum-resistant ovarian cancer; platinum-sensitive with progression on or within 6 months after completing a PARP inhibitor; and the platinum-sensitive, PARP inhibitor–naive group. A lot of the additional questions that we have about clinical activity in this new and unique patient population, I believe we will have further understanding, because, again, it is an unmet need at this time. The landscape of ovarian cancer is changing in our clinic, with more patients exposed to PARP inhibitors with decreasing responses to the platinum-based chemotherapies, and we are trying to find ways of shifting away from the empiric chemotherapies to more biologic strategies like ADCs, immunomodulations, and other biomarkers, and sequence-driven care.

I’m excited to have such a positive response. Really, it’s about finding new and novel strategies to treat our patients in this evolving landscape of [patients with] ovarian cancer.

REFERENCES

1. Lilly presents first clinical data in platinum-sensitive ovarian cancer for its investigational, next-generation, FRα-targeting ADC at ESMO 2026. News release. Eli Lilly and Company. October 24, 2026. Accessed November 4, 2026. https://tinyurl.com/yeyevud8

2. A study of Sofe-M in participants with selected advanced solid tumors. ClinicalTrials.gov. Updated November 4, 2026. Accessed November 4, 2026. https://clinicaltrials.gov/study/NCT06400472