New ADCs and immuno-oncology drugs approved for ovarian cancer

Keytruda receives FDA Approval for PD-L1 positive platinum-resistant ovarian cancer

Lilly develops FRα-targeted ADC following Elahere…shows potential in clinical trials

The treatment landscape for platinum-resistant ovarian cancer (PROC) is rapidly expanding.

Following the antibody-drug conjugate (ADC) ‘Elahere’ (mirvetuximab soravtansin), the immunotherapy ‘Keytruda’ (pembrolizumab) has gained a new indication in the US, marking its full-fledged entry into the ovarian cancer field. Eli Lilly is also focusing on developing a new ADC targeting the area.

Keytruda+paclitaxel demonstrates benefit regardless of Avastin use

Immuno-oncology drug Keytruda

According to industry sources on the 12th, the U.S. Food and Drug Administration (FDA) recently approved Keytruda in combination with ‘paclitaxel ± Avastin (bevacizumab)’ for patients with PD-L1 (CPS ≥1) positive platinum-resistant ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

For epithelial ovarian cancer, which accounts for 90% of ovarian cancers, taxane-based drugs like paclitaxel and platinum-based anticancer drugs like carboplatin and cisplatin are primarily used.

However, for platinum-resistant ovarian cancer, which is resistant to platinum-based drugs, response rates to standard chemotherapy have generally been low, significantly limiting survival improvements.

This approval is based on results from the Phase III KEYNOTE-B96 trial. In this trial, patients were randomized 1:1 to either Keytruda + paclitaxel (± Avastin) or placebo + paclitaxel (± Avastin).

Analysis of 466 PD-L1-positive patients showed that the PFS in the Keytruda combination group was 8.3 months, compared to 7.2 months in the placebo combination group. Overall survival (OS) was also 18.2 months in the Keytruda combination group versus 14.0 months in the placebo combination group. This is considered the first clinical trial demonstrating a clear survival benefit for immunotherapy in platinum-resistant ovarian cancer.

The safety profile was consistent with known Keytruda adverse reactions, with continued emphasis on the need for monitoring immune-mediated adverse reactions.

Alongside Keytruda’s indication approval, the FDA also approved PD-L1 IHC 22C3 pharmDx as a companion diagnostic, enabling patient selection.

Notably, consistent benefits were confirmed regardless of whether Avastin, the existing standard therapy, was included in the combination regimen. This has led to the assessment that immunotherapy-based combination strategies are emerging as a new pillar in ovarian cancer treatment.

Lilly develops next-generation FRα ADC

As the immunotherapy Keytruda received FDA approval for platinum-resistant ovarian cancer, broadening treatment options in platinum-resistant ovarian cancer, a new follow-up candidate has emerged in the field of FRα-targeted antibody-drug conjugates (ADCs) as well.

Eli Lilly’s investigational FRα ADC, sofetabart mipitecan, recently received Breakthrough Therapy designation from the FDA.

The designation specifically applies to patients previously treated with Avastin and AbbVie's already commercialized FRα ADC, Elahere. While Elahere offers later line options for patients with FRα overexpression, sofetabart mipitecan demonstrated differentiated benefit by showing responses regardless of FRα expression levels.

ADC anticancer drug ‘Elahere’

FRα, the target of both Elahere and sofetabart mipitecan, is minimally expressed in normal tissues but highly overexpressed in ovarian cancer cells.

Research indicates that approximately 35-40% of ovarian cancer patients are classified as FRα-positive, meeting Elahere’s FRα positivity criteria.

The breakthrough therapy designation of sofetabart mipitecan is based on Phase I clinical trial results (NCT06400472). Data presented at major global conferences last year reported an overall response rate (ORR) of approximately 45-50% and a disease control rate (DCR) of approximately 74-78% for sofetabart mipitecan.

Notably, the ORR rose to 55% in the 4mg/kg dose group, leading to its selection as the provisional recommended Phase II dose (RP2D). More significantly, ORRs of 40–54% were consistently observed across FRα expression subgroups.

Regarding safety, nausea, anemia, fatigue, and vomiting were the most common adverse events. Grade 3 or higher adverse reactions included anemia (20–25%) and neutropenia (18–24%). Notably, high-grade ocular toxicity and peripheral neuropathy, which were issues in previous ADCs, were not observed. Pharmacokinetically, minimal drug accumulation was confirmed, supporting a 3-week dosing interval.

The designation of this innovative therapy, which explicitly specifies the patient population, carries significant implications for future treatment sequencing. The fact that it demonstrated meaningful response even in patients who had already undergone Avastin and Elahere therapy suggests this ADC has the potential to emerge as a new standard option in later-line therapy. Lilly is currently conducting a Phase 3 clinical trial for sofetabart mipitecan.