At the ESMO 2024 conference, FRα (Folate Receptor Alpha)-targeting antibody-drug conjugates (ADCs) are making headlines as groundbreaking treatments for cancers that overexpress this receptor, particularly ovarian cancer and endometrial cancer. These ADCs are designed to deliver potent cytotoxic agents directly to tumor cells that express FRα, offering a novel approach compared to traditional treatments. 

The established player in the FRα-ADC landscape is ELAHERE (mirvetuximab soravtansine), developed by ImmunoGen. The drug has already gained approval for platinum-resistant ovarian cancer, demonstrating significant efficacy in a difficult-to-treat patient population. The drug was first granted FDA accelerated approval in November 2022 and the conversion to full approval is based on data from the confirmatory Phase III MIRASOL trial.  ImmunoGen presents updated overall survival results of mirvetuximab soravtansine from this Phase III MIRASOL trial at the ESMO 2024, which are expected to reinforce ELAHERE’s position as a leading therapy in this field, potentially leading to expanded indications or refined dosing strategies. Other companies such as Sutro Biopharma and ProfoundBio are also set to present results from their respective FRα-ADCs, Luveltamab tazevibulin, and Rinatabart Sesutecan, respectively, at the upcoming conference. 

The emergence of FRα-ADCs comes at a time when both HER2-ADC and TROP2-targeting ADC space is moving at fast pace to establish a strong presence. TRODELVY has set a high standard in the TROP2-ADC space, showing robust results and influencing the development of subsequent TROP2-targeting therapies, whereas ENHERTU’s recent tumor agnostic label in all HER2+ Solid tumors is expected to drive stronger sales.

Unveiling the latest in FRα-targeting ADC space

• Abstract Number – 718MO
• Abstract Type – Mini oral session 
• Indication - Platinum-Sensitive Ovarian Cancer (PSOC)
• Target- FRα

Title:  ELAHERE Shows Promise in Platinum-Sensitive Ovarian Cancer: Key Insights from the Phase II PICCOLO Trial at ESMO 2024

Executive Summary: ELAHERE approved for platinum-resistant ovarian cancer, is showing promising results in the Phase II PICCOLO trial for recurrent platinum-sensitive cases, with a notable 51.9% objective response rate. 

Main Content –  

Ovarian cancer is the leading cause of death among gynecological cancers in the United States. Platinum-based chemotherapy remains the most active treatment for earlier lines of ovarian cancer.  Significant unmet needs remain for patients with platinum-sensitive disease, as each subsequent line of therapy in this setting is associated with decreased efficacy and tolerability, which reinforces the need for treatment alternatives for these patients. 

ELAHERE, a first-in-class ADC comprising a folate receptor alpha-binding antibody has already received full approval in platinum-resistant ovarian cancer setting in March 2024, following its original accelerated nod in November of 2022. The company is now evaluating the drug in a Phase II PICCOLO trial for the treatment of recurrent platinum-sensitive ovarian cancer. 

Recently, in June 2024, AbbVie announced that ELAHERE met its primary endpoint in the midstage PICCOLO trial, triggering an objective response rate of 51.9%. The mid-stage trial win comes after AbbVie's USD 10.1 billion buyout of ImmunoGen. Part of the strategy behind the deal is to move ELAHERE into earlier lines of treatment. With its recent play for ImmunoGen, AbbVie has rejoined a suite of Big Pharma players embracing the ADC field, including AstraZeneca, BioNTech, Gilead Sciences, Merck, and Pfizer. AbbVie also plans to explore adding ELAHERE to either Roche’s AVASTIN or PARP inhibitors in the first-line maintenance setting. The company has planned to reveal detailed results from the PICCOLO trial at the ESMO 2024. As the competitive landscape continues to evolve, ELAHAERE’s unique mechanism and positive trial outcomes could redefine treatment strategies and enhance outcomes for this challenging patient population.

• Abstract Number – 719MO
• Abstract Type – Mini oral session 
• Indication - Advanced Ovarian cancer or Advanced Endometrial Cancer
• Target- FRα

Title: Can Profound/Genmab’s FRα-ADC’s Early Success, could turn out to be the next big breakthrough for advanced ovarian and endometrial cancers? 

Executive Summary: Rinatabart Sesutecan (Rina-S), a novel ADC recently acquired by Genmab, demonstrated promising early results in advanced ovarian and endometrial cancers with detailed findings set to be presented at the ESMO 2024 conference.

Main Content –  

Rinatabart Sesutecan, originally developed by ProfoundBio, was acquired by Genmab in May 2024, for USD 1.8 billion. Genmab sees an opportunity to establish Rina-S as a major drug, reflecting its belief that the molecule is a potential best-in-class asset. Buying ProfoundBio, also gives Genmab control of a clutch of other candidates that ProfoundBio is developing such as ADCs that target CD70 and PTK7 plus a bispecific ADC that hits EGFR and cMET.

Rina-S's potential advantage lies in its targeted delivery of cytotoxic agents directly to tumor cells, which could result in improved efficacy and reduced systemic toxicity compared to traditional chemotherapy. In the study, Rina-S demonstrated promising early results. The drug achieved a notable objective response rate (ORR) in both ovarian and endometrial cancer cohorts, with some patients experiencing partial responses and disease stabilization. These findings suggest that Rina-S could provide a new option for patients with limited treatment alternatives, especially those who have failed conventional therapies. The company is geared up to present the findings at ESMO 2024 conference as a mini oral session, representing a new approach to targeting these challenging cancers, offering potential improvements over current therapies.

Top Abstracts summarizing FRα targeting ADCs