Gynecological Cancer Highlights: ASCO 2021

DelveInisght has picked a few of the most pivotal abstracts presented at ASCO21 in Gynecological Cancer. Read on to know more. 

Abstract #5504: ImmunoGen’s Future Plan for Label Expansion of Mirvetuximab Soravtansine

The approval of anti-angiogenic agents (bevacizumab) and PARP inhibitors has changed the ovarian cancer market. These advancements in the maintenance therapy of ovarian cancer have improved the survival of patients. However, a huge unmet need persists for patients with platinum-resistant recurrent ovarian cancer. New molecular targets are now being explored to further improve the clinical outcomes in these patients. One of such novel targets is folate receptor α (FRα).

ImmunoGen is evaluating Mirvetuximab Soravtansine, an FRα-targeting antibody-drug conjugate (ADC), for the treatment of patients with 2L–4L platinum-resistant, advanced high-grade ovarian cancers with high FRα expression. The post hoc exploratory analysis of the Phase III FORWARD I trial was positive, and replication of the results in the Phase III SORAYA trial will open the door for the accelerated approval of mirvetuximab soravtansine. The US FDA guided that based on the targeted population, the success of the SORAYA trial is a 12% overall response rate (ORR). In the post hoc analysis of the FORWARD I trial, the ORR with mirvetuximab soravtansine was found to be 24%, which is almost double that suggested by the FDA. Hence, experts are very certain about its success in the SORAYA trial.

The company is planning to submit the data from the SORAYA trial to the FDA by the end of 2021 to get approval. Thereafter, will seek full approval based on the confirmatory Phase III MIRASOL trial. ImmunoGen also partnered with Roche Tissue Diagnostics for the development and commercialization of diagnostics based on the PS2 scoring method, which will be used to identify FRα high expressers. Mirvetuximab soravtansine has already received Fast Track designation and Orphan Drug designation from the US FDA and Orphan Drug designation from the European Commission.

With high hopes from the expected approval of mirvetuximab soravtansine monotherapy, the company is exploring the ADC in combinations with other agents in earlier lines of ovarian cancer treatment. ImmunoGen is mainly focusing on three combinations mirvetuximab soravtansine plus bevacizumab, mirvetuximab soravtansine plus carboplatin, and mirvetuximab soravtansine plus bevacizumab and carboplatin in recurrent ovarian cancer.

The mature data presented from the Phase I/II FORWARD II trial at ASCO 2021 revealed that mirvetuximab soravtansine with bevacizumab had achieved an overall response rate (ORR) of 50% in overall treated patients. High ORR (64%) was observed in patients with high expression of folate receptor alpha (FRα) compared to medium FRα expression (ORR 33%). It makes it a suitable combination therapy for high FRα expressing recurrent ovarian cancer with an ORR of 64%, the median duration of response (mDOR) of 11.8 months, and the median progression-free survival (mPFS) of 10.6 months. This Combination therapy has also been found to be effective in both platinum-resistant (ORR 59%) and platinum-sensitive (ORR 69%) recurrent ovarian cancer. Apart from the great response, it is also effective in reducing the tumor burden in 97% of the patients. It has shown favorable tolerability, and most of the treatment-related adverse events (AEs) were of low grade. This impressive result will help the company to establish mirvetuximab soravtansine as a combination agent of choice in high FRα recurrent ovarian cancer regardless of platinum sensitivity.

Other FRα-targeting agents evaluated in phase II and III trials in recurrent ovarian cancer are Farletuzumab, Vintafolide, and TPIV200. However, they have failed to show any clinical benefit. Some FRα-targeting therapies such as CT900 and STRO-002 are evaluated in Phase I of the clinical trial; hence it will be early to predict their future.

The failure of farletuzumab and vintafolide has shown that there is a vast opportunity for FRα-targeting ADCs. FRα can easily internalize large molecules, making them a suitable target for ADC. In addition, the benefit of ADC is antigen specificity and extended half-life. As approximately 40% of ovarian cancer patients are FRα high expressers, the combination will capture a decent market share on approval and will fulfil the unmet need of platinum-resistant recurrent ovarian cancer patients.

Experts Views: “The promising results will further support the plan of the company for compendia listing of mirvetuximab plus bevacizumab combination in the recurrent setting in 2022.

Abstract 5501_bevacizumab (BEV) combined with carboplatin and paclitaxel_ primary epithelial ovarian (EOC), fallopian tube (FTC) or peritoneal cancer_ Roche

Consistent safety but no survival benefit with prolongation of the treatment duration of bevacizumab

The Phase III AGO-OVAR 17/BOOST/GINECO OV118/ENGOT Ov-15  trial data revealed that despite a consistent safety profile over 30 months, bevacizumab does not offer survival benefit over 15 months. The prolongation of treatment duration does not improve either median PFS (26.0 months vs. 24.2 months; treatment duration 30 months vs. 15 months ) or overall survival (54.3 months vs. 60 months; treatment duration 30 months vs. 15 months ).

Experts Views: “The results show that there is no change in the previously determined 15 months duration of treatment as standard in the first-line treatment setting of advanced ovarian cancer.

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