Dr. Elizabeth K. Lee 

Breaking Down The Use of Rina-S in Advanced Ovarian Cancer

Rinatabart sesutecan (Rina-S) is an antibody-drug conjugate that targets folate receptor-alpha (FRα) and delivers a TOP1 inhibitor directly to cancer cells, according to a press release, which went on to note that in the phase 2 RAINFOL-01 clinical trial, Rina-S demonstrated antitumor activity in patients with advanced ovarian cancer who had received multiple prior treatments.

Updated findings from RAINFOL-01 showed that patients treated with Rina-S at a dose of 120 milligrams per square meter experienced a confirmed objective response rate of 55.6%. The median duration of response had not yet been reached at the time of analysis. These results were observed regardless of the level of FRα expression on the tumor cells.

Notably, FRα is a protein commonly found on the surface of cancer cells, according to the National Institutes of Health, and is produced by the FOLR1 gene, serving as a useful target for therapies that aim to attack cancer cells.

In an interview with CURE, Dr. Elizabeth K. Lee, a medical oncologist and physician in the gynecologic oncology program at Dana-Farber Cancer Institute, in Boston, dives into the data and what this means for patients.

Lee also serves as the gynecologic oncology program's liaison to the Center for Cancer Therapeutics Innovation at Dana-Farber Cancer Institute, and is also an instructor in medicine at Harvard Medical School.

We are all very encouraged by the preliminary activity of Rina-S within the dose expansion cohort of ovarian cancer patients in RAINFALL-01 — I know there are many different names and trial numbers. This preliminary activity has led to Part C of RAINFALL-01, which is a roughly 100-patient dose expansion specifically in patients with platinum-resistant ovarian cancer.

It's important to note that if a patient has a folate receptor alpha expression level that meets the criteria for receiving Elahere [mirvetuximab soravtansine], they are required to have received it. I think this also touches on a recurring question in the antibody-drug conjugate space regarding the sequencing of different antibody-drug conjugates.

[Looking] back to 2024 [conference data], we noted a handful of patients who had received Elahere and had had target lesion reductions and responses with Rina-S. Certainly, having many more patients, hopefully around 100 patients in Part C of RAINFALL-01, with hopefully many more having received Elahere, will help bolster that data. Then, we'll get a better idea of the activity of Rina-S even in the post-Elahere setting.

Part C of RAINFALL-01 is currently enrolling and is active at multiple sites, although it is not yet fully enrolled. The data from Part B1 has also informed the randomized phase three trial that you just mentioned. This randomized phase three trial will study Rina-S at a dose of 120 milligrams per meter squared compared to investigator's choice chemotherapy. It will be a 1:1 randomization, with patients assigned to one treatment arm or the other. This will be a fairly large study, and hopefully, we will get the clearest sense of the activity of Rina-S from it.

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Videos

Dr. Elizabeth K. Lee discusses the RAINFOL-01 clinical trial evaluating treatment with Rina-S in advanced ovarian cancer.

Treatment with Rina-S showed antitumor activity in heavily pretreated patients with advanced ovarian cancer, according to the phase 2 RAINFOL-01 study.

Rina-S Generates Antitumor Activity in Heavily Pretreated Ovarian Cancer

Treatment with rinatabart sesutecan (Rina-S), a folate receptor-alpha (FRα)-targeted TOP1 antibody-drug conjugate, showed antitumor activity among heavily pretreated patients with advanced ovarian cancer, according to data from the phase 2 RAINFOL-01 study.

Updated results from RAINFOL-01 showed that heavily pretreated patients with advanced ovarian cancer who were treated with Rina-S at 120 milligrams per square meter achieved a confirmed objective response rate of 55.6%, with median duration of response not yet reached, regardless of folate receptor alpha (FRα) expression levels. FRα, according to the National Institute of Health, is a protein found on many cancer cells, making it a target for cancer treatment. It is produced by the FOLR1 gene and can help develop therapies that specifically attack cancer while sparing healthy cells.

To delve deeper in the importance of targeting FRα, and the difference targeted therapies can make in cancer treatment, Dr. Elizabeth K. Lee sat down for an interview with CURE. In the interview, she delved into detail on the RAINFOL-01 clinical trial and expanded on FRα testing.

Lee is a medical oncologist and physician in the gynecologic oncology program at Dana-Farber Cancer Institute, in Boston, and she serves as the gynecologic oncology program's liaison to the Center for Cancer Therapeutics Innovation. She is also an instructor in medicine at Harvard Medical School.

Testing for FRα is now part of our standard of care testing, and really that should be considered. [I do this] in my clinical practice for anyone with a recurrence; I also tend to do this for some with advanced disease at the [time of] diagnosis because of the increased likelihood of a disease recurrence. The FDA approved drug right now is Elahere [mirvetuximab], and so that has a companion diagnostic assay that any medical oncology provider can order for their patient with ovarian cancer to get that information. Where Elahere is approved is for those patients who have expression levels of 75% at a score of PS2 plus or greater, so that's where they can get that information: Do they qualify for Elahere if they meet that threshold, or do they not?

It is important to understand the landscape as well, [especially with] the phase 2 data of the combination of Elahere and Avastin [bevacizumab]. That combination is within our National Comprehensive Cancer Network guidelines for patients who have expression levels that don't meet that 75% cut off. I think that's also just a weird, little [nuanced] part related to the current FRα approved [therapy].

Having that information is important because it also means that you can potentially consider trials like RAINFOL-01 for patients with ovarian cancer who may have already received Elahere and subsequently progressed, or who cannot access Elahere and Avastin as a combination. Because it is still phase 2 data, it is not currently under an FDA label, even though it is within National Comprehensive Cancer Network guidelines. Sometimes there may be some insurance issues because it's not technically on a label, and so [patient’s] may not be able to access Elahere.

Knowing that FRα testing, which is available [as a] diagnostic, can open up clinical trial options.

Dr. Elizabeth K. Lee

Breaking Down The Use of Rina-S in Advanced Ovarian Cancer

Rina-S Generates Antitumor Activity in Heavily Pretreated Ovarian Cancer

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