Mirvetuximab Soravtansine-Avastin Combo Linked to Promising Responses

Mirvetuximab Soravtansine-Avastin Combo Linked to Promising Responses
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When given alongside Avastin (bevacizumab), mirvetuximab soravtansine leads to promising treatment responses in women with recurrent ovarian cancer — particularly those whose tumors contain high levels of the protein folate receptor alpha (FRα), top-line data from a Phase 1b/2 trial shows.

The trial findings were presented in “Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-agnostic ovarian cancer,” an oral presentation given recently at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) currently being developed by ImmunoGen for the treatment of ovarian cancer and other types of solid tumors.

It is made up of an antibody that specifically binds to FRα, a protein found in high levels in most types of ovarian cancer. When the antibody binds to its target, it releases a toxic compound, called maytansinoid DM4, that kills cancer cells without harming healthy cells.

The FORWARD II Phase 1b/2 trial (NCT02606305) is currently assessing the safety, tolerability, and anti-tumor activity of different mirvetuximab soravtansine combo regimens — including combinations with Avastin, Keytruda (pembrolizumab), or chemotherapy — in women with FRα-positive recurrent ovarian, peritoneal, or fallopian tube cancers.

A triple combination therapy of mirvetuximab soravtansine, carboplatin, and Avastin also is being tested in women with FRα-positive, platinum-sensitive ovarian cancer. These patients initially responded to treatment and did not relapse in the first six months after receiving platinum-based chemotherapy.

Top-line findings from FORWARD II, presented at the ASCO meeting, included data from 60 women with FRα-positive recurrent ovarian cancer who were treated with a combination of mirvetuximab soravtansine and Avastin.

The participants included in this analysis had a median age of 60, and had previously received one to four lines of therapy. More than half (53%) had platinum-resistant ovarian cancer, meaning they relapsed within six months of receiving platinum-based chemotherapy. The rest of the women (47% ) had platinum-sensitive disease.

In the overall trial population, nearly half (47%) of the participants responded to the combination therapy.

This percentage was even higher among women with high levels of FRα in their tumors (64%). There was a 59% response among those with platinum-resistant disease and a 69% response for participants with platinum-sensitive disease.

“The data presented at ASCO demonstrate the potential of mirvetuximab to serve as the combination agent of choice for both platinum-sensitive and platinum-resistant recurrent ovarian cancer,” Anna Berkenblit, MD, senior vice president and chief medical officer of ImmunoGen, said in a press release.

Study author Lucy Gilbert, MD, professor at McGill University Health Center in Montreal, Canada, said well-tolerated therapies are still needed for women with recurrent disease regardless of platinum status.

“With this combination, the overall response rate in the platinum-resistant subset is more than twice the usual response rate for this population and similarly, in the platinum-sensitive subset, the overall response rate is higher than previously seen with platinum-based doublets,” Gilbert said.

At a median follow-up of 8.5 months, with nearly half of the patients with high levels of FRα still involved in the study, it is still early to tell how long treatment responses will last and how long patients will live without showing signs of disease progression.

Most adverse events observed during the study were manageable and consistent with the safety profile of both medications when given alone.

The most common treatment-related adverse events reported during the trial included diarrhea, blurred vision, fatigue, and nausea. Serious adverse events were rare, with the most frequent being small bowel obstruction and pneumonitis.

“These promising results confirm previously reported mirvetuximab plus bevacizumab data demonstrating a deeper and more durable tumor burden reduction in women whose tumors express high levels of FRα,” said David O’Malley, MD, professor and director of the division of gynecology oncology at OSUCCC – James, and principal investigator of FORWARD-II.

“These results add to the body of evidence that mirvetuximab can potentially be used to treat a broader patient population. I look forward to further evaluating these data as they mature,” O’Malley said.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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