Mirvetuximab Soravtansine Combo Therapies Show Promise for Ovarian Cancer, Clinical Trial Shows

Mirvetuximab Soravtansine Combo Therapies Show Promise for Ovarian Cancer, Clinical Trial Shows

Combinations of mirvetuximab soravtansine (IMGN853) with either Avastin (bevacizumab) or Paraplatin (carboplatin) are showing promise in certain ovarian cancer patients, particularly those who received multiple prior lines of therapy, the investigational therapy’s developer, ImmunoGen, recently announced. The data come from an ongoing Phase 1b/2 trial.

Mirvetuximab soravtansine is a potential new treatment for patients with folate receptor alpha (FRα)-positive cancer. It is an antibody-drug conjugate that targets FRα-positive cancer cells and kills them with a toxic compound known as DM4.

FORWARD II, a Phase 1b/2 study (NCT02606305), is evaluating the safety and preliminary efficacy of mirvetuximab soravtansine in combination regimens in patients with FRα-positive advanced epithelial ovarian cancer, primary peritoneal, or fallopian tube tumors.

Patients are assigned to receive mirvetuximab in combination with one of four chemotherapies: Avastin, Paraplatin, Doxil (pegylated liposomal doxorubicin), or Keytruda (pembrolizumab).

The first part of the study is a dose escalation phase that will determine the maximum tolerated dose for each combination regimen. That will be followed by an expansion study with the defined maximum dose to assess safety, tolerability, and preliminary efficiency.

ImmunoGen’s recent announcement includes the results of the Avastin combo in ovarian cancer patients and the updated results of the Paraplatin group.

The combination of mirvetuximab with Avastin was given to 59 patients with platinum-resistant ovarian cancer, and showed durable responses and a consistently manageable safety profile, according to ImmunoGen.

Among the 54 patients able to be evaluated for treatment response, 43 percent responded to treatment and lived without signs of disease progression for a median of 7.8 months. Patients had received a median of three previous lines of therapy, and Avastin was one of those therapies in more than half of the patients.

Further analysis showed that the best outcomes were found in the group of 23 patients with medium or high levels of FRα who had received up to three previous lines of therapy. Treatment responses were achieved by 48 percent of patients, with a median progression-free survival (PFS) of 9.9 months and a median duration of response of 10.6 months.

The four most commonly reported adverse events were non-severe nausea, fatigue, diarrhea, and blurred vision (45-57 percent), while hypertension was the most frequent severe adverse event reported (16 percent). The combination’s safety profile is in accordance with the profiles of each therapy, and no new adverse events were reported.

The results of the combination of mirvetuximab with Avastin will be presented on June 4 at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, in a poster titled “Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Maturing safety and activity profile from the FORWARD II phase 1b study.”

For the group of patients receiving mirvetuximab in combination with Paraplatin — of whom 50 percent had previously received three or more lines of therapy — the updated results showed that 71 percent of patients responded to treatment and lived without disease progression for a median of 15 months. In the subset of 10 patients with medium or high levels of FRα, treatment response was achieved by 80 percent of patients, with a median PFS of 15 months.

Based on the positive data of these Avastin and Paraplatin groups, ImmunoGen recently initiated a new study group in the FORWARD II trial that will evaluate a triple combination therapy of mirvetuximab, Avastin, and Paraplatin in patients with recurrent ovarian cancer who responded to prior platinum chemotherapy.

“The promising new data reported in the FORWARD II Avastin and carboplatin arms support the potential of mirvetuximab combinations in earlier lines of therapy,” Anna Berkenblit, ImmunoGen’s vice president and chief medical officer, said in a press release.

Berkenblit noted that the company plans to present initial results from the mirvetuximab-Keytruda combo later this year, and that “the totality of these data from FORWARD II will guide the next stages of development of mirvetuximab and support a path to registration for combination regimens.”