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ImmunoGen unveils promising data with mirvetuximab soravtansine in ovarian cancer

Published 18 May 2017

ImmunoGen has reported promising safety and efficacy data from monotherapy and combination trials with mirvetuximab soravtansine in patients with folate receptor alpha (FRα)-positive epithelial ovarian cancer (EOC).

These data include results from pooled analyses of three Phase 1 expansion cohorts and from a Phase 1b/2 study, FORWARD II, evaluating mirvetuximab soravtansine in combination with Avastin (bevacizumab), carboplatin, Doxil (pegylated liposomal doxorubicin), or Keytruda (pembrolizumab). These results will be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held June 2-7, 2017 in Chicago, IL.

Data from the pooled analyses demonstrate the safety and efficacy profile of mirvetuximab soravtansine in the patient population eligible for the ongoing Phase 3 registration trial, FORWARD I. These data include 113 EOC patients treated with mirvetuximab soravtansine in three expansion cohorts in the Phase 1 trial.

In the subset of 36 patients meeting the key eligibility criteria for FORWARD I, which includes patients with platinum-resistant disease and medium or high levels of FRα and who have received up to three prior lines of therapy, the confirmed overall response rate (ORR) was 47 percent (95% CI 30, 65) and median progression-free survival (mPFS) was 6.7 months (95% CI 4.1, 8.3).

Kathleen Moore, M.D., Associate Professor, Department of Obstetrics and Gynecology at the Stephenson Cancer Center at the University of Oklahoma, said: "The data observed with mirvetuximab compare favorably with outcomes typically achieved with currently available single-agent therapies for platinum resistant ovarian cancer. Current single-agent therapies for platinum-resistant ovarian cancer have low response rates of 15 to 20% and short median progression-free survival of three to four months.

"Based on the consistent safety and efficacy seen with mirvetuximab soravtansine reflected in these pooled analyses, particularly in those patients meeting the eligibility criteria for the pivotal study, I am very encouraged about the potential of this compound in patients with platinum-resistant ovarian cancer and look forward to continued progress with the ongoing Phase 3 FORWARD I trial."

For all 113 patients, the median number of prior regimens was 3, 85 percent had platinum-resistant disease, 67 percent had prior bevacizumab, and 22 percent had a prior poly (ADP-ribose) polymerase (PARP) inhibitor.

The safety profile of the pooled population was consistent with data previously reported (2016 ASCO Annual Meeting), which consisted primarily of low grade, manageable adverse events. In this heavily pretreated group of patients, the confirmed ORR was 30 percent (95% CI 22, 39) and mPFS was 4.3 months (95% CI 3.9, 5.4).

FORWARD II is a Phase 1b/2 study of mirvetuximab soravtansine in combination with Avastin, carboplatin, Doxil or Keytruda in patients with FRα-positive EOC, primary peritoneal, or fallopian tube tumors. The data from these arms demonstrate mirvetuximab soravtansine may complement currently available therapies for FRα-positive EOC in a range of treatment settings, including earlier lines of therapy.

The safety profiles for these combinations were manageable and as expected, based on known profiles of each agent, with no new safety signals identified. Key findings in over 60 patients from the dose escalation phase of FORWARD II are as follows:

Patients in the Avastin arm were heavily pretreated with a median of six prior regimens. The confirmed ORR for this arm was 29 percent (95% CI 8, 58), with a median PFS of 9.5 months (95% CI 3.5, 15.2).

Patients with recurrent platinum-sensitive disease on the carboplatin arm had received a median of three prior regimens and the confirmed ORR was 65 percent (95% CI 38, 86), with a median PFS of 12.1 months (95% CI 9.0, 15.0).

Patients on the Doxil arm received a median of two prior regimens. The confirmed ORR for the Doxil arm was 13 percent (95% CI 2, 38), with a median PFS of 7.0 months (95% CI 1.7, upper bound not estimated).

Preliminary data from the Keytruda arm demonstrate that, similar to the other combinations, full doses of each agent are combinable. At this time, it is too early to assess anti-tumor activity data in this arm; anti-tumor activity will be reported at a subsequent medical meeting.

Based on the encouraging profiles of these combinations in dose escalation, ImmunoGen is moving forward with expansion cohorts for Avastin and Keytruda and is evaluating future studies with carboplatin combinations.

"The favorable safety profile of mirvetuximab soravtansine lends itself well to combination, as evidenced by the data from FORWARD II, showing the full dose of mirvetuximab soravtansine combines with the full doses of bevacizumab (Avastin), carboplatin, pembrolizumab (Keytruda) and pegylated liposomal doxorubicin (Doxil) in ovarian cancer," stated David O'Malley, M.D., Associate Professor, Director of Gynecology Clinical Trial and Phase 1 Program, James Cancer Center and The Ohio State University Wexner Medical Center.

The Phase 3 FORWARD I trial was designed based on the promising monotherapy mirvetuximab soravtansine data from the Phase 1 trial and reflects the fastest registration strategy to obtain full approval of mirvetuximab soravtansine as single-agent therapy.

FORWARD I is a registration trial in which 333 patients will be randomized 2:1 and will receive either mirvetuximab soravtansine or the physicians' choice of therapy (Doxil, paclitaxel, or topotecan). The study is currently enrolling in North America and Europe, with more than 100 sites expected to be activated in these geographies.

Mark Enyedy, ImmunoGen's president and chief executive officer, said: "The Phase 1 expansion cohort data being presented at ASCO support the potential of mirvetuximab soravtansine in the patient population eligible for FORWARD I.

"With the safety and efficacy profile demonstrated by these data, we look forward to completing enrollment in FORWARD I and evaluating mirvetuximab soravtansine with other therapies, including novel agents, in earlier lines of treatment."

Source: Company Press Release