ImmunoGen saw its shares lose more than half their value this morning after it acknowledged the failure of its lead antibody-drug conjugate mirvetuximab soravtansine (IMGN853) failed a Phase III trial in patients with folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer.

Mirvetuximab soravtansine missed its primary endpoint in the Phase III FORWARD I trial (NCT02631876) of progression-free survival (PFS) in either the entire study population or the pre-specified subset of patients with high FRα expression.

For the entire study population, the confirmed overall response rate (ORR) was higher for mirvetuximab soravtansine than for chemotherapy (22% vs 12%), with no significant difference in the primary endpoint of PFS (HR 0.98) or overall survival (HR 0.81).

For the 218 patients in the pre-specified high FRα subgroup, ImmunoGen said, PFS was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.69, p-value 0.049). However, the study required the p-value in the high subset to be less than or equal to 0.025 to achieve statistical significance.

“This study with mirvetuximab did not result in the outcome that we had hoped for in platinum-resistant patients,” ImmunoGen president and CEO Mark Enyedy said in a statement. “We will further assess the data from FORWARD I to determine potential next steps with a monotherapy approach.”

He added that ImmunoGen has generated encouraging data with mirvetuximab combination regimens, “and will evaluate our ongoing studies as an independent path forward to support a registration in ovarian cancer.”

ORR was longer in patients who received mirvetuximab soravtansine (24%) compared with chemotherapy (10%), while overall survival was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.62, p-value 0.033), ImmunoGen said, adding that it intends to present additional results from FORWARD I at an unspecified upcoming medical meeting.

“Based upon the efficacy signals we observed in the high FRα subset with PFS, confirmed overall response rate and overall survival, we are conducting additional analyses to further evaluate the potential benefit of mirvetuximab soravtansine for FRα-positive platinum-resistant ovarian cancer,” added Anna Berkenblit, MD, senior vice president and chief medical officer of ImmunoGen.

Shares plummet 51%

Investors responded to the Phase III failure with a stock selloff that sent ImmunoGen shares plummeting 51% from yesterday’s closing price of $4.72, to $2.30 in early market trading as of 9:50 a.m.

ImmunoGen partnered with the GOG Foundation on FORWARD I, which was conducted in North America and Europe. FORWARD I randomized 366 patients to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel), on a 2:1 basis. Eligibility criteria included patients with platinum-resistant ovarian cancer that expressed medium or high levels of FRα who had been treated with up to three prior regimens.

The study’s PFS primary endpoint was assessed using the Hochberg procedure for both the entire study population and the subset of high-FRα expression patients, enabling simultaneous testing of two overlapping populations.

According to ImmunoGen, mirvetuximab soravtansine is the first FRα-targeting ADC. It uses a humanized FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.

ImmunoGen is also studying mirvetuximab soravtansine in combination regimens for both platinum-resistant and platinum-sensitive disease in the Phase Ib/II FORWARD II trial (NCT02606305), for which the company reported positive data last year.

In FORWARD II, mirvetuximab soravtansine  is being assessed in combination with Genentech (Roche)’s Avastin® (bevacizumab), carboplatin, or Merck & Co.’s Keytruda® (pembrolizumab) in patients with FRα-positive platinum-resistant ovarian cancer, primary peritoneal, or fallopian tube tumors, as well as a triplet combination of mirvetuximab plus carboplatin and Avastin in patients with platinum-sensitive ovarian cancer.

ImmunoGen is recruiting patients for two additional Phase I trials for mirvetuximab soravtansine, according to ClinicalTrials.gov. One study is designed to assess the side effects and best dose of mirvetuximab soravtansine and rucaparib camsylate in treating participants with endometrial, ovarian, fallopian tube, or primary peritoneal cancer that has come back (NCT03552471). The other study is designed to evaluate the side effects and best dose of mirvetuximab soravtansine and gemcitabine hydrochloride in treating patients with folate receptor (FR) alpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer that has come back (NCT02996825)

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