Combining Immunogen‘s mirvetuximab soravtansine, an investigational antibody-drug conjugate, with Avastin (bevacizumab) showed signs of favorable efficacy and demonstrated a manageable safety profile in patients with platinum-resistant ovarian cancer, according to data from a Phase 1/2 clinical trial.
In addition, initial data from a Phase 1 trial also indicates that adding mirvetuximab to gemcitabine has acceptable safety and favorable anti-tumor activity for folate receptor alpha (FRα)-positive, and recurrent epithelial ovarian, endometrial, or triple-negative breast cancers.
These updates will be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31–June 4 in Chicago.
Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate targeting folate receptor alpha, a protein expressed at the surface of many ovarian cancers, as well as other types of solid tumors. It is a hybrid molecule where an anti-FRα antibody is linked to a potent tumor-killing agent, DM4.
The Phase 1/2 trial (NCT02606305), called FORWARD II, is addressing the safety and preliminary efficacy of different combination regimens of mirvetuximab soravtansine plus chemotherapy, for patients with FRα-positive advanced epithelial ovarian cancer, primary peritoneal, or fallopian tube tumors. The study is still recruiting at sites in the U.S., Canada, and Europe.
Updated trial data for the mirvetuximab-Avastin combination will be presented at ASCO by David M. O’Malley, MD, from the Ohio State University College of Medicine, in the poster “Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study.”
In this report, researchers analyzed the response of 66 patients with FRα-positive, platinum-resistant ovarian cancer who were assigned mirvetuximab soravtansine plus Avastin.
Patients were given intravenous (into-the-vein) infusions of mirvetuximab and Avastin on the first day of each 21-day cycle. Participants had been heavily pretreated with a median of three prior lines of therapy, and 62% had already been on Avastin.
The combination led to some level of tumor reduction in 39% of the patients, and led to a median survival without disease progression of 6.9 months. Anti-tumor responses lasted for a median of 8.6 months.
The regimen was even more beneficial for a specific group of 16 patients, who had never been on Avastin, had one to two prior therapies, and expressed medium to high levels of FRα. In this population, 56% of the patients responded to the treatment and reduced their tumor burden.
Consistent with this response, those patients lived longer without signs of disease worsening (median of 9.9 months) and also tended to have more durable responses (median of 12 months).
In terms of safety, the combination continues to show a safety profile in line with the known profiles for each agent, with no new safety signals observed. Most adverse events were mild to moderate, including diarrhea (58%), nausea (50%), and blurred vision (48%). Serious events were primarily gastrointestinal, namely small intestinal obstruction in four patients (6%).
“We are pleased that the combination of mirvetuximab plus Avastin has generated significant anti-tumor activity in patients with platinum-resistant disease, with trends toward deeper, more durable responses seen in individuals with higher FRα expression and a favorable tolerability profile,” Anna Berkenblit, MD, vice president and chief medical officer of ImmunoGen, said in a press release.
“The outcomes observed in patients with medium or high FRα expression are encouraging with respect to those reported in similar patient populations for Avastin plus chemotherapy,” she said.
“Our goal remains to establish mirvetuximab as the combination agent of choice in ovarian cancer, supporting its use in earlier lines of therapy. These mature data support further exploration of this doublet, as well as the ongoing expansion study evaluating a triplet combination of mirvetuximab with Avastin and carboplatin in patients with platinum-sensitive disease,” she added.
In addition, Mihaela C. Cristea, MD, from City of Hope, will present preliminary results of the mirvetuximab-gemcitabine combo in the poster “A phase I study of mirvetuximab soravtansine (IMGN853) and gemcitabine (G) in patients with FOLR1-positive recurrent epithelial ovarian (EOC), endometrial cancer (EC), or triple-negative breast cancer (TNBC).”
Data was obtained in a Phase 1 trial (NCT02996825) that is primarily addressing the safety and optimal dose of mirvetuximab soravtansine plus gemcitabine hydrochloride for treating patients with FRα-positive epithelial ovarian, endometrial, or triple-negative breast cancer whose disease returned after treatment. In the case of ovarian cancer, patients must have platinum-resistant disease.
To date, a total of 15 patients, 10 of whom have ovarian cancer, have been treated with infusions of mirvetuximab soravtansine and gemcitabine in 21-day cycles. Initial results show that the combination regimen is achievable at clinically relevant doses, with a safety profile that agrees with that expected for both agents.
In addition, Immunogen reports the combination showed encouraging preliminary anti-tumor activity for all three tumor types. Researchers are now enrolling patients at the recommended Phase 2 dose (usually the highest dose with acceptable toxicity), and maximum tolerated doses were to be determined before May.