CHICAGO – Twice as many patients with folate receptor alpha (FRα)-positive, advanced platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer responded to ImmunoGen's monoclonal antibody Elahere (mirvetuximab soravtansine-gynx) than did patients on chemotherapy in a confirmatory Phase III trial.
The US Food and Drug Administration granted Elahere accelerated approval in the US last year in this patient population based on data from a Phase II single-arm study. The MIRASOL trial is a global confirmatory study that could support regulatory submissions seeking full approval of the drug in the US as well as lead to regulatory filings in other countries, said Kathleen Moore, associate director of clinical research at the University of Oklahoma's Stephenson Cancer Center, who presented the MIRASOL results at the American Society of Clinical Oncology's annual meeting on Sunday.
The positive results from the trial showing Elahere's benefit over standard-of-care chemotherapy are "practice changing," Moore said. "There has never been a presentation of a clinical trial of a novel agent in the platinum-resistant ovarian cancer space that has demonstrated improvement in overall survival [over chemo] until now," she continued.
In MIRASOL, Elahere was compared to investigator's choice of chemo, which included paclitaxel, pegylated liposomal doxorubicin, or topotecan. The analysis presented at ASCO included data from 453 patients, half of whom were treated with Elahere. Patients were centrally screened and determined to be biomarker high if they had an immunohistochemistry score of 2+ in 75 percent of tumor cells for FRα expression. Moore added that 90 percent of ovarian cancers express FRα and 35 percent have high FRα expression.
Elahere outperformed chemo in MIRASOL, demonstrating a median progression-free survival of 5.6 months compared to 4 months. Patients on Elahere also lived longer compared to those on chemo, with a median overall survival of 16.5 months versus 12.8 months.
"There was a 35 percent reduction in the risk of progression or death with use of mirvetuximab as compared to investigators choice of chemotherapy," Moore said.
Twice as many patients also responded to Elahere, which had a 42.3 percent response rate in the trial compared to a 15.9 percent response rate with chemo. Elahere also led to a complete response in 12 patients, or 5.3 percent of those who received the drug.
Patients in the MIRASOL trial were heavily pretreated, having received between one and three lines of chemotherapy; more than half the patients had received Genentech's Avastin (bevacizumab) or PARP inhibitor treatment previously. Even in this heavily pretreated group, the drug continued to show benefit. According to Roisin O'Cearbhaill, research director of gynecologic medical oncology service at Memorial Sloan Kettering Cancer Center, these data suggest that Elahere could be effective in earlier lines of therapy; O'Cearbhaill was not involved with the trial.
"Bearing in mind that these patients had received up to three prior lines of therapy, it is interesting to note that patients who had not received prior bevacizumab appeared to drive a more substantial benefit from mirvetuximab. So, should we be using mirvetuximab earlier in the disease course?" O'Cearbhaill wondered. She added during her discussion of the MIRASOL data that there is an ongoing study, the Phase III GLORIOSA trial, evaluating Elahere with Avastin in patients with FRα-positive, platinum sensitive recurrent ovarian cancer, which could provide insight into the efficacy of ImmunoGen's drug in earlier lines.
Moore noted that patients on Elahere had less serious adverse events and fewer discontinuations compared to patients on chemo. There were fewer hematologic toxicities, incidence of alopecia, and peripheral neuropathy on Elahere than on chemo, though there were similar rates of gastrointestinal events in the two arms. Elahere caused ocular disorders in some patients, an adverse event that has been previously reported, but Moore said there are mitigation strategies for addressing this toxicity.
"Mirvetuximab is so well tolerated and it works [in this biomarker-selected group], so patients can recover from being hammered by paclitaxel, carboplatin, [or] whatever prior treatment they were on," Moore said. "When they finish [Elahere treatment] and they do eventually progress, they feel better and they can actually tolerate other therapies after. If you use a medicine that works and has a differentiated safety profile, patients can recover to go on to receive the next thing that may help them live longer."
While Elahere was the first drug approved in the US for FRα-positive advanced ovarian cancer, there are several others in development. Eisai is studying MORAb-202, which was licensed by Bristol Myers Squibb last year, in earlier stage studies in FRα-positive solid tumors, including endometrial, ovarian, lung, and breast cancers. Sutro Biopharma is also studying its antibody-drug conjugate, STRO-002, in a Phase I trial in ovarian and endometrial cancers.
O'Cearbhaill noted that questions remain about the activity of these novel antibody-drug conjugates in ovarian cancer that will hopefully be answered in future trials.
"Mirvetuximab has truly found its place and is well established now as an FDA-approved treatment for recurrent platinum-resistant ovarian cancer," she said. "That said, we still need more effective treatment options. We need options that not only show impressive response rates like this, but that translate into meaningful and durable responses for our patients."
She hopes to see more data on managing toxicity for these treatments along with data from studies exploring these drugs in earlier therapy lines.
"As we move forward with novel antibody-drug conjugates, it's going to become particularly important that we tease out exactly what level of [FRα] expression is required and which patients are most likely to derive benefit," she added. "We clearly need to develop reliable predictive biomarkers that will be able to predict patients who are likely to respond, as well as identify patients who will not respond to the treatment and would only be exposed to toxicity."