Elahere demonstrates 35% reduction in the risk of disease progression or death v.chemotherapy in FRalpha-positive platinum-resistant ovarian cancer

The results are being presented by Dr. Kathleen Moore in a late-breaking oral abstract session today at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. These data have also been selected for the 2023 Best of ASCO program, which will be held this summer following the ASCO Annual Meeting.

"I am thrilled to share these impressive results from the confirmatory MIRASOL trial at ASCO, which further demonstrate the potential of Elahere to become the new standard of care for patients with FRalpha positive PROC," said Kathleen Moore, Associate Director of Clinical Research and Director of the Oklahoma TSET/Sarah Cannon Phase I Program, Professor of the Section of Gynecologic Oncology at The University of Oklahoma and MIRASOL Principal Investigator. "As we saw in the top-line data announced last month, Elahere demonstrated an improvement versus chemotherapy across all efficacy endpoints and, importantly, is the first treatment to show an overall survival benefit in this patient population. The 33% reduction in the risk of death, along with the differentiated and well-characterized safety profile seen in MIRASOL, reinforce the potential of Elahere to serve as a transformative option for ovarian cancer patients and change how this disease is treated."

MIRASOL is a randomized Phase III trial of Elahere versus investigator's choice (IC) of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan). Eligibility criteria include patients with PROC whose tumors express high levels of FRalpha, using the Ventana FOLR1 Assay, and who have been treated with up to three prior regimens. The primary endpoint of this trial is progression-free survival (PFS) by investigator assessment. Key secondary endpoints include objective response rate (ORR) and overall survival (OS).

MIRASOL enrolled 453 patients. Patients were stratified by number of prior lines of therapy (14% had one prior line of therapy, 40% had two prior lines of therapy, and 46% had three prior lines of therapy) and by IC chemotherapy, with paclitaxel as the most commonly chosen (41%), followed by PLD (36%) and topotecan (23%). 62% of patients received prior bevacizumab; 55% received a prior PARP inhibitor.

As of the data cutoff on March 6, 2023, the median follow-up time for OS was 13.1 months; 14% of patients on the Elahere arm remained on study drug compared to 3% on the IC chemotherapy arm.

i. Elahere demonstrated a statistically significant and clinically meaningful improvement in PFS by investigator assessment compared to IC chemotherapy, with a hazard ratio (HR) of 0.65 (95% confidence interval [CI]: 0.52, 0.81; p<0.0001), which represents a 35% reduction in the risk of tumor progression or death in the elahere arm compared to the ic chemotherapy arm. the median pfs in the elahere arm was 5.62 months (95% ci: 4.34, 5.95) compared to 3.98 months (95% ci: 2.86, 4.47) in the ic chemotherapy arm.

ii. Elahere demonstrated a statistically significant and clinically meaningful improvement in OS compared to IC chemotherapy. With 204 OS events reported as of March 6, 2023, the median OS was 16.46 months (95% CI: 14.46, 24.57) in the Elahere arm, compared to 12.75 months (95% CI: 10.91, 14.36) in the IC chemotherapy arm, with a HR of 0.67 (95% CI: 0.50, 0.89; p=0.0046). This represents a 33% reduction in the risk of death in the Elahere arm in comparison to the IC chemotherapy arm.

iii. ORR by investigator assessment in the Elahere arm was 42.3% (95% CI: 35.8%, 49.0%), including 12 complete responses (CRs), compared to 15.9% (95% CI: 11.4%, 21.4%), with no CRs, in the IC chemotherapy arm.

In addition to data on the primary and key secondary endpoints, further safety and efficacy analyses from MIRASOL will be presented: i. In the bevacizumab-naïve subset (n=172), the PFS HR was 0.66, (95% CI: 0.46, 0.94; p=0.0210); in the bevacizumab-pretreated subset (n=281), the PFS HR was 0.64 (95% CI: 0.49, 0.84; p=0.0011). ii. In the bevacizumab-naïve subset, the OS HR was 0.51 (95% CI: 0.31, 0.86; p=0.0099); in the bevacizumab-pretreated subset, the OS HR was 0.74 (95% CI: 0.54, 1.04; p=0.0789). PFS and ORR results by blinded independent central review (BICR) were concordant with investigator assessment. a. The HR for PFS by BICR was 0.72 (95% CI: 0.56, 0.92; p=0.0082). b. ORR by BICR in the Elahere arm was 36.1% (95% CI: 29.9, 42.7), including 16 complete responses (CRs), compared to 14.6% (95% CI: 10.3, 19.9), with 4 CRs, in the IC chemotherapy arm.

iv. Elahere was well-tolerated, consistent with the known safety profile seen in the broader development program. No new safety signals were identified in MIRASOL. a. Compared with IC chemotherapy, Elahere was associated with lower rates of grade 3 or greater treatment-emergent adverse events (TEAEs) (42% vs 54%) and serious adverse events (24% vs 33%). b. Dose delays due to TEAEs occurred in 54% of patients on both arms; dose reductions due to TEAEs occurred in 34% of Elahere treated patients vs 24% of IC chemotherapy patients; discontinuations due to TEAEs occurred in 9% of Elahere treated patients vs 16% of IC chemotherapy patients.

The safety profile of Elahere consists of predominantly low-grade ocular and gastrointestinal TEAEs. Detailed safety data will be presented, including rates of all grade and grade 3+ ocular, gastrointestinal, neuropathy, and hematologic TEAEs for Elahere vs IC chemotherapy (paclitaxel, PLD, topotecan).

"We are incredibly pleased the MIRASOL results were selected as a late-breaking presentation at ASCO," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "As the first novel therapy to extend overall survival in platinum-resistant disease, and with consistent efficacy regardless of prior bevacizumab use, Elahere is a much-needed advance in the ovarian cancer treatment paradigm. We look forward to submitting the MAA and sBLA for Elahere in the EU and US, respectively, during the second half of the year, and to progressing the broader Elahere development program as we work to deliver this biomarker-directed ADC to eligible patients."

In November 2022, the FDA granted accelerated approval for Elahere for the treatment of adult patients with FRalpha-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens based on ORR and duration of response data from the pivotal SORAYA trial.