The MIRASOL trial, which was presented at ASCO on June 4th, demonstrated a significant improvement in the primary outcome of progression-free survival (PFS) and also indicated a survival benefit. MIRASOL serves as the confirmatory trial for ELAHERE, an antibody-drug conjugate (ADC) that targets the folate receptor alpha (FRα). ELAHERE received accelerated approval from the US Food and Drug Administration in November 2022 for patients who have undergone one to three prior lines of therapy, based on the overall response rate (ORR) data obtained from the Phase III SORAYA trial. The primary objective of this trial is to evaluate PFS as assessed by the investigators. Noteworthy secondary endpoints include ORR and overall survival (OS). The presentation followed the earlier announcement of the MIRASOL data in May, with ImmunoGen describing the results as highly successful.
A total of 453 patients were enrolled in the MIRASOL trial. The patients were categorized based on the number of previous lines of therapy they had received: 14% had undergone one prior line, 40% had received two prior lines, and 46% had received three prior lines. Additionally, the patients were stratified based on the type of IC chemotherapy they had received, with paclitaxel being the most commonly chosen option (41%), followed by PLD (36%) and topotecan (23%). Among the patients, 62% had received prior treatment with bevacizumab, while 55% had been treated with a PARP inhibitor. As of the data cutoff on March 6, 2023, the median follow-up period for OS was 13.1 months. It was observed that 14% of patients in the ELAHERE arm continued to receive the study drug, compared to only 3% in the IC chemotherapy arm.
- ELAHERE showcased a substantial and statistically significant improvement in PFS as assessed by investigators when compared to IC chemotherapy. This improvement translated to a 35% decrease in the risk of tumor progression or mortality within the ELAHERE group, in comparison to the IC chemotherapy group. The median PFS for patients receiving ELAHERE was 5.62 months, while it was 3.98 months for those receiving IC chemotherapy.s
- ELAHERE exhibited a substantial and statistically significant improvement in OS when compared to IC chemotherapy, which was also clinically meaningful. As of March 6, 2023, with 204 recorded events related to OS, the median OS for patients in the ELAHERE arm was 16.46 months, whereas it was 12.75 months in the IC chemotherapy arm. This indicates a 33% reduction in the risk of mortality within the ELAHERE arm compared to the IC chemotherapy arm.
- In the ELAHERE arm, the ORR as assessed by investigators was 42.3%, which included 12 complete responses (CRs). In comparison, the IC chemotherapy arm had an ORR of 15.9% with no complete responses.
In addition to data on the primary and key secondary endpoints, further safety and efficacy analyses from MIRASOL were also presented:
- In the subset of patients who had not received bevacizumab before (n=172), the hazard ratio (HR) for PFS was 0.66. In the subset of patients who had been previously treated with bevacizumab (n=281), the HR for PFS was 0.64.
- In the subset of patients who had not received bevacizumab before, the HR for OS was 0.51. In the subset of patients who had been previously treated with bevacizumab, the HR for OS was 0.74.
- The results for PFS and ORR as assessed by a BICR were consistent with the investigator's assessment.
- The HR for PFS as assessed by BICR was 0.72.
- The ORR as assessed by BICR in the ELAHERE arm was 36.1%, which included 16 complete responses (CRs), compared to 14.6%, with 4 CRs, in the IC chemotherapy arm.
- ELAHERE was well-tolerated, with a safety profile consistent with what has been observed in the broader development program. No new safety concerns were identified in the MIRASOL trial.
- Compared to IC chemotherapy, ELAHERE was associated with lower rates of grade 3 or higher treatment-emergent adverse events (TEAEs) (42% vs. 54%) and serious adverse events (24% vs. 33%).
- Dose delays due to TEAEs occurred in 54% of patients in both treatment arms, while dose reductions due to TEAEs were observed in 34% of ELAHERE-treated patients and 24% of IC chemotherapy patients. Discontinuations due to TEAEs were reported in 9% of ELAHERE-treated patients and 16% of IC chemotherapy patients. The safety profile of ELAHERE primarily consists of low-grade ocular and gastrointestinal TEAEs.
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Based on the trial results, the company plans to seek marketing authorization in Europe and apply for a supplemental biologics license in the US to transition ELAHERE from its current status to full approval in the second half of 2023. These data will reinforce ImmunoGen's dedication to the clinical development program and support the expansion of this therapy's use in a wider range of patients, including those with platinum-sensitive diseases.
KOL insights
“Based on the data presented by Dr. Moore, I wonder, if should we be considering moving the treatment a little bit earlier in the disease course. Bearing in mind that these patients had received up to three prior lines of therapy, it is interesting to note that patients who have not received prior bevacizumab appear to derive more substantial benefit from mirvetuximab” –Expert Opinion.
“Mirvetuximab soravtansine is the first novel treatment to demonstrate a benefit in overall survival [OS] in platinum-resistant ovarian cancer in a phase 3 setting. These data we consider to be practice-changing and position mirvetuximab soravtansine to be the new standard of care for tumors that are FRα-high and platinum-resistant for women with ovarian cancer.”–Expert Opinion.
Conclusion
ELAHERE has shown superior outcomes in terms of both PFS and OS compared to the investigator's choice of chemotherapy, making it the first treatment to provide such benefits for FRα-positive platinum-resistant ovarian cancer. The impressive efficacy data, combined with its well-established safety profile, establish mirvetuximab soravtansine as a new standard of care for patients with FRα-positive platinum-resistant ovarian cancer.
In December, ImmunoGen initiated the Phase III GLORIOSA trial, which aims to evaluate the combination of ELAHERE and AVASTIN compared to AVASTIN alone as a maintenance treatment for platinum-sensitive ovarian cancer. The study plans to enroll 418 patients and is projected to be completed by 2029, with primary outcome results expected in 2027.
ELAHERE is the first ADC for ovarian cancer with proven efficacy and is the only FDA-approved biomarker-directed therapy for platinum-resistant ovarian cancer. However, as major pharmaceutical companies like Mersana Therapeutics, Eisai, and Sutro BioPharma are also developing clinical-stage ADCs to target platinum-resistant ovarian cancer, ImmunoGen's ELAHERE might face tough competition and potentially be overshadowed
