MIRASOL Trial Shows Elahere Significantly Improves Survival in Platinum-Resistant Ovarian Cancer

Credit: Lars Neumann | stock.adobe.com

Results from the Phase III MIRASOL trial (NCT04209855) show that Elahere (mirvetuximab soravtansine-gynx) produced a significant improvement in progression-free survival (PFS) and overall survival (OS) compared to chemotherapy in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer (PROC).^1,2 The findings highlight the potential of Elahere as a new standard of care for this difficult to treat disease, according to the trial investigators.

"Ovarian cancer can be devastating, and when cancer cells stop responding to chemotherapy patients may feel hopeless about their journey," Svetlana Kobina, MD, PhD, vice president, oncology medical affairs, AbbVie, said in a press release. “The data presented today reinforce the importance of ELAHERE as a transformative therapy for patients with limited options.”¹

The FDA granted accelerated approval to Elahere in November 2022 for adults with FRα-positive PROC, fallopian tube, or primary peritoneal cancer who were previously administered up to three systemic treatment regimens. The agency upgraded the regulatory action to a full approval in March 2024.^3,4

Elahere, an investigational, first-in-class antibody drug conjugate, is comprised of a folate receptor alpha-binding antibody, cleavable linker, and maytansinoid payload DM4, to eliminate targeted cancer cells. The single-arm, Phase II PICCOLO trial (NCT05041257) evaluated the efficacy and safety of Elahere monotherapy in patients with FRα-high, platinum-sensitive ovarian cancer who were previously administered at least two lines of platinum-containing therapy or who have documentation of a platinum allergy.^5,6

Elahere achieved both the primary endpoint of objective response rate (ORR), and the key secondary endpoint of duration of response, as well as additional secondary endpoints of treatment-emergent adverse effects (TEAEs), CA-125 level, PFS, and OS.

Trial Design

The randomized MIRASOL trial compared Elahere with investigator's choice of single-agent chemotherapy comprised of paclitaxel, pegylated liposomal doxorubicin, or topotecan. Enrollment criteria included having PROC with tumors that express high levels of FRα as determined by the Ventana FOLR1 RxDx Assay and who were previously administered up to three treatment regimens.

The MIRASOL trial’s primary endpoint was PFS as per investigator assessment, with key secondary endpoints that included ORR and OS. Investigators enrolled 453 patients, who were stratified as per previous lines of therapy, with 14% having one prior line of therapy, 39% with two prior lines of therapy, and 47% with three prior lines of therapy. Among these patients, 62% were previously treated with bevacizumab and 55% were previously treated with a PARP inhibitor. For patients randomly assigned to receive investigator's choice of chemotherapy, 41% were administered paclitaxel, 36% were administered pegylated liposomal doxorubicin, and 23% were administered topotecan.

At median follow up of 30.5-months, patients administered Elahere had a median PFS of 5.59 months compared to 3.98 months with chemotherapy, which translates to a 37% decrease in the risk of tumor progression or death (HR 0.63; [95% CI: 0.51, 0.79]). Patients administered Elahere achieved an ORR of 41.9% compared to 15.9% in the chemotherapy cohort.

Further, Elahere produced a clinically meaningful OS benefit, with a median of 16.85 months compared to a median of 13.34 months with chemotherapy, which translates to a 32% decrease in the risk of death (HR 0.68 [95% CI: 0.54, 0.84]).

In terms of safety, the most common TEAEs reported by at least 20% of patients administered Elahere were blurred vision, keratopathy, abdominal pain, fatigue, diarrhea, dry eye, constipation, nausea and peripheral neuropathy. Overall, patients in the Elahere cohort experienced lower rates of grade ≥3 TEAEs, serious AEs, and discontinuations because of AEs compared to patients in the chemotherapy cohort.

"The final data showcase the significant improvement in overall survival benefit of treatment with Elahere compared to standard of care chemotherapy," trial investigator and presenter, Toon Van Gorp, MD, PhD, professor of Gynecologic Oncology, University of Leuven, said in the release. "The significant improvements in survival, along with the well-characterized safety profile, reinforce Elahere as an emerging standard of care for difficult-to-treat ovarian cancer and warrants further study of this medicine in earlier treatment settings."¹

References

1. ELAHERE® (mirvetuximab soravtansine-gynx) Shows Consistent Survival Benefit in Long-Term Analysis for Certain Ovarian Cancer Patients. News release. AbbVie. March 15, 2025. Accessed March 17, 2025. https://news.abbvie.com/2025-03-15-ELAHERE-R-mirvetuximab-soravtansine-gynx-Shows-Consistent-Survival-Benefit-in-Long-Term-Analysis-for-Certain-Ovarian-Cancer-Patients

2. A Study of Mirvetuximab Soravtansine vs. Investigator's Choice (IC) of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha (FRα) Expression (MIRASOL). ClinicalTrials.gov. Updated January 7, 2025. Accessed March 17, 2025. https://clinicaltrials.gov/study/NCT04209855

2. ImmunoGen. ImmunoGen Announces FDA Accelerated Approval of ELAHERE™ (mirvetuximab soravtansine-gynx) for the Treatment of Platinum-Resistant Ovarian. News Release. November 15, 2022. Accessed March 17, 2025. https://www.businesswire.com/news/home/20221104005657/en

3. U.S. Food and Drug Administration (FDA) Grants Full Approval for ELAHERE® (mirvetuximab soravtansine-gynx) for Certain Ovarian Cancer Patients. AbbVie. March 22, 2024. Accessed March 17, 2025. https://news.abbvie.com/2024-03-22-U-S-Food-and-Drug-Administration-FDA-Grants-Full-Approval-for-ELAHERE-R-mirvetuximab-soravtansine-gynx-for-Certain-Ovarian-Cancer-Patients

5. AbbVie Announces Positive Topline Results from Phase 2 PICCOLO Trial Evaluating Mirvetuximab Soravtansine (ELAHERE®) for High Folate Receptor-Alpha (FRα) Expressing Platinum-Sensitive Ovarian Cancer. News release. AbbVie. June 6, 2024. Accessed March 17, 2025. https://news.abbvie.com/2024-06-06-AbbVie-Announces-Positive-Topline-Results-from-Phase-2-PICCOLO-Trial-Evaluating-Mirvetuximab-Soravtansine-ELAHERE-R-for-High-Folate-Receptor-Alpha-FR-Expressing-Platinum-Sensitive-Ovarian-Cancer

6. Mirvetuximab soravtansine monotherapy in platinum-sensitive epithelial, peritoneal, and fallopian tube cancers (PICCOLO). ClinicalTrials.gov. Updated April 22, 2024. Accessed March 17, 2025. https://classic.clinicaltrials.gov/ct2/show/NCT05041257