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The U.S. Food and Drug Administration (FDA) has granted full approval for mirvetuximab soravtansine-gynx (Elahere®; ImmunoGen, [now a part of AbbVie]) for the treatment of folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal adult cancer patients treated with up to three prior therapies. [1][2]

Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate or ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. [1][2]

Ovarian cancer is the leading cause of death from gynecological cancers in the United States. Each year, approximately 20,000 patients are diagnosed.

Patients often present with late-stage disease, undergo surgery and are then treated with platinum-based chemotherapy.

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Unfortunately, the majority of patients eventually develop platinum-resistant disease, which is difficult to treat. In this setting, standard of care single-agent chemotherapies are associated with low response rates, short durations of response, and significant toxicities.  If patient’s become resistant to treatment they may require another therapy, such as mirvetuximab soravtansine.

“The full FDA approval of ELAHERE for eligible patients with ovarian cancer represents the culmination of years of work by the ImmunoGen team. Mirvetuximab soravtansine-gynx is the first and only antibody-drug conjugate (ADC) approved in the U.S. for this difficult-to-treat malignancy,” said Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, AbbVie.

MIRASOL Study
Mirvetuximab soravtansine was first granted FDA accelerated approval in November 2022 and the conversion to full approval is based on data from the confirmatory Phase 3 MIRASOL trial (Study 0416: NCT04209855), a multicenter, open-label, active-controlled, randomized, two-arm trial with 453 patients diagnosed with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were permitted to receive up to three prior lines of systemic therapy.

In this study, investigators evaluated the efficacy of the drug and compared mirvetuximab soravtansine to investigator’s choice (IC) of chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan), in patients with platinum-resistant ovarian cancer (PROC) whose tumors express high levels of FRα and who have been treated with up to three prior therapies.

Eligibility criteria include patients with PROC whose tumors express high levels of FRα, using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, and patients 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). The trial enrolled 453 patients.

Patients were stratified by number of prior lines of therapy (14% had one prior line of therapy, 39% had two prior lines of therapy, and 47% 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.

Patients were further randomized (1:1) to receive mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) as an intravenous infusion every 3 weeks or investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) until disease progression or unacceptable toxicity.

The primary endpoint of MIRASOL was progression-free survival (PFS) by investigator assessment and key secondary endpoints included objective response rate (ORR) and overall survival (OS).

The results from this trial satisfy the post-marketing requirement of the previous accelerated approval for mirvetuximab soravtansine-gynx.

More about outcomes
The major efficacy outcome measures were overall survival (OS), investigator-assessed progression-free survival (PFS) and confirmed overall response rate (ORR) per investigator assessment. PFS and ORR were evaluated according to RECIST, version 1.1.

Median OS was 16.5 months (95% CI: 14.5, 24.6) in the mirvetuximab soravtansine-gynx arm and 12.7 months (95% CI: 10.9, 14.4) in the chemotherapy arm (Hazard Ratio [HR] 0.67 [95% CI: 0.50, 0.88] p-value 0.0046). Median PFS was 5.6 months (95% CI: 4.3, 5.9) and 4.0 months (95% CI: 2.9, 4.5) (HR 0.65 [95% CI: 0.52, 0.81] p-value <0.0001) for the respective arms. ORR was 42% (95% CI: 36, 49) and 16% (95% CI: 12, 22) (p-value <0.0001), respectively.

Mirvetuximab soravtansine showed overall fewer Grade 3+ adverse events and a lower rate of discontinuations due to adverse events when compared to the IC chemotherapy control group.

Adverse events
The most common (≥20%) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

“As the first treatment to show a statistically significant overall survival benefit in patients with platinum-resistant ovarian cancer, mirvetuximab soravtansine provides an effective new option for patients with folate receptor alpha positive tumors. These patients previously had very limited options and mirvetuximab soravtansine changes that,” said Kathleen Moore, deputy director and associate director of clinical research at the Stephenson Cancer Center of The University of Oklahoma and MIRASOL principal investigator.

European approval
The Marketing Authorization Application (MAA) for ELAHERE in Europe has been accepted by the European Medicines Agency (EMA). Regulatory submissions for ELAHERE are also under review in multiple other countries.

Clinical trials
A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (MIRASOL) –
ClinicalTrials.gov ID: NCT04209855

Highlights of prescribing information
Mirvetuximab soravtansine-gynx (Elahere®; ImmunoGen, [now a part of AbbVie]) [Prescribing Information]

Reference
[1] Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estévez-García P, Coffman L, Nicum S, Duska LR, Pignata S, Gálvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. doi: 10.1056/NEJMoa2309169. PMID: 38055253.
[2] Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. doi: 10.1200/JCO.22.01900. Epub 2023 Jan 30. PMID: 36716407; PMCID: PMC10150846.

Featured Image: Teal ribbon awareness to support Ovarian/Cervical Cancer on human hand old aged wood background. Courtesy: © 2018. Fotolia/Adobe Used with permission

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