Elahere Achieves Primary, Key Secondary Endpoint in Phase II Trial Treating Platinum-Sensitive Ovarian Cancer

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Elahere (mirvetuximab soravtansine; AbbVie) achieved both the primary and secondary endpoints of the Phase II PICCOLO trial (NCT05041257) in heavily pre-treated patients with folate receptor-alpha (FRα) positive, platinum-sensitive ovarian cancer (PSOC).¹

The FDA granted accelerated approval to Elahere in November 2022 for adults with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who were previously administered one to three systemic treatment regimens. The agency upgraded the regulatory action to a full approval in March 2024.^2,3

"Significant unmet needs remain for patients with platinum sensitive disease, as each subsequent line of therapy in this setting is associated with decreased efficacy and tolerability, which reinforces the need for treatment alternatives for these patients," Angeles Alvarez Secord, MD, MHSc, of the Duke Cancer Institute, said in a press release. "The PICCOLO data further support the potential of [Elahere] for platinum-sensitive ovarian cancer patients."¹

An investigational, first-in-class antibody drug conjugate, Elahere is comprised of a folate receptor alpha-binding antibody, cleavable linker, and maytansinoid payload DM4, to eliminate targeted cancer cells. The single-arm, PICCOLO trial analyzed the efficacy and safety of Elahere monotherapy in patients with FRα-high, PSOC who were previously administered at least two lines of platinum-containing therapy or who have documentation of a platinum allergy.

The trial’s primary endpoint is objective response rate (ORR), with duration of response (DOR) serving as a key secondary endpoint and additional secondary endpoints of treatment-emergent adverse effects, CA-125 level, progression-free survival, and overall survival.

Enrollment criteria included being at least 18 years of age with a confirmed diagnosis of high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer; having platinum-sensitive disease defined as radiographic progression more than six months from the last dose of the most recently administered platinum therapy; at least one measurable lesion per RECIST 1.1 criteria; FRα positivity defined by Ventana FOLR1 assay; and ECOG performance status of zero or one.⁴

The trial was designed to statistically rule out an ORR of 28% or under, as per the lower bound of the confidence interval (CI), which was previously observed with non-platinum, single-agent chemotherapy in patients with platinum-sensitive disease, according to AbbVie.¹

“Patients with PSOC with multiple prior lines of platinum-based therapy or who are ineligible for platinum-based therapy, as in the population in PICCOLO, have no established benchmark standard of care, particularly after disease progression on a PARP inhibitor,” AbbVie stated in the release.¹

The results of the trial show an ORR of 51.9% (95%CI 40.4 – 63.3%) and median DOR of 8.25 months, which achieved both the primary and key secondary endpoints, respectively. In terms of safety, the profile of Elahere was consistent with what has been reported in prior clinical trials, with no new safety signals identified.

The most fatal gynecological cancer, ovarian cancer, is often diagnosed in the late stage, with approximately 20,000 patients diagnosed annually and 13,000 deaths. Standard of care treatment is surgery and platinum-based chemotherapy; however, many patients develop difficult to treat platinum-resistant disease that reduces their response rates, representing a significant unmet need.

Full data from the PICCOLO trial will be presented at an upcoming medical meeting, according to AbbVie.

References

1. 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 June 7, 2024. 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

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 June 7, 2024. 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 June 7, 2024. 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

4. Mirvetuximab soravtansine monotherapy in platinum-sensitive epithelial, peritoneal, and fallopian tube cancers (PICCOLO). ClinicalTrials.gov. Updated April 22, 2024. Accessed June 7, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05041257