Final PICCOLO Data Underscore Mirvetuximab Soravtansine’s Efficacy in Later-Line Frα+ Platinum-Sensitive Ovarian Cancer

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Mirvetuximab soravtansine-gynx (Elahere) continued to showcase notable efficacy and consistent safety in patients with FRα-positive, third line or later recurrent platinum-sensitive ovarian cancer (PSOC), according to data from the final analysis of the single-arm phase 2 PICCOLO study (NCT05041257).1

Data presented during the 2025 ESMO Gynaecological Cancers Congress showed that at a median follow-up of 26.55 months (95% CI, 25.23-28.81), the median overall survival (OS) was 27.17 months (95% CI, 23.79-not reached [NR]) in the overall population (n = 79). The objective response rate (ORR) was 51.9% (95% CI, 40.4%-63.3%), the median duration of response (DOR) was 8.25 months (95% CI, 5.55-10.78), and the median progression-free survival (PFS) was 6.93 months (95% CI, 5.85-9.59).

In those who did not have prior exposure to a PARP inhibitor (n = 12), the ORR was 75.0% (95% CI, 42.8%-94.5%), the median DOR was 8.77 months (95% CI, 3.52-15.18), the median PFS was 10.02 months (95% CI, 6.87-15.31), and the median OS was 27.89 months (95% CI, 15.31-NR). In those who previously received PARP inhibitor treatment (n = 64), the ORR was 46.9% (95% CI, 34.3%-59.8%), the median DOR was 8.25 months (95% CI, 5.45-10.78), the median PFS was 6.87 months (95% CI, 5.55-8.90), and the median OS was 27.17 months (95% CI, 23.79-NR). Lastly, in those who experienced progressive disease with a PARP inhibitor (n = 59), the ORR was 45.8% (95% CI, 32.7%-59.2%), the median DOR was 7.33 months (95% CI, 5.03-10.78), the median PFS was 6.18 months (95% CI, 5.55-8.41), and the median OS was 27.04 months (95% CI, 22.14-NR).

“At final analysis of PICCOLO with 2-year follow-up in a heavily pretreated PSOC population, median OS was 27.17 months, with consistent median OS in those who may have PARP inhibitor–resistant tumors,” Angeles Alvarez Secord, MD, MHSc, of Duke Cancer Institute, in Durham, North Carolina, said in a presentation of the data. “These data suggest that mirvetuximab soravtansine is an efficacious treatment option in later-line, Frα-positive, PSOC. Additional studies with mirvetuximab soravtansine in PSOC are ongoing.”

Paving the Path to PICCOLO

Mirvetuximab soravtansine is a first-in-class antibody-drug conjugate (ADC) consists of an FRα-binding antibody, cleavable linker, and the maytansinoid DM4. In November 2022, the agent was granted accelerated approval for use in adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received 1 to 3 systemic treatment regimens.2 The ADC received full approval in March 2024 for this indication based on findings from the phase 3 MIRASOL study (NCT04209855).3

Findings from a Medidata pooled clinical trials analysis of patients with second-line or -later PSOC (n = 130) showed that the ADC elicited an ORR of 16.9% (95% CI, 10.9%-24.5%), and led to a median PFS of 6.11 months (95% CI, 5.06-7.39) and a median OS of 19.35 months (95% CI, 17.77-22.08).4

A Quick Preview of PICCOLO: Design, Objectives, and Prior Data

The open-label, single-arm trial enrolled patients with platinum-sensitive disease, FRα positivity by immunohistochemistry, who had received at least 2 previous platinum-containing regimens.1 For those with BRCA-mutated disease, patients needed to have previously received PARP inhibitors. Previous exposure to bevacizumab (Avastin) was not required.

Participants received mirvetuximab soravtansine at 6 mg/kg per adjusted ideal body weight every 3 weeks. Treatment continued until progressive disease, intolerable toxicity, withdrawn consent, or death. The primary end point was investigator-assessed ORR, and a key secondary end point was investigator-assessed DOR. Other secondary end points included PFS, OS, safety and tolerability, CA-125 response, and sensitivity analyses.

Earlier data from PICCOLO showed that at a median follow-up of 16.36 months (95% CI, 11.07-16.59), the agent induced an ORR of 51.9% (95% CI, 40.4%-63.3%), which comprised 6 confirmed complete responses.5 The median DOR was 8.25 months (95% CI, 5.55-10.78) with the ADC. Moreover, the median PFS was 6.93 months (95% CI, 5.85-9.59). OS data were not yet mature.

The data cutoff date for the final analysis was January 24, 2025.1 The median patient age was 66 years (range, 41-84) and 82.3% were White. Most patients did not have BRCA mutations or had unknown status (72.2%). More than half of patients (65.9%) received 1 to 2 prior lines of systemic therapy and 34.2% received 3 or more prior lines. The majority of patients had prior exposure to taxanes (97.5%); 25.3% were exposed in several lines. Eighty-one percent of patients had prior exposure to PARP inhibitors and 74.7% had progressed on them. More than half of patients (64.6%) had previously received bevacizumab. Lastly, 54.4% of patients had a most recent platinum-free interval of 12 months or less.

Seventy-seven percent of patients received a new anticancer therapy, which included platinum-based regimens (47%), gemcitabine (32%), anthracyclines (30%), other chemotherapy (28%), bevacizumab (25%), and taxanes (23%).

Safety Spotlight

“The safety profile of mirvetuximab soravtansine was consistent with the primary analysis in recurrent PSOC and prior clinical trials in platinum-resistant ovarian cancer showing a differentiated safety profile consisting primarily of low-grade gastrointestinal [toxicities], peripheral neuropathy, and resolvable ocular adverse effects [AEs],” Secord said.

In the final analysis, 99% experienced any treatment-emergent AEs; 47% of these effects were grade 3, 3% were grade 4, and 3% were grade 5. Serious AEs occurred in 22% of patients and 11% of them were related to treatment. TEAEs resulted in dose modification, reduction, or delay/hold for 66%, 43%, and 61%, respectively. TEAEs led to discontinuation for 16% of patients and 3% proved fatal. Treatment-related AEs led to 1 death.

Disclosures: Secord disclosed that institution received clinical trial grant funding from AbbVie, Aravive Inc, AstraZeneca, Clovis Oncology, Eisai Co Ltd, Ellipses Pharma Ltd, Roche/Genentech Inc, Genmab, GSK, ImmunoGen Inc, Karyopharm Therapeutics Inc, Merck, Mersana Therapeutics Inc, Myriad, OncoQuest Pharmaceuticals/Canariabio Inc, Seagen Inc, TORL Biotherapeutics, VBL Therapeutics, and Zentalis Pharmaceuticals. She disclosed onsulting fees from The GOG Foundation, AbbVie, and GSK; stock options in Amgen and Johnson & Johnson, divested; royalties from UpToDate; honoraria for lectures from Research to Practice, Clinical Care Options, Curio, HMP Global, Imedex, and GOG Foundation. She participates on clinical trial steering committees (uncompenstated) for the AtTEnd trial, OVAL trial, FLORA-5 trial, and QPT-ORE-004 trial. She also participates on the AAOGF Board of Trustees, SGO Board of Directors, FWC Board of Directors, and GOG Foundation Board of Directors.

References

1. Secord AA, Lewin S, Murphy CG, et al. Final analysis of the single-arm phase 2 PICCOLO trial of mirvetuximab soravtansine (MIRV) in folate receptor alpha (FRα)-positive, third-line and later, recurrent platinum-sensitive ovarian cancer (PSOC). Presented at: 2025 ESMO Gynaecological Cancers Congress; June 19-21, 2025. Abstract 76MO.
2. ImmunoGen announces FDA accelerated approval of Elahere (mirvetuximab soravtansine-gynx) for the treatment of platinum-resistant ovarian cancer. News release. ImmunoGen Inc. November 14, 2022. Accessed June 23, 2025. https://news.abbvie.com/2022-11-14-ImmunoGen-Announces-FDA-Accelerated-Approval-of-ELAHERE-TM-mirvetuximab-soravtansine-gynx-for-the-Treatment-of-Platinum-Resistant-Ovarian-Cancer
3. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. Accessed March 22, 2024. Accessed Kune 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian
4. Coleman RL, Ports K, Gradinariu V, et al. Efficacy of third-line and later (3L+) therapies post poly (ADP-ribose) polymerase inhibitor (PARPi) exposure in recurrent platinum-sensitive ovarian cancer (PSOC): A pooled clinical trial database analysis. J Clin Oncol. 2025;43(suppl 16):5579. doi:10.1200/JCO.2025.43.16_suppl.5579
5. Secord AA, Lewin SN, Murphy CG, et al. The efficacy and safety of mirvetuximab soravtansine in FRa-positive, thirdline and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial. Ann Oncol. 2025;36(3):321-330. doi:10.1016/j.annonc.2024.11.011