Final PICCOLO Data Highlight Efficacy of Mirvetuximab Soravtansine in Later-Line Frα+ Platinum-Sensitive Ovarian Cancer

This article was originally published on OncLive^® and has been lightly edited.

Mirvetuximab soravtansine-gynx (Elahere; AbbVie) continued to showcase notable efficacy and consistent safety in patients with folate receptor alpha–positive (FRα+), 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 European Society for Medical Oncology 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).

Mirvetuximab soravtansine continues to show efficacy and safety in the final analysis of the phase 2 PICCOLO study. | Image Credit: tashatuvango - stock.adobe.com

In those who did not have prior exposure to a poly-ADP-ribose polymerase (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). Conversely, among 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 during 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) that consists of an FRα-binding antibody, a cleavable linker, and the maytansinoid DM4. In November 2022, the agent was granted accelerated approval for use in adult patients with FRα+, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received 1 to 3 systemic treatment regimens.² The ADC later 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 trial 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 was not required.

Every 3 weeks, participants received mirvetuximab soravtansine at 6 mg/kg per adjusted ideal body weight. 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 PICCOLO data 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). However, the 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%), while 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%), with 25.3% exposed to multiple 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

In the final analysis, 99% experienced any treatment-emergent adverse effects (TEAEs); 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.

“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 AEs,” Secord said during the presentation.

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. Joszt L. FDA approves mirvetuximab soravtansine-gynx for platinum-resistant ovarian cancer. AJMC. November 15, 2022. Accessed June 25, 2025. https://www.ajmc.com/view/fda-approves-mirvetuximab-soravtansine-gynx-for-platinum-resistant-ovarian-cancer
3. McNulty R. Mirvetuximab soravtansine-gynx granted full FDA approval for FRα+ platinum-resistant ovarian cancer. AJMC. March 22, 2024. Accessed June 25, 2025. https://www.ajmc.com/view/mirvetuximab-soravtansine-gynx-granted-full-fda-approval-for-fr-platinum-resistant-ovarian-cancer
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