Mirvetuximab soravtansine in folate receptor alpha (FRα)-high platinum-resistant ovarian cancer: final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial.

The single-arm, phase II SORAYA trial (NCT04296890) of mirvetuximab soravtansine-gynx in folate receptor alpha (FRα)-high platinum-resistant ovarian cancer (n=105 (efficacy-evaluable)) met its primary endpoint with an objective response rate of 32.4% (95% CI, 23.6 to 42.2). Here we report final SORAYA trial results for overall survival and post hoc objective response rates in subgroups by sequence and number of prior therapies. Eligible patients had high-grade serous platinum-resistant ovarian cancer with high FRα expression and one to three prior therapies (prior bevacizumab required). Enrolled participants received 6 mg/kg mirvetuximab soravtansine-gynx adjusted ideal body weight intravenously once every 3 weeks until progressive disease, unacceptable toxicity, withdrawal of consent, or death. Final overall survival and post hoc objective response rates were assessed in efficacy-evaluable participants. The safety population included all patients who received ≥1 dose of mirvetuximab soravtansine-gynx. At data cut-off (December 22, 2022; n=105), final median overall survival was 15.0 months (95% CI, 11.5 to 18.7). Median overall survival in participants with one to two prior therapy lines was 18.7 months (95% CI, 13.8 to not estimable (NE)) and 11.6 months (95% CI, 7.1 to 16.7) with three prior therapy lines. Median overall survival was 15.0 months (95% CI, 11.5 to NE) in participants with prior poly (ADP-ribose) polymerase inhibitor (PARPi) treatment versus 14.0 months (95% CI, 7.1 to NE) in those without. Objective response rate (data cut-off: November 17, 2021) differed among participants who received mirvetuximab soravtansine-gynx as their first treatment in the platinum-resistant setting (34.8%; 95% CI, 23.5 to 47.6) versus a different first treatment (28.2%; 95% CI, 15.0 to 44.9) or had received prior bevacizumab in a platinum-sensitive (34.0%; 95% CI, 24.6 to 44.5) versus platinum-resistant setting (17.6%; 95% CI, 3.8 to 43.4). No new safety signals were observed. These results support the clinically meaningful efficacy of mirvetuximab soravtansine-gynx in FRα-expressing platinum-resistant ovarian cancer, irrespective of prior treatment or sequence.

Coleman RL ，Lorusso D ，Oaknin A ，Cecere SC ，Denys H ，Colombo N ，van Gorp T ，Konner JA ，Romeo Marin M ，Harter P ，Murphy C ，Wang Y ，Esteves B ，Method M ，Matulonis U ... -  《-》

The efficacy and safety of mirvetuximab soravtansine in FRα-positive, third-line and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial.

Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC). Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Primary endpoint was investigator-assessed objective response rate (ORR). Key secondary endpoint was investigator-assessed duration of response (DOR). Additional endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety. Analyses of subgroups by disease characteristics (e.g. platinum-free interval) and treatment history [e.g. prior bevacizumab and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) treatment] were exploratory. Seventy-nine participants were enrolled and efficacy assessable. The primary endpoint was met; ORR was 51.9% [95% confidence interval (CI) 40.4% to 63.3%]. Median DOR was 8.25 months (95% CI 5.55-10.78 months) and median PFS was 6.93 months (95% CI 5.85-9.59 months). OS was not mature at data cut-off. ORR was 45.8% (95% CI 32.7% to 59.2%) in participants with PD while on/within 30 days of prior PARPi (n = 59) and 60.0% (95% CI 14.7% to 94.7%) in those without PD with prior PARPi (n = 5). No new safety signals occurred; most common treatment-emergent adverse events (TEAEs) were gastrointestinal, neurosensory, and resolvable ocular events. TEAEs led to discontinuation in 13 participants (16%) and death in 2 participants (3%). MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi (NCT05041257).

Alvarez Secord A ，Lewin SN ，Murphy CG ，Cecere SC ，Barquín A ，Gálvez-Montosa F ，Mathews CA ，Konecny GE ，Ray-Coquard I ，Oaknin A ，Rubio Pérez MJ ，Bonaventura A ，Diver EJ ，Ayuk SM ，Wang Y ，Corr BR ，Salutari V ... -  《-》

Safety and tolerability of mirvetuximab soravtansine monotherapy for folate receptor alpha-expressing recurrent ovarian cancer: An integrated safety summary.

Mirvetuximab soravtansine-gynx (MIRV) is a novel antibody-drug conjugate targeting folate receptor alpha (FRα), which is overexpressed in epithelial ovarian cancer (EOC), with limited expression on normal tissues. This integrated safety summary sought to characterize the safety profile of MIRV monotherapy in participants with FRα-expressing recurrent EOC. Safety data were retrospectively analyzed from 4 clinical studies (phase 1 trial [NCT01609556], phase 3 FORWARD I [NCT02631876], phase 2 SORAYA [NCT04296890], phase 3 MIRASOL [NCT04209855]) that evaluated participants with FRα-expressing recurrent EOC who received ≥1 dose of MIRV 6 mg/kg adjusted ideal body weight every 3 weeks. In this analysis of 682 participants, 94 % had platinum-resistant ovarian cancer (PROC). Blurred vision (43 %), nausea (41 %), diarrhea (39 %), and fatigue (35 %) were the most common treatment-emergent adverse events (TEAEs) and were primarily grade 1-2 in severity. Grade ≥ 3 TEAEs occurred in 48 % of participants, with the most common being keratopathy and blurred vision (5 % each). Most TEAEs were managed with supportive care and dose modifications, and only 12 % of participants experienced a TEAE leading to discontinuation (1 % due to ocular events). No corneal ulcerations or perforations have been reported. Median time to onset of blurred vision and keratopathy was 5.9 and 6.7 weeks, respectively. Most blurred vision events and keratopathy events resolved completely (71 % and 66 %, respectively) or partially (15 % and 14 %, respectively). As demonstrated among 682 participants, the safety profile of MIRV is well tolerated and consists primarily of low-grade gastrointestinal, fatigue, headache, peripheral neuropathy, and resolvable ocular adverse events.

Moore KN ，Lorusso D ，Oaknin A ，Oza A ，Colombo N ，Van Gorp T ，O'Malley DM ，Banerjee S ，Murphy CG ，Harter P ，Konecny GE ，Pautier P ，Method M ，Wang Y ，Coleman RL ，Birrer M ，Matulonis UA ... -  《-》

Mirvetuximab soravtansine-gynx: first antibody/antigen-drug conjugate (ADC) in advanced or recurrent ovarian cancer.

Bogani G ，Coleman RL ，Vergote I ，van Gorp T ，Ray-Coquard I ，Oaknin A ，Matulonis U ，O'Malley D ，Raspagliesi F ，Scambia G ，Monk BJ ... -  《-》

Mirvetuximab Soravtansine in solid tumors: A systematic review and meta-analysis.

Mirvetuximab Soravtansine (MIRV) is a promising antibody‒drug conjugate (ADC) that targets folate receptor alpha (FRα), which is overexpressed in several types of solid tumors. In November 2022, MIRV was approved in the USA for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who received 1-3 prior systemic treatment regimens. Therefore, high-quality evidence for its efficacy and safety in different cancers is urgently needed. A systematic search (e.g., PubMed, Embase, Web Of Science, Cochrane Library) was conducted to identify all relevant clinical trials of MIRV alone or in combination with chemo- and/or target-therapies in solid tumors. The primary end-point was median progression-free survival (mPFS). The secondary endpoints were the Objective response rate (ORR) and adverse effects (AEs). A random-effects model was applied. The study included nine research studies with a total of 682 patients. The pooled mPFS and pooled ORR were 6.70 months (95% CI 4.54-8.86, I2 = 96.21%) and 36% (95% CI: 28% to 44%, I2 = 76.79%), respectively. Significant differences were observed among intervention regimens and response to platinum. The pooled mPFS of MIRV monotherapy and MIRV+ Bevacizumab (BEV) combined therapy was 4.28 (95% CI 3.90-4.65, I2 = 0.00%) and 7.78 (95% CI 6.62-8.95, I2 = 0.00%), respectively. The pooled ORRs of MIRV monotherapy and MIRV+BEV combined therapy were 25% (95% CI 21%-29%, I2 = 25.20%) and 43% (95% CI 36%-50%, I2 = 0.01%), respectively. The pooled ORRs of the platinum-sensitive, platinum-resistant groups were 59% (95% CI 36%-81%, I2 = 61.88%), 33% (95% CI 25%-40%, I2 = 69.73%), respectively. In addition, we conducted supplementary subgroup analyses to explore the influence of FRα receptor expression levels and the number of prior treatments on treatment outcomes. The most common adverse effects were blurred vision (45.20%), nausea (40.13%), diarrhea (39.52%), fatigue (33.84%) and keratopathy (31.20%). MIRV has significant therapeutic effects in solid tumors, especially when combined with BEV. In platinum-tolerant tumors, the efficacy of MIRV is also considerable. Overall, MIRV is relatively safe in solid tumors, and adverse reactions are relatively rare and mild.

Rehim S ，Yuan S ，Wang H 《PLoS One》