Impact Of Dose Modifications On Ocular Adverse Events In Phase 3 Mirasol Trial Of Mirvetuximab Soravtansine-Gynx Vs Investigator’S Choice Chemotherapy In Recurrent, Folate Receptor Alpha -Positive, Platinum-Resistant Ovarian Cancer

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting FRα biomarker to deliver the DM4 potent microtubule inhibitor and lead to specific antitumor killing. MIRV is approved (US and Europe) for treatment of FRα-positive platinum-resistant ovarian cancer (PROC), supported by data in MIRASOL demonstrating statistically significant and clinically meaningful improvements in survival and antitumor response with MIRV vs chemotherapy. Most common adverse events (AEs) with MIRV were blurred vision and keratopathy, which were managed with supportive care and dose modifications and were resolvable in most patients (pts). This analysis investigated impact of dose modifications on reduction and resolvability of ocular AEs in MIRASOL.

MIRASOL (GOG 3045/ENGOT-ov55) is a global, confirmatory, open-label, randomized, controlled phase 3 trial of MIRV vs investigator’s choice chemotherapy (ICC) in pts with FRα-positive, high-grade serous PROC.

In MIRASOL, 453 pts with PROC with high FRα expression (by VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) who had 1-3 prior systemic therapies were randomized 1:1 to take MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) or ICC. Primary endpoint was progression-free survival by investigator; secondary endpoints included objective response rate, overall survival, patient-reported outcomes, safety, and duration of response. Here, a post hoc assessment of the primary analysis (data cutoff: March 6, 2023; 13.1-month median follow-up) evaluated dose reductions due to treatment-emergent ocular events (TEOEs) in all randomized pts receiving ≥1 MIRV dose (safety population, n=218). TEOEs were evaluated by grouped preferred term per NCI-CTCAE (v5.0).

Of 218 pts,122 (56%) had any-grade TEOEs, most commonly (n [%]), blurred vision (98 [45%]), keratopathy (80 [37%]), dry eye (61 [28%]), and cataract (34 [16%]). TEOEs completely or partially resolved in 113/122 (93%) pts. Of 43/122 (35%) pts with TEOEs that led to dose reductions: most frequent events (n [%]) were blurred vision (31/43 [72%]) and/or keratopathy (22/43 [51%]), and 21/43 (49%) had complete resolution and 22/43 (51%) had partial improvement of ≥1 TEOE; of 42 pts with available data, 30/42 (71%) had 1 reduction and 12/42 (29%) had 2 reductions. Median (IQR) time to onset of first TEOE that led to dose reduction was 53 (35–134) days. Recurrent TEOEs after initial dose reduction were mostly grade 1 or 2, with no grade ≥4 events.

In pts in MIRASOL treated with MIRV, TEOEs were primarily low-grade and completely or partially resolved in 93%. In pts with TEOEs that led to dose reduction, most had 1 reduction with none undergoing >2 reductions, and nearly all had complete or partial resolution of ≥1 TEOE. No grade ≥4 TEOEs recurred after dose reduction. Four pts (2%) total in the MIRV arm discontinued treatment due to ocular AEs. By characterizing ocular AEs with MIRV and demonstrating their manageability through dose reductions, these data highlight the importance of ophthalmic care in pts undergoing MIRV therapy and enable the ophthalmologist to collaborate with oncologists to mitigate ocular AEs with dose modification strategies supporting treatment continuity.