Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with pembrolizumab in patients with platinum-resistant ovarian cancer.

OBJECTIVE

Evaluate the efficacy and safety of mirvetuximab soravtansine-gynx (MIRV) plus pembrolizumab in dose escalation and expansion cohorts of heavily pretreated patients with platinum-resistant ovarian cancer (PROC).

METHODS

Participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease relapsed ≤6 months from last platinum-based treatment received MIRV (6 mg/kg adjusted ideal body weight) and pembrolizumab (200 mg) intravenously once every 3 weeks. Tumor FRα expression thresholds were ≥25 % (dose escalation cohort) and ≥50 % (dose expansion cohort) of cells with ≥2+ membrane staining intensity. The primary efficacy endpoint was objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety.

RESULTS

Fifty-six participants received the doublet. Median age was 62 years (range, 40-78). Twenty percent of participants had 3 prior lines of systemic treatment, 43 % had ≥4 prior lines, 43 % had prior bevacizumab exposure, and 41 % had prior PARP inhibitor exposure. Among 55 response-evaluable participants, ORR was 31 % (95 % CI, 19-45), median DOR was 8.0 months (95 % CI, 4.2-NR), and median PFS was 4.2 months (95 % CI, 2.8-5.6). Efficacy persisted in patients with multiple prior lines of treatment. Treatment-emergent adverse events were consistent with the profiles of each agent; the most common were diarrhea (all grades, 57 %; grade 3, 4 %), nausea (55 %; 5 %), and fatigue (50 %; 2 %). Treatment-emergent pneumonitis occurred in 25 % of participants, with grade ≥3 events occurring in 2 (4 %) participants.

CONCLUSIONS

MIRV plus pembrolizumab demonstrated anti-cancer efficacy and a tolerable safety profile in heavily pretreated patients with PROC. However, the efficacy benefit may be mainly attributable to MIRV alone.