Objectives

Mirvetuximab soravtansine (MIRV) is a first-in-class ADC comprising a folate receptor-α (FRα)-binding antibody, cleavable linker, and maytansinoid DM4 payload. As part of the phase 1b/2 trial (NCT02606305), efficacy, safety, and tolerability of MIRV and bevacizumab (BEV) were evaluated in patients with recurrent FRα-positive ovarian cancer (OC) measured by immunohistochemistry (PS2+ ≥25%).

Methods

Patients received MIRV (6 mg/kg, adjusted ideal body weight) and BEV (15 mg/kg) intravenously on Day 1 of a 3-week cycle. Primary endpoint was confirmed ORR assessed by RECIST v1.1. Safety and tolerability of MIRV + BEV were secondary endpoints.

Results

Patients enrolled (N=126; median age 62 years) were heavily pretreated (46%, ≥3 prior therapies) and 75% were platinum resistant. Prior taxane, BEV, or PARPi treatment occurred in 98%, 52%, and 27%, respectively. Low, medium, and high FRα expression in patient tumors was 10%, 40%, and 49%, respectively.

MIRV demonstrated anti-tumor activity in the entire cohort (ORR 44%, mDOR 11.8 months, mPFS 8.2 months), with ORR of 58% in BEV-naïve and 32% in prior BEV (Table 1).

Grade 3+ treatment emergent adverse events (TEAEs) were low; common TEAEs (Grade 3+, all grade) included diarrhea (2%, 67%), nausea (2%, 59%), blurred vision (1%, 56%), fatigue (5%, 53%), and hypertension (17%, 33%).

Conclusions

MIRV and BEV demonstrated anti-tumor activity, regardless of prior BEV treatment, and should be considered in FRα-positive recurrent OC. A randomized phase 3 trial (GLORIOSA) will evaluate MIRV and BEV in the maintenance setting in patients with FRα-high platinum-sensitive OC.

Objectives

In ATHENA–MONO (NCT03522246), progression-free survival (PFS) improved with first-line rucaparib maintenance treatment vs placebo in patients with advanced ovarian cancer (OC), regardless of molecular characteristics (median PFS: 20.2 vs 9.2 months, log-rank P<0.0001; hazard ratio: 0.52; 95% CI: 0.40–0.68). Patients with or without high-risk clinical characteristics for disease progression were enrolled; in this subgroup analysis, we investigated whether all patients benefited from rucaparib first-line maintenance treatment, including those with more favorable baseline prognostic factors.

Methods

Patients with high-grade, FIGO stage III–IV OC who completed cytoreductive surgery and 4–8 cycles of first-line platinum-doublet chemotherapy with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Investigator-assessed PFS was evaluated in subgroups based on FIGO stage, timing of surgery, and residual disease status post-chemotherapy.

Results

As of Mar 23, 2022 (data cutoff), 427 and 111 patients were randomized to rucaparib monotherapy or placebo. Most patients had FIGO stage III disease (75%); approximately half underwent primary surgery (49%), and most had no residual disease (75%). In the intent-to-treat population, PFS improved with rucaparib vs placebo across all subgroups based on FIGO stage, timing of surgery, and residual disease (Table).

Conclusions

In the intent-to-treat population, first-line rucaparib maintenance treatment improved PFS vs placebo across subgroups regardless of timing of surgery or prognostic disease characteristics such as FIGO stage or residual disease. These results confirm rucaparib as a new effective maintenance treatment for OC patients with or without high-risk factors for progression at baseline, irrespective of molecular characteristics.