Abstract CT180: Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) and coformulation of vibo/pembro in ovarian cancer naive to PD-1/PD-L1 inhibitors
Authors: Perets Ruth , Gutierrez Martin , Rha Sun Young , Taylor Sarah , Stein Brian , Jimeno Antonio , Winer Ira , Chen Diana , Keenan Tanya , Rajasagi Mohini , Lala Mallika , Healy Jane , Shapira-Frommer Ronnie 
Published: June 2022

Abstract
Background: The anti-TIGIT antibody vibo in combination with pembro has shown promising antitumor activity in anti-PD-1/PD-L1-naive NSCLC. In the ongoing phase 1 trial (NCT02964013), we evaluated the safety and efficacy of these drugs given in combination (vibo + pembro) or as a coformulation (vibo/pembro) for the treatment of ovarian cancer naive to PD-1/PD-L1 inhibitors.
Methods: Patients had locally advanced unresectable or metastatic ovarian cancer naive to PD-1/PD-L1 inhibitors that progressed after ≥1 line of therapy, including platinum therapy. Patients were nonrandomly assigned to receive vibo (200 mg IV Q3W) + pembro (200 mg IV Q3W) or as the coformulation (vibo/pembro) at the same dose for ≤35 cycles (~2 years) or until disease progression (PD), toxicity, or patient withdrawal. Primary end points were safety and tolerability. Secondary and exploratory end points included PK, objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) by investigator review per RECIST v1.1. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1 or when CPS was missing, as a tumor proportion score of ≥1% or as a mononuclear immune cell density score of ≥2.
Results: Of 61 patients enrolled, 21 received vibo + pembro, and 40 received vibo/pembro. Median age was 58 years; 48% of patients had ECOG performance status 1, 15% had BRCA1 and/or BRCA2 mutations, 87% received ≥2 lines of prior therapy (66%, bevacizumab; 41%, PARP inhibitor), and 74% had platinum-resistant disease (PD &lt;6 months after platinum). PD-L1 status was positive in 21 patients, negative in 31 patients, and unknown in 9 patients. Median follow-up was 13 months (range, 9-15). Treatment-related adverse events (TRAEs) occurred in 79% of all patients; 13% were grade 3 or 4. No deaths due to TRAEs were reported. The most common TRAEs (≥20%) were fatigue (23%), pruritus (23%), and rash (20%). PK exposure was similar between treatment groups. ORR was 8% (95% CI, 3-18) in all patients and 24% (95% CI, 8-47) in patients with PD-L1-positive tumors. Median DOR was 19 months (range, 4-19). The disease control rate at 6 months was 11% (95% CI, 5-22) in all patients and 24% (95% CI, 8-47) in patients with PD-L1-positive tumors. Median PFS was 2 months (95% CI, 2-2) in all patients and 2 months (95% CI, 2-8) in patients with PD-L1-positive tumors.
Conclusions: Safety and PK were comparable with vibo + pembro combination and the vibo/pembro coformulation in patients with platinum-resistant locally advanced unresectable or metastatic ovarian cancer naive to PD-1/PD-L1 inhibitors. Antitumor activity was equivalent between the combination and coformulation, with responses limited to PD-L1-positive tumors. Vibo/pembro coformulation may offer a safe and convenient treatment option in these patients; further investigations of antitumor activity by PD-L1 status are needed.
Citation Format: Ruth Perets, Martin Gutierrez, Sun Young Rha, Sarah Taylor, Brian Stein, Antonio Jimeno, Ira Winer, Diana Chen, Tanya Keenan, Mohini Rajasagi, Mallika Lala, Jane Healy, Ronnie Shapira-Frommer. Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) and coformulation of vibo/pembro in ovarian cancer naive to PD-1/PD-L1 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT180.