Abstract CT129: A multicohort, open-label, phase 2 basket study of the coformulation of vibostolimab with pembrolizumab, with or without other anticancer therapies, in select solid tumors
Authors: Lugowska Iwona , Rojas Carlos , Gonzalez Alejandro Falcon , Cortijo Lucia Gonzalez , Hsu Chih-Hung , Yen Chia-Jui , Rha Sun Young , Yonemori Kan , Li Daneng , Geva Ravit , Salman Pamela , Ruiz Eduardo Yanez , Liu Qi , Keenan Tanya , Healy Jane , Kwiatkowski Mariusz 
Published: June 2022

Background: T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is coexpressed with PD-1 on both CD4+ and CD8+ T cells in tumors. Preclinical models and early clinical data have shown enhanced antitumor activity when an anti-TIGIT antibody is co-administered with an anti-PD-1 antibody. The efficacy and safety of a novel coformulation of the anti-TIGIT antibody vibostolimab and the anti-PD-1 antibody pembrolizumab (vibostolimab/pembrolizumab), alone or in combination with other anticancer therapies, will be investigated in select advanced solid tumors in a multicohort, open-label, phase 2 basket trial (NCT05007106).

Trial Design: Key eligibility criteria are histologically or cytologically confirmed advanced (locally recurrent unresectable or metastatic) solid tumor naive to anti-PD-1/PD-L1 therapy (Table 1). Patients will be assigned to treatment randomly (cohort A1) or nonrandomly (cohorts A2-G) by tumor type and biomarker status (Table 1). All patients will be treated until disease progression, unacceptable toxicity, patient/physician decision to withdraw, or 35 cycles of vibostolimab/pembrolizumab or pembrolizumab alone. Primary end points are objective response rate (all cohorts) and progression-free survival (PFS; cohort A1) per RECIST v1.1 by blinded independent central review (cohort A1) or investigator (cohorts A2-G). Secondary end points include PFS per RECIST v1.1 assessed by the investigator (cohorts A2-G), quality of life (cohort A1), and duration of response, overall survival, and safety (all cohorts). Enrollment is ongoing.

Table 1. Patient Population and Treatment by Cohort Cohort Patient Population Treatmenta A1b PD-L1-positive (CPS ≥1) cervical cancer that progressed on ≥1 line of therapy Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV Pembrolizumab 200 mg Q3W IV A2 PD-L1-negative (CPS &lt;1) cervical cancer that progressed on ≥1 line of therapy Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV B1 dMMR endometrial cancer that progressed after 1 prior systemic, platinum-based chemotherapy Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV B2 pMMR endometrial cancer that progressed after 1 prior systemic, platinum-based chemotherapy Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV + lenvatinib 20 mg QD PO C PD-L1-positive (CPS ≥1) head and neck squamous cell carcinoma (previously untreated) Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV D Biliary tract cancer that progressed after 1 prior systemic therapy Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV E Esophageal cancer (previously untreated) Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV + 5-FU 800 mg/m2/day on days 1-5 Q3W IV + cisplatin 80 mg/m2 Q3W IV for ≤6 cycles F Triple-negative breast cancer (previously untreated) Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV + paclitaxel 90 mg/m2 on days 1, 8, and 15 Q4W IV G Hepatocellular carcinoma (previously untreated) Vibostolimab 200 mg/pembrolizumab 200 mg Q3W IV + lenvatinib 12 mg/8 mg QD PO 5-FU, fluorouracil; CPS, combined positive score; dMRR, mismatch repair-deficient; IV, intravenously; pMRR, mismatch repair-proficient; PO, orally; Q3W, every 3 weeks; Q4W, every 4 weeks; QD, once daily. aAll treatments are ≤35 cycles unless otherwise indicated. bPatients in cohort A1 will be randomly assigned 1:1 to receive one of the 2 treatments; analysis will be stratified by prior bevacizumab use.

Citation Format: Iwona Lugowska, Carlos Rojas, Alejandro Falcon Gonzalez, Lucia Gonzalez Cortijo, Chih-Hung Hsu, Chia-Jui Yen, Sun Young Rha, Kan Yonemori, Daneng Li, Ravit Geva, Pamela Salman, Eduardo Yanez Ruiz, Qi Liu, Tanya Keenan, Jane Healy, Mariusz Kwiatkowski. A multicohort, open-label, phase 2 basket study of the coformulation of vibostolimab with pembrolizumab, with or without other anticancer therapies, in select solid tumors [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 CT129.