AdvanTIG-202: A phase 2 study investigating anti-TIGIT monoclonal antibody ociperlimab plus anti-PD-1 monoclonal antibody tislelizumab in patients with previously treated recurrent or metastatic cervical cancer.

Abstract

TPS5595 Background: Women with recurrent/metastatic cervical cancer represent a poor prognostic group with high unmet clinical needs. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) is a co-inhibitory, immune checkpoint receptor expressed on immune cells and upregulated on T-cells and natural killer cells in multiple solid tumors, inhibiting anticancer immune responses. Ociperlimab (BGB-A1217) is a novel, humanized, monoclonal antibody that binds TIGIT with high specificity and affinity, blocking the interaction with its ligands on tumor cells. Tislelizumab is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-202 is a Phase 2, randomized, multicenter, open-label study (NCT04693234). Approximately 167 pts with cervical squamous cell or adenosquamous carcinoma or adenocarcinoma, recruited from 100 centers, whose disease progressed on or after ≥ 1 prior line of chemotherapy for recurrent/metastatic disease will be included in this 2-Part study. In Part 1, approximately 80 pts will be randomized (1:1) to either ociperlimab 900 mg intravenously (IV) in combination with tislelizumab 200 mg IV every 3 weeks (Q3W) (Arm 1), or tislelizumab monotherapy 200 mg IV Q3W (Arm 2), until disease progression, unacceptable toxicity, or withdrawal of consent. In Part 2, Arm 1 will be expanded by approximately 87 additional pts whose tumors are evaluable for PD-L1 expression. The primary endpoint is overall response rate (ORR) (RECIST v1.1) assessed by Independent Review Committee (IRC) in Arm 1. Secondary endpoints are investigator-assessed ORR in Arm 2, IRC-assessed and investigator-assessed ORR in Arm 1, IRC-assessed and investigator-assessed duration of response, progression-free survival, time to response, disease control rate, clinical benefit rate and overall survival, cancer-specific health-related quality of life (HRQoL), safety, pharmacokinetics and immunogenicity in Arms 1 and 2. Exploratory endpoints are generic HRQoL and the association of biomarkers with patient prognosis, response or resistance. Clinical trial information: NCT04693234.

Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy

“…This drug binds to the extracellular domain of human TIGIT with high affinity and blocks the interaction between TIGIT and its ligand CD155 or CD112 while preserving intact Fc segment function, which is essential for its antitumor activity; it exerted synergistic antitumor effects when combined with anti-PD-1/PD-L1 mAbs [ 176 ]. The results of Phase I clinical trials designed to evaluate ociperlimab combined with tislelizumab (anti-PD-1 mAb) were first reported at ASCO in 2021, and they confirmed that ociperlimab combined with tislelizumab was well tolerated; moreover, antitumor efficacy was observed in patients with advanced solid tumors (NCT04693234) [ 177 ]. In June 2023, a Phase III clinical trial evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC without an operational driver mutation was initiated (NCT05791097).…”

Targeting TIGIT for cancer immunotherapy: recent advances and future directions

“…The findings were reported to be all-dose-tolerable in advanced solid tumors with promising antitumor activity [ 192 ]. On top of that, this combination treatment strategy was also conducted in several other clinical studies, including AdvanTIG-202 (phase II) [ 193 ], AdvanTIG-203 (NCT04732494, phase II) [ 194 ], AdvanTIG-206 (NCT04948697, phase II) [ 195 ], and AdvanTIG-302 (NCT04746924, phase III) [ 196 ].…”

Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody

“…In a phase I study, the combination of tislelizumab and ociperlimab resulted in an ORR of 4.2% (1/24) and a DCR of 41.7% (10/24) in previously treated patients, without causing grade ≥4 treatmentrelated adverse events (TRAEs). 39 Besides, several trials investigating the effect of this combination are ongoing, [66][67][68][69] the results of which are worth expecting.…”