An anti-TIGIT/anti–PD-1 combination approach with ociperlimab plus tislelizumab will be examined in a phase 2 study of patients with previously treated recurrent or metastatic cervical cancer.
The ongoing phase 2 AdvanTIG-202 study (NCT04693234) in patients with previously treated recurrent or metastatic cervical cancer is actively evaluating the combination of the anti-TIGIT monoclonal antibody ociperlimab (BGB-A1217) plus tislelizumab (BGB-A317), according to a poster presentation at The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer.1
The study aims to explore the efficacy and safety of tislelizumab plus ociperlimab vs tislelizumab monotherapy. Prior preclinical and trial data have shown that the dual targeting of tumors with anti-TIGIT and anti–PD-1 monoclonal antibodies produces synergistic immune cell activation and enhanced antitumor activity in this patient population.
Although the first-line standard of care for patients with recurrent or metastatic cervical cancer remains platinum-based chemotherapy with or without bevacizumab (Avastin), the treatment armamentarium in second line remains limited.2 Notably, PD-1/PD-L1 inhibitors have produced moderate efficacy rates in the patient population, leading to the induction of the AdvanTIG-202 trial.
Ociperlimab is a humanized monoclonal antibody that binds to TIGIT, blocking interactions with ligands on tumor cells. The immune checkpoint receptor TIGIT is upregulated on T Cells and natural killer cells on multiple solid tumors, which can inhibit antitumor immune responses.3
AdvanTIG-202 is a multicenter, 1:1 randomized study that has accrued approximately 167 patients 18 years of age or older with histologically or cytologically confirmed cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix who have experienced disease progression on or after at least 1 prior line of chemotherapy and are not amenable to curative treatment.
Moreover, patients are required to have: an ECOG performance status score of 1 or less; at least 1 measurable lesion per RECIST v1.1 criteria; and a life expectancy of at least 12 weeks. Patients who have had prior treatment with any PD-1/PD-L1 antibodies, checkpoint inhibitors, or other anti-TIGIT therapies will be excludes.
Additionally, patients are required to submit qualified archival tumor tissue with an associated pathology report or agree to a tumor biopsy to determine PD-L1 expression and analyze other biomarkers. Notably, patients with evaluable PD-L1 expression are eligible for the stage 2 expansion cohort to receive ociperlimab plus tislelizumab.
Stage 1 will randomize patients to receive 900 mg of intravenous (IV) ociperlimab plus 200 mg of IV tislelizumab every 3 weeks in cohort 1, or 200 mg of IV tislelizumab every 3 weeks in cohort 2. The treatment will continue until disease progression or unacceptable toxicity. Patients in cohort 1 of the stage 2 expansion will also receive 900 mg of IV ociperlimab plus 200 mg of IV tislelizumab every 3 weeks.
The primary end points of the study is overall response rate (ORR) of cohort 1 per RECIST v1.1 assessed by independent review committee (IRC), and this will be evaluated in both patients with a PD-L1 TAP score of at least 5% and all patients, regardless of PD-L1 expression. Investigator-assessed ORR for cohort 1 is a secondary end point. IRC- and investigator-assessed secondary end points for both cohorts include: ORR (cohort 2 only); duration of response; disease-control rate; progression-free survival; time to response; and clinical-benefit rate.
Other secondary end points for both cohorts include: overall survival; safety; health-related quality of life; pharmacokinetics; and immunogenicity. Additionally, biomarker status and quality of life are exploratory end points.
Tumor imaging will be performed 28 days prior to the administration of study treatment. Further imaging will be conducted every 6 weeks for the first 54 weeks of the study, then every 12 weeks thereafter.
Additional safety will be monitored through the incidence and severity of adverse events, per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, laboratory results, vital signs, ECOG performance status, and other examinations. Safety analysis will include all patients who receive at least 1 dose of study treatment.
The phase 2 study has begun enrollment and recruitment is ongoing.