Ociperlimab Plus Tislelizumab Demonstrates Antitumor Activity in PD-L1+ NSCLC

Ociperlimab (BGB-A1217), an anti-TIGIT monoclonal antibody, plus the anti–PD-1 monoclonal antibody tislelizumab (BGB-A317) induced promising efficacy in adults with treatment-naïve, metastatic, PD-L1–positive non­–small cell lung cancer (NSCLC), according to data from the dose-expansion cohort of the phase 1 AdvanTIG-105 trial (NCT04047862).¹

Rajiv Kumar, MB ChB, MD (Res), BMedSci, a medical oncologist with St George’s Cancer Care Centre in Christchurch, New Zealand, presented findings from patients in cohort 3 of the multicohort, parallel assignment trial at the 2022 IASLC World Conference on Lung Cancer.

“The combination of ociperlimab and tislelizumab demonstrated antitumor activity in patients with metastatic NSCLC and had an acceptable safety profile, with most treatment-emergent adverse effects [TEAEs] being grade 1 or 2 in severity,” he said.

At a median follow-up of 23.0 weeks (range, 3.0-61.7), the unconfirmed overall response rate (ORR) for the 39 patients evaluable for efficacy was 53.8% (95% CI, 37.2%-69.9%). For patients with PD-L1 tumor cell (TC) positivity score of 1% to 49% (n = 25), the unconfirmed ORR was 44.0% (95% CI, 24.4%-65.1%) and 71.4% (95% CI, 41.9%-91.6%) for those with PD-L1 TC 50% or greater (n = 14).

One patient in the 50% or greater subgroup had a complete response. All other responses were partial.

The median duration of response (DOR) was not evaluable (NE; 95% CI, 4.2-NE) among all treated patients and across cohorts. Further, the disease control rate (DCR) was 89.7% and the median progression-free survival (PFS) was 5.4 months (95% CI, 4.2-NE) among all patients. For those with PD-L1 expression below 50%, the median DCR was 88.0% with a median PFS of 5.2 months. In the PD-L1 at least 50% cohort the DCR was 92.9% with a median PFS of 5.6 months.

“Ociperlimab is a humanized IgG1 monoclonal antibody (mAb) designed to bind to Fc-intact TIGIT with high affinity and specificity. Tislelizumab is an anti-PD-1 mAb approved for the treatment of NSCLC in China,” Kumar explained in a poster presentation.

AdvanTIG-105 is a Phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of ociperlimab plus tislelizumab in patients with advanced, metastatic unresectable solid tumors. Investigators established the recommended phase 2 dose of 900 mg intravenous (IV) ociperlimab plus 200 mg IV tislelizumab every 3 weeks. Treatment continued until disease progression, intolerable toxicity, or withdrawal of consent.

Forty patients with patients with histologically or cytologically confirmed metastatic squamous or nonsquamous PD-L1–positive NSCLC and nonsquamous patients with EGFR/ALK/ROS1 wild-type NCLC were enrolled as of April 5, 2022.

The median patient age was 65 years and women made up 32.5% of the cohort.

The primary end point was investigator-assessed ORR per RECIST 1.1. Secondary end points included investigator-DOR, DCR per RECIST 1.1, and safety. Investigators also assessed the association between PD-L1 expression and efficacy.

The safety analysis included 40 patients, and 38 (95.0%) experienced at least 1 TEAEs and 31 (77.5%) experienced at least 1 treatment-related AE (TRAE). Eleven (27.5%) experienced grade 3 or greater TEAEs and 4 (10.0%) experienced grade 3 or greater TRAEs.

One patient died because of cerebral infarction while on study, but that was not related to the study drugs.

Ten (25.0%) patients experienced serious TEAEs and 4 (10.0%) serious TRAEs. One incident of discontinuation of each study drug because of TRAEs.

Investigators are evaluating the combination for patients with previously treated recurrent or metastatic cervical cancer in the phase 2 AdvanTIG-202 trial (NCT04693234).²

References

1. Kumar R, Kim SH, Lu S, et al. AdvanTIG-105: phase 1b dose-expansion study of ociperlimab plus tislelizumab in patients with metastatic NSCLC. Presented at: 2022 IASLC World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Poster EP08.01-073.
2. Wu L, Wang PH, Hsiao SY, et al. 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. Presented at: Society of Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer; March 18-21, 2022; Phoenix, Arizona. Accessed August 5, 2022. bit.ly/3bsyxWJ