PF469 TISLELIZUMAB (BGB‐A317) FOR RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA: UPDATED FOLLOW‐UP EFFICACY AND SAFETY RESULTS FROM A PHASE 2 STUDY
Authors: Y. Song, Q. Gao, H. Zhang, L. Fan, J. Zhou, D. Zou, W. Li, H. Yang, T. Liu, Q. Wang, F. Lv, H. Guo, L. Yang, R. Elstrom, J. Huang, W. Novotny, V. Wei, J. Zhu
Journal: HemaSphere (2019)

Background: Programmed cell death protein 1 (PD‐1) inhibitors have broadened therapeutic options in relapsed/refractory classic Hodgkin Lymphoma (cHL). Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for PD‐1. Tislelizumab was engineered to minimize binding to FcɤR on macrophages, thereby decreasing antibody‐dependent phagocytosis, a potential mechanism of T‐cell clearance and resistance to anti–PD‐1 therapy. Aims: The primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) using the Lugano criteria. Secondary endpoints included progression‐free survival (PFS), duration of response (DOR), rate of complete response (CRR), time to response (TTR) assessed by IRC, and safety and tolerability. Methods: This is an ongoing, single‐arm, multicenter phase 2 study (ClinicalTrials.gov: NCT03209973) of tislelizumab given at 200 mg intravenously every 3 weeks until disease progression (PD) or unacceptable toxicity. Patients with relapsed/refractory cHL were eligible if they: failed to achieve a response or progressed after autologous stem cell transplant (ASCT), or: received ≥2 lines of prior systemic chemotherapy for cHL and were ineligible for ASCT. Results: Seventy patients from 11 centers in China were enrolled and treated; patient characteristics are shown in the table below. As of data cutoff date (July 23, 2018), the median follow‐up was 9.8 months (range, 3.4–14.7 mos). Fifty‐three patients (75.7%) remained on treatment; 17 patients (24.2%) discontinued (11 for PD; 4 for adverse events [AEs]; 1 withdrew consent; 1 due to pregnancy). The ORR was 87.1% and the CRR was 62.9% by IRC. The median TTR by IRC was12.0 weeks (range, 8.9–42.1). The median PFS was not reached and estimated 9‐month PFS rate was 74.5%. The median DOR was not reached. The most frequently reported AEs were pyrexia (54.3%), hypothyroidism (32.9%), increased weight (30.0%), upper respiratory tract infection (30.0%), cough (17.1%) and pruritus (17.1%). Grade ≥3 AEs reported in ≥2 patients were upper respiratory tract infection (2.9%) and pneumonitis (2.9%). Immune‐related AEs were reported in 27 patients (38.6%); grade ≥3 in 6 patients (8.6%): pneumonitis (interstitial lung disease, organizing pneumonia, pneumonitis, n = 3); skin adverse reactions (erythema nodosum), nephritis (focal segmental glomerulosclerosis), and musculoskeletal (increased creatine phosphokinase) (each n = 1). No fatal AEs were reported. AEs led to treatment discontinuation in 4 patients (5.7%): pneumonitis (n = 2), organizing pneumonia, and focal segmental glomerulosclerosis (n = 1 each). One patient died on study due to PD. Summary/Conclusion: Updated results of this study further demonstrated the substantial therapeutic activity of tislelizumab in patients with heavily pre‐treated R/R cHL, as shown by a high rate of durable deep responses. The treatment of tislelizumab was well tolerated in patients with R/R cHL. image