A Phase I/Ii Study Of The Anti-Programmed Cell Death-1 (Pd-1) Antibody Ak105 In Patients With Relapsed Or Refractory Classic Hodgkin Lymphoma (Chl).

e19017 Background: AK105 is a humanized IgG1 mAb that blocks PD-1 binding to PD-L1 allowing T-cells to recognize and kill tumor cells. Key attributes of AK105 include antibody engineering to eliminate Fc mediated effector function, and a slower off-rate on antigen binding resulting in improved receptor occupancy. These features were designed to offer more robust biological effect and enhance anti-tumor activity of AK105. Methods: A multicenter, Phase I/II, single-arm study in relapsed/refractory cHL (NCT03722147) began in July, 2018, evaluating the safety and efficacy of AK105 administered IV q2w till disease progression (response assessed by Lugano 2014 criteria). Eligible pts had relapsed/refractory cHL after most recent therapy with progression after autologous hematopoietic stem cell transplantation, or at least 2 lines of prior chemotherapy. Enrollment for Phase I part of the study was completed, and Phase II at the RP2D of AK105 200 mg q2w is ongoing. Results: As of 1 Feb, 2019, in the Phase I part, 6 Chinese patients (pts) median age 26.5 years [19–38], female 33%, ECOG 0/1 ([67%/33%]), had received a median of 7 (3–12) doses of AK105 200mg q2w. No DLT and SAE were reported. No immune-related grade 2 (G2) or higher adverse reactions were reported. Treatment-related adverse events (TRAEs) occurred in 83% (5/6) of pts (G3 in 17% [1/6], no G4, none leading to treatment interruption or discontinuation). Most frequent TRAEs (≥2 pts) were hypothyroidism (33%, 2/6) and ALT increased (33%, 2/6). PK profile for Chinse pts is consistent with that in Caucasian pts. Of 5 evaluable heavily pretreated pts, ORR was 100% (5/5, 3 CR and 2 PR). All 3 pts achieved CR at the first tumor assessment (i.e., week 8) and remained in CR at the last assessment (i.e., week 24) prior to data cutoff. The other 2 pts achieved PR at week 8 and the responses are still ongoing. Conclusions: The reported safety profile and encouraging early antitumor activity of AK105 supports continued clinical development, which include: pivotal studies in relapsed/refractory cHL and metastatic nasopharyngeal carcinoma, phase 2/3 combination studies with chemotherapy in NSCLC and combination study with anlotinib, a multi-targeting tyrosine kinase inhibitor in hepatocellular carcinoma. Clinical trial information: NCT03722147.