IMM01 plus tislelizumab in patients with advanced solid tumors and lymphoma: An open-label, multicenter, phase 1b/2 dose escalation and expansion study (IMM01-04).
Authors: Song Zhengbo , Tong Xu , Zhang Yan , Zhu Hui , Zhao Yanqiu , Yu Xiaoqing , Ai Xinghao , Zong Zhenzhen , Zhao Xiwen , Gao Siman , Lu Qiying , Tian Wenzhi , Lu Shun 
Published: June 2023

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Background: IMM01, a recombinant SIRPα-Fc fusion protein, can activate macrophages to enhance anti-tumor activity by blocking CD47-SIRPα interaction. Based on preclinical results, IMM01 showed unique property of weak human erythrocyte conjugation. IMM01 plus tislelizumab has the potential to augment both innate and adaptive anti-tumor immune responses. Methods: This study included the phase 1b dose escalation part and the phase 2 dose expansion part. The dose escalation part was conducted with a standard 3+3 design to evaluate the safety, MTD/RP2D and anti-tumor activity in patients with advanced solid tumors. IMM01 (1.0, 1.5, 2.0 mg/kg) was administered once a week and tislelizumab (200mg) was administered once every 3 weeks. The results of the dose escalation part were reported here. Results: As of 26 Dec 2022, 14 pts were enrolled in the dose escalation part, including 5 NSCLC, 2 SCLC, 2 ESCC, 2 CRC, 1 HCC, 1 melanoma and 1 cervical carcinoma. Median age was 61 years (range 49-70). Median of prior therapies was 4 (range 1-10), and 13 pts (92.9%) received previous anti PD-1/L1 treatment. Treatment-related adverse events (TRAEs) occurred in 14 pts (100.0%) to date. Most TRAEs were grade 1-2. The most common TRAEs (≥10%) of all grades were anaemia (85.7%), platelet count decreased (28.6%), asthenia (28.6%), white blood cell count decreased (21.4%), lymphocyte count decreased (21.4%), IRR (21.4%), proteinuria (21.4%), gamma-glutamyltransferase increased (14.3%), white blood cell count increased (14.3%), blood creatine phosphokinase MB increased (14.3%), neutrophil count decreased (14.3%), neutrophil count increased (14.3%), hypoalbuminaemia (14.3%) and hyponatraemia (14.3%). The Grade 3-4 TRAEs were lymphocyte count decreased (21.4%), white blood cell count decreased (14.3%), platelet count decreased (14.3%), blood creatine phosphokinase MB increased (7.1%), blood pressure increased (7.1%) and anaemia (7.1%). No DLT occurred. No TRAE leading to treatment discontinuation was reported. 2 pts (14.3%) had treatment related SAE (2 platelet count decreased), they recovered without platelet transfusion and no bleeding occurred. In 14 pts, 1 pt had confirmed PR and 3 pts had SD. One heavily pre-treated NSCLC pt in the 2.0 mg/kg dose cohort had confirmed PR at Week 12, who was resistant to anti PD-1. One NSCLC pt in 1.5 mg/kg dose cohort and 2 pts (1 SCLC, 1 CRC) in 2.0 mg/kg dose cohort had SD. The treatments of these four pts are ongoing. Conclusions: Up to 2mg/kg IMM01 plus tislelizumab is well tolerated. The RP2D of IMM01 was determined as 2mg/kg, this was the highest IMM01 dose evaluated in human as a single agent. IMM01 plus tislelizumab showed preliminarily anti-tumor activity in patients with advanced solid tumors. The dose expansion part in advanced solid tumors and lymphoma is ongoing. Clinical trial information: chictr20220791 .