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Abstract
VP4-2024: First-in-class PD-1/IL-2 bispecific antibody fusion protein IBI363 in patients (pts) with advanced solid tumors: First-in-human phase I study
1 Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, China
2 VIP Ward & Department of Clinical Nutrition & Cancer Bio-Immunotherapy Center, Fujian Cancer Hospital, Fuzhou, China
3 Abdominal Medicine, Hubei Cancer Hospital, Wuhan, China
4 First Chest Radiotherapy Department, Hunan Cancer Hospital, Changsha, China
5 Phase I Clinical Research Center, Shandong First Medical University Affiliated Cancer Hospital/Shandong Cancer Hospital/Shandong Cancer Prevention and Treatment Research Institute, Jinan, China
6 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
7 Medical Oncology, Anhui Provincial Hospital, Heifei, China
8 Oncology, The First Hospital of Jilin University, Changchun, China
9 Second Department of Thoracic Tumors, Peking University Cancer Hospital, Beijing, China
10 Department of Melanoma Oncology, The Third People's Hospital of Zhengzhou, Zhengzhou, China
11 Gyn-Surgical Oncology, Fujian Provincial Cancer Hospital, Fuzhou, China
12 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
13 Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
14 Colorectal Surgery, The Sixth Affiliated Hospital of SYSU, Guangzhou, China
15 Department of Thoracic Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College - National Cancer Center, Cancer Hospital, Beijing, China
16 Department of Head and Neck and Rare Oncology, Chinese Academy of Sciences Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
17 Clinical Development, Innovent Biologics, Inc., Beijing, China
Published: June 13, 2024
DOI: https://doi.org/10.1016/j.annonc.2024.05.540 Download PDF
Background
IBI363 has great potential to address unmet clinical need of immunotherapy (IO) resistant and cold tumors by blocking PD-1 checkpoint and cis-activating α-bias IL-2 to rejuvenate exhausted tumor-specific T cells.
Methods
Eligible pts failed or intolerant to standard therapy were enrolled. IBI363 was intravenously administered with accelerated titration (0.2/2/10/30 μg/kg QW) and Bayesian optimal interval design (0.1/0.3/0.6/1 mg/kg QW). Further dose optimization was evaluated at 0.3/0.6/1 mg/kg Q2W and 0.6/1/1.5/2/3 mg/kg Q3W. Endpoints were safety and efficacy per RECIST v1.1.
Results
As of Feb 23, 2024, 326 pts were enrolled (males: 60.7%, ECOG PS 1: 63.3%) with 168 pts at 1 mg/kg, 99 pts below and 59 pts above 1 mg/kg. In dose escalation (n = 22), DLTs occurred in 1 pt at 0.1 mg/kg QW (G4 neutrophil count decreased) and 1 pt at 1 mg/kg QW (G3 arrhythmia). TRAEs occurred in 287 pts (88.0%, with 20.9% ≥G3). Most common TRAEs were arthralgia (33.4%, with 3.1% ≥G3) and anemia (22.7%, with 2.5% ≥G3). TRAEs led to IBI363 discontinuation and death in 9 (3.0%) and 2 (0.7%) pts. In total, 272 pts (≥0.1 mg/kg, 77 with non-small cell lung cancer [NSCLC], 67 with melanoma, 79 with colorectal cancer and 49 with other tumors) had at least 1 post-baseline tumor assessment. Overall ORR was 17.6% (95% CI: 13.3-22.7) and DCR was 57.0% (95% CI: 50.9-62.9). DoR was immature with 8 (16.7%) of 48 responders had events. IO treated pts (n = 185) had ORR of 17.8% (95% CI: 12.6-24.1) and DCR of 62.2% (95% CI: 54.8-69.2). In NSCLC (n = 77, prior tx ≥2L: 79.2%, with 8 had EGFR mutations), ORR was 22.1% (95% CI: 13.4-33.0) and DCR was 67.5% (95% CI: 55.9-77.8). Among them, IO treated pts (n = 72) had ORR of 22.2% (95% CI: 13.3-33.6) and DCR of 68.1% (95% CI: 56.0-78.6). In squamous NSCLC (n = 36, prior tx ≥ 2L: 69.4%, with 35 IO treated, 1 EGFR positive by IHC), ORR was 30.6% (95%CI: 16.3-48.1), DCR was 75.0% (95%CI: 57.8-87.9) and median PFS was 5.5 months (95% CI: 4.0-NC) with 14 (38.9%) pts had events. All squamous NSCLC pts at 3 mg/kg Q3W had partial response (n=4). In mucosal melanoma (n = 25), ORR was 32.0% (95% CI: 14.9-53.5) and DCR was 68.0% (95% CI: 46.5-85.1).
Conclusions
IBI363 was well tolerated in all pts with encouraging efficacy in advanced NSCLC and melanoma.
Clinical trial identification
NCT05460767.
Legal entity responsible for the study
Innovent Biologics (Suzhou) Co., Ltd.
Funding
Innovent Biologics (Suzhou) Co., Ltd.
Disclosure
H. Zhou: Other, Personal and Institutional, Full or part-time Employment: Innovent Biologics (Suzhou) Co., Ltd.
All other authors have declared no conflicts of interest.