I-Mab Updates Phase 1 Givastomig Data at ESMO 2024

I-Mab, a U.S.-based biotech firm, has announced encouraging top-line results from its ongoing Phase 1 clinical study of givastomig. Givastomig is a bispecific antibody targeting Claudin 18.2-positive tumor cells and activating T cells through the 4-1BB pathway in the tumor microenvironment. This study was presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain.

The Phase 1 clinical study (NCT04900818) of givastomig focuses on patients with advanced cancers, including gastric cancers such as gastroesophageal carcinoma (GEC). Givastomig, also known as TJ033721 or ABL111, has shown promising results even in tumors with low Claudin 18.2 expression levels and has maintained a favorable safety profile.

The recommended dose for Phase 2 of givastomig is set at 8-12 mg/kg. The drug has been well tolerated up to the highest doses studied. Currently, a Phase 1b study is evaluating givastomig in combination with standard-of-care treatment (nivolumab plus chemotherapy) in front-line gastric cancer patients.

Dr. Phillip Dennis, Chief Medical Officer of I-Mab, highlighted the potential of givastomig as a front-line treatment for gastric cancers. The data from ESMO 2024 indicated that givastomig demonstrated continued efficacy as a monotherapy in heavily pre-treated patients with varying levels of Claudin 18.2 expression. The Phase 1b study aims to further investigate the combination of givastomig with nivolumab and chemotherapy, with results expected in the second half of 2025.

The Phase 1 study's updated poster presentation at ESMO 2024 included data from 43 patients with advanced GEC, all confirmed to be Claudin 18.2-positive. The study evaluated doses ranging from 5 to 18 mg/kg. The objective response rate (ORR) for single-agent givastomig was 16.3%, with partial responses observed in seven patients. Notably, five of these seven patients had previously received a checkpoint inhibitor.

Stable disease was reported in 14 patients, leading to a disease control rate (DCR) of 48.8%. No dose-limiting toxicity was observed up to 15 mg/kg Q2W and 18 mg/kg Q3W, and a maximum tolerated dose was not identified. Most treatment-related adverse events were grade 1 or 2. The pharmacokinetics of givastomig exhibited a linear profile at doses of 5 mg/kg or higher, and soluble 4-1BB levels increased in a dose-dependent manner, plateauing between 8 mg/kg and 18 mg/kg.

Givastomig's favorable safety profile and single-agent activity in heavily pre-treated patients underscore its potential as a differentiated, leading therapy for gastric cancers. The ongoing Phase 1b study will continue to explore givastomig's efficacy and safety in combination with standard-of-care treatments.

Givastomig was granted Orphan Drug Designation by the U.S. FDA in March 2022 for the treatment of gastric cancer, including gastroesophageal cancer. The development program for givastomig is a global partnership between I-Mab and ABL Bio, with I-Mab taking the lead and sharing worldwide rights, excluding China and South Korea, equally with ABL Bio.

I-Mab remains focused on advancing its immunotherapy pipeline to address unmet needs in cancer treatment. The company operates globally with headquarters in Rockville, Maryland.