ABL111 gains FDA accelerated approval pathway as phase 2 gastric cancer trial begins
ABL111 received FDA agreement on an accelerated approval pathway for metastatic gastric cancer as the first patient was dosed in a global phase 2 trial. The companies said ORR will support accelerated approval and phase 2 is evaluating ABL111 with nivolumab and mFOLFOX6.
ABL111 for metastatic gastric cancer has received agreement on an accelerated approval pathway from the U.S. Food and Drug Administration, while dosing has begun for the first patient in a global phase 2 trial of the drug in combination with nivolumab and mFOLFOX6. ABL Bio and partner NovaBridge Biosciences said the FDA meeting was based on positive data from a phase 1b trial, and the companies plan to evaluate about 180 patients who are Claudin 18.2-positive and PD-L1-positive.
Following a Type B meeting with the FDA, NovaBridge received written meeting minutes containing agreement on the accelerated approval process for ABL111. ABL Bio and NovaBridge agreed to use objective response rate (ORR) as the primary endpoint for ABL111's accelerated approval, and the target for initiating the phase 3 registration trial for accelerated approval application is the fourth quarter of this year. The trial design will be finalized through additional discussions with the FDA.
The phase 2 trial will evaluate ABL111 in combination with the PD-1 inhibitor nivolumab and the chemotherapy regimen mFOLFOX6 as a first-line treatment for patients with metastatic gastric cancer. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate, overall survival (OS), duration of response (DoR), and disease control rate (DCR).
ABL111 is a bispecific antibody that simultaneously targets Claudin 18.2 and 4-1BB. It is a pipeline product utilizing ABL Bio's 4-1BB-based bispecific antibody platform, Grabody-T.
In the phase 1b trial, the ORR for the ABL111 combination therapy at 8 mg/kg was 77 percent (20 of 26 patients), and at 12 mg/kg was 73 percent (19 of 26). The ABL111 combination therapy demonstrated consistent responses regardless of patients' PD-L1 and Claudin 18.2 expression levels. Its safety profile was also similar to that of the current standard first-line therapy, with overall acceptable tolerability. The median progression-free survival was 16.9 months.