A phase Ia/b trial of ARX788 combined with toripalimab for HER2-low advanced breast cancer (ABC) and other HER2-expressing solid tumors.

e13159 Background: ARX788 has been proved with superior PFS compared with a combination of capecitabine and lapatinib in the randomized phase Ⅱ/Ⅲ study for HER2-positive ABC (Ambrx, 2023). Here we report the preliminary safety and efficacy of ARX788 plus toripalimab in HER2-low ABC and other HER2-expressing solid tumors. Methods: This was a phase Ⅰ study conducted in China. Eligible patients were HER2-low (IHC2+ and FISH- or IHC1+) ABC or HER2-expressing (IHC 2+ or 3+) solid tumors. Dose exploration with ARX788 is 1.3, 1.5mg/kg, IV, Q3W plus toripalimab 240mg, IV, Q3W. Primary endpoint was safety and RP2D of Ⅰa and efficacy of Ⅰb. Results: Totally, 12 patients were enrolled in phase Ⅰa, 10 patients were diagnosed with ABC, 1 was diagnosed with BTC and 1 was CRC. 6 patients each were treated with 1.3 and 1.5mg/kg. No DLTs were observed. 12 patients (100%) experienced ≥1 ADRs. The most common (≥20%) ADRs were AST increased (75%), platelet count decreased (75%), alopecia (41.67%), white blood cell count decreased (25%), ALT increased (25%), dry eye (25%), interstitial lung disease (25%) and neutrophil count decreased (25%). 1.5mg/kg dose level showed a slightly higher incidence in hematologic toxicities, interstitial lung disease and alopecia. Grade 3 ADRs occurred in 8 patients (66.67%) with equal incidence of the 2 dose levels, those were ocular events (41.7%, 2 of each level), interstitial lung disease (8.3%, 1 of 1.5mg/kg), platelet count decreased (8.3%, 1 of 1.5mg/kg), jaundice (8.3%, 1 of 1.3mg/kg) and immune-mediated myocarditis (8.3%, 1 of 1.3mg/kg). No grade 4 or 5 ADRs occurred. All ADRs were manageable and have recovered. ORR was 41.7% in 12 patients, with 33.3% and 50% in 1.3 and 1.5mg/kg dose level. In 10 patients with ABC, ORR was 50%, with 40% and 60% in each level. DCR was 83.33% and 100%, respectively. Thus, 1.5mg/kg was determined as RP2D and phase Ⅰb is ongoing with HER2-low ABC patients. Conclusions: ARX788 with 1.5mg/kg combined with toripalimab was shown acceptable safety profile with promising efficacy, no significant increase in adverse reactions or serious unexpected immune-related adverse reactions compared with ARX788 monotherapy, which supports further evaluation for HER2-low ABC in a larger sample in Ⅰb trial. Clinical trial information: CTR20222247.