105P - A single-arm, phase II, multicenter study of iparomlimab (QL1604) in patients (pts) with unresectable/metastatic deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) solid tumors

Background

PD-1 blockade has brought impressive response rate in pts with dMMR/MSI-H solid tumors compared with chemotherapy. QL1604, a novel anti-PD-1 antibody, has shown good safety and preliminary anti-tumor activity in advanced solid tumors in the phase I study.

Methods

This single-arm, phase II study (NCT04326829) evaluated the efficacy and safety of QL1604 in pts with unresectable or metastatic dMMR/MSI-H solid tumors from 38 clinical sites across China. Pts received QL1604 (200 mg, iv, Q3W; 3 mg/kg for pts with body weight <40 kg, Q3W), until disease progression, intolerance, withdrawal of consent, or up to 2 years (whichever occurred first). The primary endpoint was objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST 1.1.

Results

From Jun 19, 2020 to Jan 12, 2023, 120 pts with dMMR/MSI-H solid tumors were enrolled, of whom 80 (66.7%) pts had colorectal cancer (CRC), 18 (15.0%) pts had gastric cancer, and 22 (18.3%) had other solid tumors. A total of 97.5% pts had stage IV disease at study entry, and the median prior therapy lines was 2.0 (range, 0-6). With median follow-up of 13.59 mo (range, 0.5–35.3 mo), the ORR and DCR per IRRC were 55/120 (45.8%; 95% CI: 36.7%–55.2%) and 93/120 (77.5%, 95% CI: 69.0%–84.6%), respectively, with 11 (9.2%) complete response (CR) and 44 (36.7%) partial response. In the CRC subgroup, the ORR and DCR per IRRC were 34/80 (42.5%, 95% CI: 31.5%–54.1%) and 62/80 (77.5%, 95% CI: 66.8%–86.1%), respectively. Overall, median duration of response (DoR) was not reached, with 6-mo and 12-mo DoR rates of 100% (95% CI: NE–NE) and 97.4% (95% CI: 83.2%–99.6%), respectively. Median progression-free survival and median overall survival were not reached. TEAEs of any grade occurred in 117 (97.5%) pts. The most frequent treatment-related adverse events (TRAEs) of any grade and grade ≥3 TRAEs were both anemia, with incidence of 25.8% and 5.0%, respectively. No QL1604-related death occurred.

Conclusions

QL1604 showed promising efficacy with high response rate and durable response and tolerable toxicity in pts with dMMR/MSI-H solid tumors.

Clinical trial identification

NCT04326829.

Editorial acknowledgement

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd.

Funding

Qilu Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.