Safety and efficacy of QLS31905 in patients with advanced solid tumors: Updated data from phase 1 study.

2527 Background: QLS31905 is a Claudin18.2/CD3 bispecific antibody. Here we report the updated data of a phase 1 study of QLS31905. Methods: This multicenter phase 1 trial (NCT05278832) recruited patients (pts) with advanced solid tumors who had progressive disease or were intolerable to or inapplicable of standard therapy. In dose-escalation stage adopting accelerated titration and interval 3+3 design, pts regardless of Claudin18.2 status were administered QLS31905 via intravenous infusion in 11 sequential single doses (0.5, 1.5, 5, 15, 45, 100, 200, 350, 500, 800, 1200 μg/kg qw or q2w) with priming dose from 350 μg/kg. In dose-expansion stage, Claudin18.2-positive (≥1% tumor cells) pts were recruited. The primary endpoint was dose limiting toxicities (DLT) and maximum tolerated dose (MTD) in dose-escalation stage, and was objective response rate (ORR) in dose-expansion stage. Results: As of Jul 26, 2024, 31 pts were included from 0.5 μg/kg qw to 1200 μg/kg q2w in dose-escalation stage, and 48 pts were included in five cohorts (100~200 μg/kg qw and 350~800 μg/kg q2w) in dose-expansion stage. The 1200 μg/kg q2w cohort is ongoing. There were 43 (54.4%) pts with gastric or gastroesophageal junction (G/GEJ) cancer and 26 (32.9%) with pancreatic adenocarcinoma (PAC). Over half of (61.8%) pts had received ≥2 lines of prior treatment. No DLT occurred. MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 79 (100%) pts, of whom 34 (43.04%) were ≥grade 3. The most common ≥grade 3 TRAEs (≥3%) were lymphocyte count decreased (21.5%), γ-glutamyl transferase increased (3.8%), neutrophil count decreased (3.8%), cytokine release syndrome (CRS [3.8%]), and anemia (3.8%). CRS occurred in 17 (21.52%) pts including two pts with grade 3 and one with grade 4, and all recovered. Two pts (2.53%) discontinued treatment due to TRAEs of abdominal pain and CRS, respectively. No TRAE leading to death occurred. In 33 Claudin18.2-positive pts in 350~1200 μg/kg q2w cohorts, six pts (three with G/GEJ cancer and three with PAC) had partial response. ORR was 18.18% (95% confidence interval [CI]: 6.98%, 35.46%), disease control rate (DCR) was 87.88% (95% CI: 71.80%, 96.60%), median progression-free survival (PFS) was 4.21 months (95% CI: 2.99, 5.55), and median overall survival (OS) was 9.53 months (95% CI: 7.69, not evaluable). Among the Claudin18.2-positive pts in 350~1200 μg/kg q2w cohorts, ORR, DCR, median PFS, median OS was 15.79%, 89.47%, 4.40 months, 9.20 months in 19 pts with G/GEJ cancer, and was 25.00%, 91.67%, 3.94 months, not reached in 12 pts with PAC, respectively. QLS31905 exposure was generally linear with the administered dosage. There was no tendency of accumulation after multiple administrations. Conclusions: QLS31905 was safe and tolerable, and showed encouraging efficacy in Claudin18.2-positive pts with gastrointestinal tumors. QLS31905 is worthy of further exploration in combined therapy in phase 2 trials. Clinical trial information: NCT05278832 .