Safety and efficacy of QLS31905 in patients with advanced solid tumors: Updated data from phase 1 study.
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Le résumé fourni par la source
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 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Safety and efficacy of QLS31905 in patients with advanced solid tumors: Updated data from phase 1 study.
- Date Crossref
- 01/06/2025
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Peking University Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) pays non établi dans la noticeUniversité ou école supérieure
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Peking University Cancer Hospital pays non établi dans la noticeÉtablissement de santé
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Anhui Medical University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Anhui Medical University pays non établi dans la noticeÉtablissement de santé
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Shandong First Medical University Phase I Clinical Trial Ward pays non établi dans la noticeUniversité ou école supérieure
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Zhengzhou University Department of Medical Oncology pays non établi dans la noticeUniversité ou école supérieure
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Henan Cancer Hospital pays non établi dans la noticeÉtablissement de santé
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Qingdao University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
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Affiliated Hospital of Qingdao University pays non établi dans la noticeÉtablissement de santé
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Harbin Medical University Department of Gastrointestinal Medical Oncology pays non établi dans la noticeUniversité ou école supérieure
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Third Affiliated Hospital of Harbin Medical University pays non établi dans la noticeÉtablissement de santé
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Jilin University Cancer Center pays non établi dans la noticeUniversité ou école supérieure
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) — Peking University, Peking University Cancer Hospital et Department of Oncology — Anhui Medical University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.