Efficacy and safety of cafelkibart (LM-108), an anti-CCR8 monoclonal antibody, in combination with anti-PD-1 therapy in patients with pancreatic cancer: Results from phase 1/2 studies.
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Le résumé fourni par la source
4010 Background: Targeting tumor-infiltrating Tregs presents a promising strategy to overcome resistance to immunotherapy in cancer treatment. LM-108 is a novel Fc-optimized anti-CCR8 monoclonal antibody designed to selectively deplete tumor-infiltrating Tregs while sparing peripheral Tregs. This pooled analysis of two phase 1/2 trials assesses the efficacy and safety of LM-108 in combination with anti-PD-1 therapy in patients with pancreatic cancer. Methods: Eligible patients (pts) with pancreatic cancer who had progressed on or after at least one prior line of systemic therapy were included. Treatment regimens included LM-108 at doses of 3 mg/kg Q3W, 3 mg/kg Q2W, 10 mg/kg Q3W, or 10 mg/kg Q2W, in combination with pembrolizumab (400 mg Q6W) or toripalimab (240 mg Q3W). The primary endpoint was ORR. Secondary endpoints were DCR, PFS, OS, DoR, safety, and biomarkers analysis. Data cutoff: December 2, 2024. Results: A total of 80 pts (median age: 63 years; 58.8% male) from China and Australia were treated. Of these, 48 pts had progressed on or after 1 prior line of therapy, and 32 pts had ≥2 lines. Eighteen pts (22.5%) had prior anti-PD-1 therapy, and 52 pts (65.0%) had liver metastases at baseline. TRAEs were reported in 76 pts (95.0%). Common TRAEs (≥25%) included increased AST, increased ALT, anemia, rash, pyrexia, decreased platelet count and increased conjugated bilirubin. Grade ≥3 TRAEs occurred in 42 pts (52.5%), the most common events (≥5%) were lipase elevation (7.5%), increased ALT (6.3%), increased AST (5.0%), immune-mediated enterocolitis (5.0%), hypokalemia (5.0%), and rash (5.0%). Median follow-up was 10.48 months (95% CI 7.20-12.65). Among 74 efficacy-evaluable pts, ORR was 20.3% (95% CI 11.8-31.2%) and DCR was 62.2% (95% CI 50.1-73.2%). Median DoR was 5.49 months (95% CI 3.02-8.87), PFS was 3.12 months (95% CI 1.61-4.86), and OS was 10.02 months (95% CI 6.41-13.11). Among 45 pts who had progressed on or after one prior line of therapy, ORR was 24.4% (95% CI 12.9-39.5%) and DCR was 71.1% (95% CI 55.7-83.6%), with a median DoR of 6.93 months (95% CI 3.02-NA), PFS of 4.86 months (95% CI 2.79-6.90), and OS not reached. The 12-month OS rate was 51.6% (95% CI 31.4-68.5%). Among these, 9 pts with high CCR8 expression (7 with baseline liver metastases) showed ORR of 33.3% (95% CI 7.5-70.1%) and DCR of 77.8% (95% CI 40.0-97.2%). Median PFS was 6.90 months (95% CI 1.22-NA), and OS was 9.15 months (95% CI 3.61-NA). Conclusions: LM-108 in combination with anti-PD-1 therapy demonstrated encouraging antitumor activity and a manageable safety profile in patients with pancreatic cancer who had progressed on or after prior systemic therapies. These findings support further investigation of LM-108 in combination with anti-PD-1 therapy as a potential treatment option for pancreatic cancer. Clinical trial information: NCT05199753 ; NCT05518045 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Efficacy and safety of cafelkibart (LM-108), an anti-CCR8 monoclonal antibody, in combination with anti-PD-1 therapy in patients with pancreatic cancer: Results from phase 1/2 studies.
- 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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Fudan University Department of Pancreatic Surgery pays non établi dans la noticeUniversité ou école supérieure
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Zhongshan Hospital pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of Henan University of Science and Technology Oncology department pays non établi dans la noticeÉtablissement de santé
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Zhejiang Provincial People's Hospital pays non établi dans la noticeÉtablissement de santé
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Wuhan University Gastrointestional Oncology (Chemoradiotherapy) Department pays non établi dans la noticeUniversité ou école supérieure
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Zhongnan Hospital of Wuhan University pays non établi dans la noticeÉtablissement de santé
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Heze Municipal Hospital pays non établi dans la noticeÉtablissement de santé
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Nanyang Medical College pays non établi dans la noticeÉtablissement de santé
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Linear Clinical Research pays non établi dans la noticeStructure de recherche
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Zhejiang Cancer Hospital Department of Thoracic Oncology pays non établi dans la noticeÉtablissement de santé
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) — Peking University, Peking University Cancer Hospital et Department of Pancreatic Surgery — Fudan University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.