Br J Cancer. 2025;133(2):208-215.
Multicenter phase Ib/II study of second-line durvalumab and tremelimumab in combination with paclitaxel in patients with biomarker-selected metastatic gastric cancer.
제1저자 이근욱, 장대영, 김형돈 · 교신저자 류민희, 김학균
소속 (5)
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
- Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.
- Departmentof Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- Departmentof Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. miniryu@amc.seoul.kr.
- Center for Gastric Cancer, National Cancer Center, Goyang, Republic of Korea. hkim@ncc.re.kr.
Abstract
BACKGROUND This multicenter phase Ib/II trial aimed to evaluate the safety and efficacy of combining durvalumab, tremelimumab, and paclitaxel as second-line treatment for biomarker-selected patients with metastatic gastric cancer.
METHODS In phase Ib, the standard 3 + 3 dose escalation method was used. Durvalumab and tremelimumab were administered every 4 weeks for 13 and 4 cycles, respectively, combining paclitaxel 80 mg/m2 (dose level 2) or 60 mg/m2 (dose level 1) on days 1, 8, and 15. The primary outcome for phase II was the objective response rate (ORR).
RESULTS In phase Ib (n = 7), dose level-1 was selected as the recommended phase II dose. In phase II, 48 patients were enrolled: microsatellite instability-high or deficient mismatch repair protein tumors (n = 16); EBV-positive tumors (n = 15); high tumor mutation burden ( ≥ 5/Mb) (n = 11); CD274 amplification (n = 5); and POLD1 mutation (n = 1). The ORR was 52.1%, meeting the primary endpoint. The median progression-free survival and overall survival were 5.3 and 13.1 months, respectively. The most common any-grade and grade 3-4 adverse events were anemia (41.7%) and neutropenia (10.4%), respectively.
CONCLUSIONS Durvalumab-tremelimumab with paclitaxel was tolerable and efficacious in biomarker-selected gastric cancer patients as a second-line treatment, highlighting the importance of biomarker-based approaches for immunotherapy in gastric cancer.
CLINICAL TRIAL REGISTRATION NCT03751761.
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.
Comment · 정정
Conflict of interest statement
Competing interests: Nothing directly related to this work. Outside of this work, LKW reported receiving research funding for clinical trials from MSD, AstraZeneca, Ono Pharmaceutical, Roche, Merck KGaA, BeiGene, Astellas Pharma, Amgen, Daiichi Sankyo, ALX Oncology, Leap Therapeutics, GlaxoSmithKline, Macrogenics, Taiho Pharmaceutical, Seagen, Y-BIOLOGICS, Bolt Biotherapeutics, Trishula Therapeutics, InventisBio, MedPacto, Ildong Pharmaceutical, Genome & Company, Arcus Biosciences, Elevar Therapeutics, Jazz Pharmaceuticals, TRIO Oncology, Exelixis, IgM Biosciences, Panolos Bioscience, Metafines, Wellmarker Bio, Medicenna, and Erasca. He also received consulting fees from Daiichi Sankyo, MSD, Astellas Pharma, AbbVie, and Metafines; honoraria for lectures or presentations from Sanofi/Aventis, Astellas Pharma, Bayer, Daiichi Sankyo, and Merck KGaA; and has an uncompensated role with ALX Oncology on a data safety monitoring or advisory board. YKK has a consulting or advisory role with ALX Oncology, Amgen, Blueprint Medicines, Bristol-Myers Squibb, DAEHWA Pharmaceutical, Macrogenics, Novartis, Surface Oncology, and Zymeworks. MHR received honoraria from DAEHWA Pharmaceuticals, Bristol Myers Squibb, Lilly, Ono Pharmaceuticals, MSD, Taiho Pharmaceuticals, Novartis, Daiichi Sankyo, and AstraZeneca; and served as a consultant for DAEHWA Pharmaceuticals, Bristol Myers Squibb, Lilly, and Ono Pharmaceuticals. HDK received research grants from Roche/Genentech and AstraZeneca and honoraria from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceuticals, Boryung Pharmaceuticals, MSD, Daiichi Sankyo, Astellas, Boostimmune, and MustBio. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of each participating center. All patients provided written informed consent. This study was performed in accordance with the ethical standards of the Institutional Research Committee and the latest Declaration of Helsinki.
그 밖의 정보
- 출판 형태
- Journal Article, Clinical Trial, Phase II, Multicenter Study, Clinical Trial, Phase I
- 저널
- British journal of cancer · eISSN 1532-1827
- 전자 출판
- 2025-05-21
- MeSH
- Humans · Stomach Neoplasms* / drug therapy / pathology / genetics · Paclitaxel* / administration & dosage / adverse effects · Female · Male · Antibodies, Monoclonal, Humanized / administration & dosage / adverse effects · Middle Aged · Antineoplastic Combined Chemotherapy Protocols* / therapeutic use / adverse effects / administration & dosage · Aged · Antibodies, Monoclonal / administration & dosage / adverse effects · Adult · Biomarkers, Tumor / genetics · Neoplasm Metastasis
- Substances
- tremelimumab · durvalumab · Paclitaxel · Antibodies, Monoclonal, Humanized · Antibodies, Monoclonal · Biomarkers, Tumor
- 연구비
- National Cancer Center (NCC) 24H1660 · National Cancer Center (NCC) 24H1710
- 데이터
- ClinicalTrials.gov: NCT03751761
- 참고문헌
- 41편