Evidence map›Paper›PMID 35790315›Full record

Trial reportJournal for immunotherapy of cancer2022

Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.

Minsuk Kwon, Gahyun Kim, Ryul Kim, Kyu-Tae Kim, Seung Tae Kim, Simon Smith, Peter G S Mortimer, Jung Yong Hong, Arsene-Bienvenu Loembé, Itziar Irurzun-Arana and 6 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03780608 (Phase II Study of AZD6738 in Combination With Durvalumab), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03780608 phase2unknown statusnot on this map

Phase II Study of AZD6738 in Combination With Durvalumab (MEDI4736), in Patients With Metastatic Solid Tumor as Salvage Treatment

TypeinterventionalSponsorSamsung Medical CenterRan2019 to 2023Enrolled61ConditionsGastric Adenocarcinoma, Malignant MelanomaArmsAZD6738, Durvalumab
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. Pooled it
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  18. A General Metallaphotoredox Platform forJournal of the American Chemical Society · 2025
    Article
  19. Review
  20. ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment.International journal of molecular sciences · 2025
    Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Minsuk Kwon *Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Gahyun Kim *Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
Ryul KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Kyu-Tae KimDepartment of Physiology, Ajou University, Suwon, Republic of Korea.
Seung Tae KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Simon SmithOncology R&D, AstraZeneca, Cambridge, UK.
Peter G S MortimerOncology R&D, AstraZeneca, Cambridge, UK.
Jung Yong HongDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Arsene-Bienvenu LoembéOncology R&D, AstraZeneca, Cambridge, UK.
Itziar Irurzun-AranaOncology R&D, AstraZeneca, Cambridge, UK.
Loumpiana KoulaiOncology R&D, AstraZeneca, Cambridge, UK.
Kyoung-Mee KimDepartment of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-1162-9205
Won Ki KangDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Emma DeanOncology R&D, AstraZeneca, Cambridge, UK.
Woong-Yang ParkSamsung Genome Institute, Samsung Medical Center, Gangnam-gu, Republic of Korea.
Jeeyun LeeDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea jyunlee@skku.edu.
Samsung Medical Center · KRAstraZeneca (United Kingdom) · GBSamsung (South Korea) · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTargeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.

methodsThis phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15-28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients.

resultsAmong 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p<0.001). During the study treatment, upregulation of the innate immune response by cytosolic DNA, activation of intratumoral lymphocytes, and expansion of circulating tumor-reactive CD8 +T cell clones were identified in responders. Enrichment of the tumor vasculature signature was associated with treatment resistance.

conclusionsCeralasertib plus durvalumab has promising antitumor activity, with durable responses in patients with refractory AGC. Thus, a biomarker-driven trial is required.

trial registrationNCT03780608.

Indexed as

Antibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsProtein Kinase InhibitorsStomach NeoplasmsAntineoplastic AgentsAntineoplastic Agents, ImmunologicalAtaxia Telangiectasia Mutated ProteinsHumansIndolesMorpholinesPyrimidinesSulfonamidesSulfoxidesAntibodies, MonoclonalAntineoplastic AgentsAntineoplastic Agents, ImmunologicalAtaxia Telangiectasia Mutated ProteinsATM protein, humanATR protein, humanceralasertibdurvalumabIndolesMorpholinesProtein Kinase InhibitorsPyrimidinesSulfonamidesSulfoxidesclinical trials, phase II as topicgastrointestinal neoplasmsgenome instabilityprogrammed cell death 1 receptor

Identifiers

PMID35790315
PMCPMC9258491
OpenAlexW4283827539

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.