Evidence map›Paper›PMID 40640119›Full record

Trial reportNature communications2025

DKN-01 and tislelizumab as second-line therapy in DKK1-high gastroesophageal adenocarcinoma: DisTinGuish trial part B.

Keun-Wook Lee, Devalingam Mahalingam, Byoung Yong Shim, In-Ho Kim, Do-Youn Oh, Hope Uronis, Sun Jin Sym, Mohamad Sonbol, Khaldoun Almhanna, Mohamedtaki A Tejani and 8 more

Erratum issued Registry-linked trialAbstract readMulticenter StudyClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04363801 (A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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.

NCT04363801 phase2terminatednot on this map

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (DisTinGuish)

TypeinterventionalSponsorLeap Therapeutics, Inc.Ran2020 to 2025Enrolled247ConditionsGastric Cancer, Gastric Adenocarcinoma, GastroEsophageal CancerArmsDKN-01 300mg, DKN-01 600mg, DKN-01 400mg, Tislelizumab 200mg, Tislelizumab 400mg
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Keun-Wook LeeDepartment of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. imdoctor@snu.ac.kr.
Devalingam MahalingamRobert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-2979-9894
Byoung Yong ShimThe Catholic University of Korea St. Vincent's Hospital, Suwon, Korea.ORCID http://orcid.org/0000-0001-6473-786X
In-Ho KimSeoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Do-Youn OhSeoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Hope UronisDuke University Medical Center, Durham, NC, USA.
Sun Jin SymGachon University Gil Medical Center, Incheon, Korea.
Mohamad SonbolMayo Clinic Hospital, Phoenix, AZ, USA.
Khaldoun AlmhannaRhode Island Hospital, Brown University Medical Center, Providence, RI, USA.
Mohamedtaki A TejaniAdvent Health Cancer Institute, Orlando, FL, USA.
Beodeul KangCHA Bundang Medical Center, Seongnam, Korea.
Michael H KageyLeap Therapeutics, Cambridge, MA, USA.
Melissa StilianLeap Therapeutics, Cambridge, MA, USA.
Calvin JiaLeap Therapeutics, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8732-6035
Cynthia A SirardLeap Therapeutics, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4856-4457
Rachel AlturaLeap Therapeutics, Cambridge, MA, USA.
Jaffer A AjaniMD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9946-0629
Samuel J KlempnerDepartment of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. sklempner@mgb.org.ORCID http://orcid.org/0000-0002-4062-0808

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Biomarker-enriched, chemotherapy-free treatments for patients with advanced gastric and gastroesophageal junction cancer have not been widely explored. In this multicenter, phase 2 trial (NCT04363801), we evaluated the efficacy and safety of second-line doublet immunotherapy, combining DKN-01, an immunomodulating antibody targeting Dickkopf-related protein 1 (DKK1), with the anti-programmed cell death-1 (PD1) antibody, tislelizumab in patients with advanced gastric/gastroesophageal junction cancer and elevated tumor DKK1 expression, a putative predictive biomarker for DKN-01. Here we report part B (second line cohort) of the larger DisTinGuish trial. The primary endpoint was safety and tolerability, with secondary endpoints including objective response rate (ORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR). The trial met the prespecified primary endpoint. In the safety population (n = 52), 21 (40.4%) patients reported at least 1 DKN-01-related adverse event, most of which were low-grade, with fatigue (15.4%) and nausea (9.6%) being most common. The ORR was 21.7% in the overall population (n = 46) and 31.8% in the programmed death-ligand 1 (PD-L1) ≥ 5% population. The median OS was 8.2 months, median PFS 1.4 months, and DCR rate 34.8% in the overall population. Although exploratory, the results of this trial compare favorably against second-line benchmarks of Keynote-061 and RAINBOW and support the safety and tolerability of DKN-01 combined with tislelizumab.

Indexed as

AdenocarcinomaAntibodies, Monoclonal, HumanizedEsophageal NeoplasmsIntercellular Signaling Peptides and ProteinsStomach NeoplasmsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorEsophagogastric JunctionFemaleHumansMaleMiddle AgedTreatment OutcomeAntibodies, Monoclonal, HumanizedBiomarkers, TumorDKK1 protein, humanIntercellular Signaling Peptides and Proteinstislelizumab

Identifiers

PMID40640119
PMCPMC12246393

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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.