Evidence map›Paper›PMID 39432867›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2025

DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.

Samuel J Klempner, Mohamad Bassam Sonbol, Zev A Wainberg, Hope Elizabeth Uronis, Vi K Chiu, Aaron James Scott, Syma Iqbal, Mohamedtaki Abdulaziz Tejani, Vincent Chung, Melissa C Stilian and 7 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

33 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. CD74Journal of gastrointestinal cancer · 2026
    Article
  7. Review
  8. Review
  9. Review
  10. DKK1 expression associates with tertiary lymphoid structure maturity in non-small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review
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

17 authors.

Samuel J KlempnerDepartment of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA.ORCID 0000-0002-4062-0808
Mohamad Bassam SonbolMayo Clinic, Phoenix, AZ.ORCID 0000-0002-6931-242X
Zev A WainbergUniversity of California Los Angeles Medical Center, Los Angeles, CA.ORCID 0000-0002-7142-1246
Hope Elizabeth UronisDuke University Medical Center, Durham, NC.ORCID 0009-0000-1565-1939
Vi K ChiuThe Angeles Clinic & Research Institute, a Cedars-Sinai affiliate, Los Angeles, CA.
Aaron James ScottUniversity of Arizona Cancer Center, Tucson, AZ.ORCID 0000-0002-0301-3072
Syma IqbalUniversity of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA.ORCID 0000-0002-5010-5922
Mohamedtaki Abdulaziz TejaniAdventHealth Cancer Institute, Orlando, FL.
Vincent ChungCity of Hope National Medical Center, Duarte, CA.ORCID 0000-0001-9475-808X
Melissa C StilianLeap Therapeutics, Inc, Cambridge, MA.
Mathis ThomaLeap Therapeutics, Inc, Cambridge, MA.
Ying ZhangLeap Therapeutics, Inc, Cambridge, MA.
Michael H KageyLeap Therapeutics, Inc, Cambridge, MA.
Jason BaumLeap Therapeutics, Inc, Cambridge, MA.
Cynthia A SirardLeap Therapeutics, Inc, Cambridge, MA.ORCID 0000-0003-4856-4457
Rachel A AlturaLeap Therapeutics, Inc, Cambridge, MA.
Jaffer A AjaniMD Anderson Cancer Center, Houston, TX.ORCID 0000-0001-9946-0629

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

purposeThe outcomes of anti-PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study. PATIENTS AND

methodsPatients had untreated human epidermal growth factor receptor 2-negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m

resultsBetween September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.

conclusionDKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).

Indexed as

AdenocarcinomaAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsEsophageal NeoplasmsEsophagogastric JunctionStomach NeoplasmsAdultAgedCapecitabineFemaleHumansMaleMiddle AgedOxaliplatinProgression-Free SurvivalAntibodies, Monoclonal, HumanizedCapecitabineOxaliplatintislelizumab

Identifiers

PMID39432867
PMCPMC11771358

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.