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AzTrials

Gastric CancerPhase 2DisTinGuishNCT04363801

A Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy in Patients With Gastric or Gastroesophageal Cancer

A Phase 2 study testing DKN-01 300mg, DKN-01 600mg and DKN-01 400mg in people with Gastric Cancer and Gastric Adenocarcinoma, run by Leap Therapeutics, Inc. at 48 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DKN-01 300mg, DKN-01 600mg and DKN-01 400mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
247 participants
Where
48 sitesin 3 countries
Study dates
29 Jul 2020to 31 Mar 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A \& C:
  • No previous therapy for cancer. Patients may have received prior neoadjuvant or adjuvant therapy as long it was completed without disease recurrence for at least 6 months since last treatment.
  • Part B Only:
  • Disease progression during first-line therapy or within 4 months after the last dose of first-line therapy.
  • Documentation of elevated Dickkopf-1 (DKK1) messenger ribonucleic acid (mRNA) expression from a fresh tumor biopsy or a biopsy obtained within the 6 months of screening.
  • Part C Only:
Show all 17Show fewer
  • Documentation of programmed cell death protein ligand-1 (PD-L1) combined positive score (CPS) by immunohistochemistry (IHC) and DKK1 mRNA expression in tumor cells by ISH from a fresh tumor biopsy (preferred) or archived tumor biopsy specimen conducted in a Sponsor designated central laboratory.
  • General:
  • Able to provide written informed consent prior to any study-specific procedures.
  • Age ≥18 years on the day of signing the informed consent (exception: ≥19 years in the Republic of Korea).
  • Confirmed diagnosis of gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma.
  • One or more tumors measurable on radiographic imaging as defined by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1.
  • Tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred] or archived specimen).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 within 7 days of first dose of study drug
  • Acceptable liver, renal, hematologic, and coagulation function
  • Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug.
  • Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for at least 6 months after the last dose of study drugs.

Who cannot join

  • Part A \& C Only:
  • Diagnosis of HER2-positive G/GEJ adenocarcinoma.
  • Unable to swallow capsules or disease significantly affected gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction (for those receiving CAPOX in Part C).
  • Prior therapy with an anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody.
  • Part B Only:
  • Major surgery or chemotherapy within 21 days of first dose of study drug.
Show all 36Show fewer
  • General:
  • Squamous cell or undifferentiated or other histological type of gastric cancer.
  • Prior therapy with an anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or co-inhibitory checkpoint pathways in any treatment setting (including adjuvant/neoadjuvant) or prior therapy with an anti-DKK1 agent.
  • Patients with active autoimmune diseases or history of autoimmune diseases that may relapse.
  • Any condition that required treatment with steroids or any other immune suppressive drugs within 14 days prior to first dose of study drug.
  • Active leptomeningeal disease or uncontrolled brain metastases.
  • Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
  • Uncontrolled diabetes or >Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥Grade 3 hypoalbuminemia within 14 days before first dose of study drug.
  • Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to first dose of study drug.
  • Clinically significant anorexia within 7 days prior to first dose of study drug.
  • History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases.
  • Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
  • Prior allogeneic stem cell transplantation or organ transplantation.
  • History of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment.
  • Known dihydropyrimidine dehydrogenase deficiency.
  • New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  • Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
  • Known to be human immunodeficiency virus (HIV) positive.
  • Serious nonmalignant disease
  • History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and clinically significant.
  • Known osteoblastic bony metastasis.
  • History of gastrointestinal perforation and/or fistulae within 6 months prior to first dose of study drug.
  • Major surgery 28 days prior to study entry.
  • Serious psychiatric or medical conditions that could interfere with treatment.
  • Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for Adverse Events (AEs) not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
  • Administration of a live vaccine within 28 days before first dose of study drug.
  • Active substance abuse.
  • Pregnant or nursing.
  • Concurrent participation in another therapeutic clinical study.
  • Prior radiation therapy within 14 days prior to study entry.

Trial locations and contacts

48 sites in 3 countries.

48 sites in 3 countries

United States23 sites
  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • Pontchartrain Cancer Center

    Covington, Louisiana, 70433

  • City of Hope

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • The Angeles Clinic Research Institute - A Cedars-Sinai Affiliate

    Los Angeles, California, 90025

  • University of Southern California

    Los Angeles, California, 90033

  • UCLA

    Los Angeles, California, 90095

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • Chao Family Comprehensive Cancer Center, University of California, Irvine

    Orange, California, 92868

  • AdventHealth Cancer Institute

    Orlando, Florida, 32804

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Cancer Center

    Phoenix, Arizona, 85054

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • University of California San Francisco

    San Francisco, California, 94158

  • University of Arizona

    Tucson, Arizona, 85724

Other trials in United States

South Korea18 sites
  • Korea University Ansan Hospital

    Ansan-si, 15355

  • Hallym University Sacred Heart Hospital

    Anyang, 14068

  • Dong-A University Hospital

    Busan, 49201

  • National Cancer Center

    Goyang, 10408

  • Gachon University Gil Medical Center

    Incheon, 21565

  • Inha University Hospital

    Incheon, 22332

  • Seoul National University Bundang Hospital

    Seongnam, 13620

  • CHA Bundang Medical Center

    Seongnam-si, Gyeonggi-do, 13520

  • Korea University Anam Hospital

    Seoul, 02841

  • Hanyang University Hospital

    Seoul, 04763

  • Asan Medical Center

    Seoul, 05505

  • Boramae Hospital SNU

    Seoul, 07061

  • Korea University Guro Hospital

    Seoul, 08308

  • Seoul National University Hospital

    Seoul, 3080

  • Severance Hospital, Yonsei University Health System

    Seoul, 3722

  • Samsung Medical Center

    Seoul, 6351

  • The Catholic University of Korea St. Mary's Hospital

    Seoul, 6591

  • The Catholic University of Korea St. Vincent's Hospital

    Suwon, 16247

Other trials in South Korea

Germany7 sites
  • Charité Universitätsmedizin Berlin

    Berlin, 13353

  • Institut Fur Klinisch Onkologische Forschung Am Krankenhaus Nordwest

    Frankfurt, 60488

  • Hämatologisch-Onkologische Praxis Eppendorf (HOPE)

    Hamburg, 20249

  • Universitatsklinikum Heidelberg

    Heidelberg, 69120

  • Slk-Kliniken

    Heilbronn, 74078

  • Studienzentrum Onkologie Ravensburg

    Ravensburg, 88212

  • Caritas Klinikum Saarbrücken St. Theresia

    Saarbrücken, 66113

Other trials in Germany

About this study

Official title: 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)

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

Read the detailed description

This is a Phase 2 open-label, multicenter study to be conducted concurrently in 3 Parts (Parts A, B, and C). Approximately 232 patients aged 18 years or older with inoperable, histologically confirmed locally advanced or metastatic Gastric or Gastroesophageal Junction (G/GEJ) adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy will be enrolled in the study. Part A and B are designed to evaluate safety, tolerability, and efficacy of the combination therapy of intravenous (IV) DKN-01 and tislelizumab ± CAPOX in G/GEJ adenocarcinoma patients. Treatment continues in repeating 21-day cycles until patient meets criteria for discontinuation or is no longer deriving clinical benefit. Two doses of DKN-01 will be evaluated in Part B (Part B1 and Part B2). Part C is the open-label, randomized, controlled, 2-arm portion of the study to evaluate the efficacy and safety of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) ± DKN-01 in adult patients with inoperable, histologically confirmed locally advanced or metastatic G/GEJ adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy. Approximately 160 patients will be randomized in a 1:1 ratio to receive either DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6) (n=80) or tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) (n=80).

Being tested
DKN-01 300mg, DKN-01 600mg, DKN-01 400mg, Tislelizumab 200mg, Tislelizumab 400mg
Keywords
Gastric cancer, Gastroesophageal junction, cancer, adenocarcinoma, DKK1, Tislelizumab, DKN-01
Medical subject headings
Stomach Neoplasms, Neoplasms, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DKN-01 300mgDrug

    Also called Experimental

    Administered by IV infusion

  • DKN-01 600mgDrug

    Also called Experimental

    Administered by IV infusion

  • DKN-01 400mgDrug

    Also called Experimental

    Administered by IV infusion

  • Tislelizumab 200mgDrug

    Also called humanized IgG4 anti-PD-1 monoclonal antibody, Tevimbra

    Administered by IV infusion

  • Tislelizumab 400mgDrug

    Also called humanized IgG4 anti-PD-1 monoclonal antibody, Tevimbra

    Administered by IV infusion

  • OxaliplatinDrug

    Also called Eloxatin

    Administered by IV infusion

  • Capecitabine 1000mg/ m2 twice daily (BID)Drug

    Also called Xeloda

    Administered orally

  • Leucovorin CalciumDrug

    Also called Folinic acid

    Administered by IV infusion

  • FluorouracilDrug

    Also called 5-FU

    Administered by IV infusion

Study groups in NCT04363801
Study groupRoleWhat they receive
Part A First Line TreatmentExperimentalPart A patients will receive IV DKN-01 (300 mg) on Days 1 and 15, IV tislelizumab (200 mg) on Day 1, IV oxaliplatin (130 mg/m2) on Day 1, and oral capecitabine (1000 mg/m2 twice daily [BID]) on Days 1-15 of each 21-day cycle. Part A is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
Receives: Drug: DKN-01 300mg; Drug: DKN-01 400mg; Drug: Tislelizumab 200mg; Drug: Tislelizumab 400mg
Part B1 Second Line TreatmentExperimentalPart B patients will receive IV DKN-01 (300 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±Human Epidermal growth factor Receptor 2 [HER2] therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy.
Receives: Drug: DKN-01 300mg; Drug: DKN-01 400mg
Part B2 Second Line TreatmentExperimentalPart B patients will receive IV DKN-01 (600 mg) on Days 1 and 15 and IV tislelizumab (200 mg) on Day 1 of each 21-day cycle. Patients enrolled in Part B are required to have DKK1-high (H-score ≥ 35) G/GEJ adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy.
Receives: Drug: DKN-01 600mg; Drug: DKN-01 400mg
Part C Control First Line TreatmentActive comparatorPart C control patients will receive only tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
Receives: Drug: Tislelizumab 200mg; Drug: Tislelizumab 400mg; Drug: Oxaliplatin; Drug: Capecitabine 1000mg/ m2 twice daily (BID); Drug: Leucovorin Calcium; Drug: Fluorouracil
Part C Experimental First Line TreatmentExperimentalPart C experimental patients will receive DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6). Part C is restricted to patients who have not had prior systemic therapy for locally advanced or metastatic disease. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months.
Receives: Drug: DKN-01 600mg; Drug: DKN-01 400mg; Drug: Tislelizumab 200mg; Drug: Tislelizumab 400mg; Drug: Oxaliplatin; Drug: Capecitabine 1000mg/ m2 twice daily (BID); Drug: Leucovorin Calcium; Drug: Fluorouracil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients

    Number of subjects with adverse drug reactions and toxicities as assessed by CTCAE v5.0 CAPOX (capecitabine + oxaliplatin) in patients with inoperable, locally advanced or metastatic G/GEJ adenocarcinoma.

    Measured: approximately 28 months

  2. Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy

    PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first.

    Measured: approximately 30 months

Secondary outcomes (22)
  1. Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy

    Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) through radiological assessment of tumor response, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Investigators were urged to have the same radiographic imaging modality used throughout the study for each subject (at baseline and at subsequent assessments) in order to provide uniformity of radiographic assessments.

    Measured: approximately 28 months

  2. Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

    Measured: approximately 28 months

  3. Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier.

    Measured: approximately 28 months

  4. Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    DoCR is defined as the time from initial complete response (CR) until radiographically documented progressive disease or death due to any cause, whichever is first.

    Measured: approximately 28 months

  5. Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.

    Measured: approximately 28 months

  6. Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.

    Measured: approximately 28 months

  7. Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    DoCB is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks.

    Measured: approximately 28 months

  8. Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    Durable clinical benefit (DCB) is defined as the proportion of patients presenting a Duration of clinical benefit (DoCB) for ≥180 days from initiation of DKN-01. Patients who have a best overall response of PD or those with clinical benefit lasting <180 days are not included.

    Measured: approximately 28 months

  9. Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy

    DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1.

    Measured: approximately 28 months

  10. Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier.

    Measured: approximately 28 months

  11. Part B: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    Duration of complete response (DoCR) is defined as the time from initial CR until radiographically documented progressive disease or death due to any cause, whichever is first. No patients had a complete response (CR); therefore, the DoCR was not applicable.

    Measured: approximately 28 months

  12. Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.

    Measured: approximately 28 months

  13. Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.

    Measured: approximately 28 months

  14. Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    Duration of clinical benefit (DoCB) is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks.

    Measured: approximately 28 months

  15. Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    DCB rate is defined as the proportion of patients presenting a DoCB (Duration of clinical benefit) for ≥ 180 days from initiation of DKN-01, Patients who have a best overall response of PD or those with clinical benefit lasting <180 days will not be included.

    Measured: approximately 28 months

  16. Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy

    DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1.

    Measured: approximately 28 months

  17. Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.

    Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX

    Measured: approximately 30 months

  18. Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.

    The duration of response (DoR) is defined only for responders (patients with a BOR of CR or PR) at the time from initial response (CR or PR) until radiographically documented progressive disease or death due to any cause, whichever is earlier. For ORR patient without PD or death, DoR is censored at the most recent tumor assessment before the data cutoff or study withdrawal, whichever occurs first.

    Measured: approximately 30 months

  19. Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.

    Overall survival (OS) OS is defined as the time from the date of randomization to death due to any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored at the date the patient was last known to be alive (i.e., date of last contact). Patients lacking data beyond the day of randomization is censored at the date of randomization (i.e., OS duration of 1 day).

    Measured: approximately 30 months

  20. Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy.

    PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first.

    Measured: approximately 30 months

  21. Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy.

    Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Risk difference (RD)(%) or ORR: Positive RD implies the exposure is associated with a higher probability of the outcome occurring. Negative RD indicates the exposure is associated with a lower probability of the outcome occurring.

    Measured: approximately 30 months

  22. Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms.

    To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each treatment arm: Control (tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) and Experimental (DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6))

    Measured: approximately 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2020
  2. Study start29 Jul 2020
  3. Primary completion31 Mar 2025
  4. Study completion31 Mar 2025

Why it stopped: experimental treatment will not be more efficacious than its comparator in the primary endpoint of PFS

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
247 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04363801
Sponsor's protocol ID
DEK-DKK1-P205
Acronym
DisTinGuish
Status last verified
Sep 2025
First submitted
23 Apr 2020
Last updated
9 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Rha SY, Ryu MH, Kim JG, Xu S, Xu Y, Lee KW. Comparative efficacy of tislelizumab + FOLFOX or CAPOX for gastric/gastroesophageal junction adenocarcinoma: an exploratory matching-adjusted indirect comparison. Curr Med Res Opin. 2026 May;42(5):1031-1041. doi: 10.1080/03007995.2026.2686048. Epub 2026 Jun 29.

    PubMed 42371751
  • Yu J, Mehta R. Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257036. doi: 10.6004/jnccn.2025.7036.

    PubMed 40341124
  • Klempner SJ, Sonbol MB, Wainberg ZA, Uronis HE, Chiu VK, Scott AJ, Iqbal S, Tejani MA, Chung V, Stilian MC, Thoma M, Zhang Y, Kagey MH, Baum J, Sirard CA, Altura RA, Ajani JA. DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish. J Clin Oncol. 2025 Jan 20;43(3):339-349. doi: 10.1200/JCO.24.00410. Epub 2024 Oct 21.

    PubMed 39432867

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DKN-01 300mg, DKN-01 600mg and DKN-01 400mg in people with Gastric Cancer and Gastric Adenocarcinoma, run by Leap Therapeutics, Inc. at 48 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, South Korea, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients (time frame: approximately 28 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04363801, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.

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