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

NCT04363801 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: DEK-DKK1-P205
• Study Type: interventional
• Target: 247
• Locations: 3 countries
• Sites: 48

Brief 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

Conditions

Gastric Cancer; Gastric Adenocarcinoma; GastroEsophageal Cancer

Keywords

Gastric cancer; Gastroesophageal junction; cancer; adenocarcinoma; DKK1; Tislelizumab; DKN-01

Outcome Measures

Primary Outcomes (2)

• 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.

  approximately 28 months

• 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.

  approximately 30 months

Secondary Outcomes (22)

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

  approximately 28 months

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

  approximately 28 months

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

  approximately 28 months

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

  approximately 28 months

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

  approximately 28 months

Study Arms (5)

Part A First Line Treatment

EXPERIMENTAL

Part 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.

Drug: DKN-01 300mg; Drug: DKN-01 400mg; Drug: Tislelizumab 200mg; Drug: Tislelizumab 400mg

Part B1 Second Line Treatment

EXPERIMENTAL

Part 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.

Drug: DKN-01 300mg; Drug: DKN-01 400mg

Part B2 Second Line Treatment

EXPERIMENTAL

Part 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.

Drug: DKN-01 600mg; Drug: DKN-01 400mg

Part C Control First Line Treatment

ACTIVE COMPARATOR

Part 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.

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 Treatment

EXPERIMENTAL

Part 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.

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

Interventions

DKN-01 300mg DRUG

Administered by IV infusion

Also known as: Experimental

Part A First Line Treatment; Part B1 Second Line Treatment

DKN-01 600mg DRUG

Administered by IV infusion

Also known as: Experimental

Part B2 Second Line Treatment; Part C Experimental First Line Treatment

DKN-01 400mg DRUG

Administered by IV infusion

Also known as: Experimental

Part A First Line Treatment; Part B1 Second Line Treatment; Part B2 Second Line Treatment; Part C Experimental First Line Treatment

Tislelizumab 200mg DRUG

Administered by IV infusion

Also known as: humanized IgG4 anti-PD-1 monoclonal antibody, Tevimbra

Part A First Line Treatment; Part C Control First Line Treatment; Part C Experimental First Line Treatment

Tislelizumab 400mg DRUG

Administered by IV infusion

Also known as: humanized IgG4 anti-PD-1 monoclonal antibody, Tevimbra

Part A First Line Treatment; Part C Control First Line Treatment; Part C Experimental First Line Treatment

Oxaliplatin DRUG

Administered by IV infusion

Also known as: Eloxatin

Part C Control First Line Treatment; Part C Experimental First Line Treatment

Capecitabine 1000mg/ m2 twice daily (BID) DRUG

Administered orally

Also known as: Xeloda

Part C Control First Line Treatment; Part C Experimental First Line Treatment

Leucovorin Calcium DRUG

Administered by IV infusion

Also known as: Folinic acid

Part C Control First Line Treatment; Part C Experimental First Line Treatment

Fluorouracil DRUG

Administered by IV infusion

Also known as: 5-FU

Part C Control First Line Treatment; Part C Experimental First Line Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead
• BeiGene: collaborator

Study Sites (48)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

The Angeles Clinic Research Institute - A Cedars-Sinai Affiliate

Los Angeles, California, 90025, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

Location

Northwestern University Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Pontchartrain Cancer Center

Covington, Louisiana, 70433, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Institut Fur Klinisch Onkologische Forschung Am Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Hämatologisch-Onkologische Praxis Eppendorf (HOPE)

Hamburg, 20249, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Slk-Kliniken

Heilbronn, 74078, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Caritas Klinikum Saarbrücken St. Theresia

Saarbrücken, 66113, Germany

Location

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, 13520, South Korea

Location

Korea University Ansan Hospital

Ansan-si, 15355, South Korea

Location

Hallym University Sacred Heart Hospital

Anyang, 14068, South Korea

Location

Dong-A University Hospital

Busan, 49201, South Korea

Location

National Cancer Center

Goyang, 10408, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Hanyang University Hospital

Seoul, 04763, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Boramae Hospital SNU

Seoul, 07061, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 3722, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

The Catholic University of Korea St. Mary's Hospital

Seoul, 6591, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, 16247, South Korea

Location

Related Publications (1)

• 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.

  PMID: 39432867 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasms; Adenocarcinoma

Interventions

tislelizumab; Oxaliplatin; Capecitabine; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Limitations and Caveats

The study was terminated prematurely due to lack of efficacy. Therefore, only limited efficacy analyses were performed on the primary and limited secondary efficacy endpoints. Parts A+B were initiated and completed. Part C was initiated upon completion of Parts A+B. Due to termination of the program during Part C, combined analysis for Parts A+B and C was not performed.

Results Point of Contact

• Title: Douglas Onsi / President and CEO
• Organization: Leap Therapeutics, Inc.

donsi@leaptx.com

617-218-1116

Study Officials

• Cynthia Sirard, MD

  Chief Medical Officer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 27, 2020
• Study Start: July 29, 2020
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: October 9, 2025
• Results First Posted: October 9, 2025

Record last verified: 2025-09

Locations

US (23); DE (7); KR (18)