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

• ClinicalTrials.gov Identifier: NCT04363801
• Recruitment Status: Recruiting
• First Posted: April 27, 2020
• Last Update Posted: June 5, 2023
• Sponsor: Leap Therapeutics, Inc.
• Collaborator: BeiGene
• Information provided by (Responsible Party): Leap Therapeutics, Inc.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Gastric Cancer; Gastric Adenocarcinoma; GastroEsophageal Cancer	Drug: DKN-01 300mg; Drug: DKN-01 600mg; Drug: DKN-01 400mg; Drug: Tislelizumab 200mg; Drug: Tislelizumab 400mg; Drug: Oxaliplatin; Drug: Capecitabine 1000mg/ m2 BID; Drug: Leucovorin Calcium; Drug: Fluorouracil	Phase 2

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 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: July 29, 2020
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A First Line Treatment; 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; Administered by IV infusion; Drug: DKN-01 400mg; Administered by IV infusion; Drug: Tislelizumab 200mg; Administered by IV infusion; Drug: Tislelizumab 400mg; Administered by IV infusion
Experimental: Part B1 Second Line Treatment; 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; ±HER2 therapy if applicable). Patients may have received prior neoadjuvant or adjuvant therapy.	Drug: DKN-01 300mg; Administered by IV infusion; Drug: DKN-01 400mg; Administered by IV infusion
Experimental: Part B2 Second Line Treatment; 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; Administered by IV infusion; Drug: DKN-01 400mg; Administered by IV infusion
Active Comparator: Part C Control First Line Treatment; 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; Administered by IV infusion; Drug: Tislelizumab 400mg; Administered by IV infusion; Drug: Oxaliplatin; Administered by IV infusion; Drug: Capecitabine 1000mg/ m2 BID; Administered orally; Other Name: Xeloda; Drug: Leucovorin Calcium; Administered by IV infusion; Other Name: Folinic acid; Drug: Fluorouracil; Administered by IV infusion
Experimental: Part C Experimental First Line Treatment; 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; Administered by IV infusion; Drug: DKN-01 400mg; Administered by IV infusion; Drug: Tislelizumab 200mg; Administered by IV infusion; Drug: Tislelizumab 400mg; Administered by IV infusion; Drug: Oxaliplatin; Administered by IV infusion; Drug: Capecitabine 1000mg/ m2 BID; Administered orally; Other Name: Xeloda; Drug: Leucovorin Calcium; Administered by IV infusion; Other Name: Folinic acid; Drug: Fluorouracil; Administered by IV infusion

Outcome Measures

Primary Outcome Measures :

1. Part A and B: Safety and Tolerability of DKN-01 in G/GEJ patients [ Time Frame: approximately 6 months ]
   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.
2. Part C: Progression Free Survival (PFS) in G/GEJ DKK1 high patients treated with DKN-01 in combination with tislelizumab and chemotherapy vs tislelizumab and chemotherapy as a first-line therapy [ Time Frame: approximately 12 months ]
   To assess whether the addition of DKN-01 to the combination of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6 [leucovorin calcium, fluorouracil, and oxaliplatin]) improves PFS according to the RECIST v1.1 as assessed by the Investigator in patients with advanced DKK1-high G/GEJ adenocarcinoma compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy

Secondary Outcome Measures :

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 [ Time Frame: approximately 6 months ]
   Objective Response Rate (ORR) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
2. Part B: Objective Response Rate (ORR) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
   Objective Response Rate (ORR) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
3. Part A:Duration of response (DoR) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Duration of Response (DoR) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy
4. Part A:Duration of complete response (DoCR) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Duration of complete response (DoCR) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy
5. Part A:Progression free survival (PFS) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Progression free survival (PFS) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy
6. Part A:Overall survival (OS) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Overall survival (OS) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy.
7. Part A:Duration of clinical benefit (DoCB) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Duration of clinical benefit (DoCB) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy.
8. Part A:Durable clinical benefit (DCB) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Durable clinical benefit (DCB) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy.
9. Part A:Disease control rate (DCR) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy [ Time Frame: approximately 6 months ]
   Disease control rate (DCR) in inoperable, locally advanced or metastatic G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy.
10. Part B:Duration of Response (DoR) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
    Duration of Response (DoR) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy
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 [ Time Frame: approximately 6 months ]
    Duration of complete response (DoCR) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
12. Part B:Progression free survival (PFS) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
    Progression free survival (PFS) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
13. Part B:Overall survival (OS) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
    Overall survival (OS) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
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 [ Time Frame: approximately 6 months ]
    Duration of clinical benefit (DoCB) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
15. Part B:Durable clinical benefit (DCB) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
    Durable clinical benefit (DCB) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
16. Part B:Disease control rate (DCR) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: approximately 6 months ]
    Disease control rate (DCR) in inoperable, locally advanced or metastatic DKK1-high G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy.
17. Part C:To determine whether the addition of DKN-01 to the combination of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) improves PFS as a first-line therapy. [ Time Frame: approximately 12 months ]
    To determine whether the addition of DKN-01 to the combination of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) improves PFS, according to RECIST v1.1, as assessed by the Investigator, in all patients with advanced G/GEJ adenocarcinoma compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy.
18. 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. [ Time Frame: approximately 12 months ]
    To estimate the objective response rate (ORR), according to RECIST v1.1, as assessed by the Investigator, the duration of response (DoR) and overall survival (OS) in advanced DKK1-high and overall G/GEJ adenocarcinoma patients treated with DKN-01 in combination with tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy.
19. 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. [ Time Frame: approximately 12 months ]
    To estimate the objective response rate (ORR), according to RECIST v1.1, as assessed by the Investigator, the duration of response (DoR) and overall survival (OS) in advanced DKK1-high and overall G/GEJ adenocarcinoma patients treated with DKN-01 in combination with tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy.
20. 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. [ Time Frame: approximately 12 months ]
    To estimate the objective response rate (ORR), according to RECIST v1.1, as assessed by the Investigator, the duration of response (DoR) and overall survival (OS) in advanced DKK1-high and overall G/GEJ adenocarcinoma patients treated with DKN-01 in combination with tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy.
21. Part C:To assess whether the addition of DKN-01 with tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) improves PFS and ORR in patients with CPS ≥5 or CPS <5 advanced DKK1-high and overall G/GEJ adenocarcinoma as a first-line therapy. [ Time Frame: approximately 12 months ]
    To assess whether the addition of DKN-01 to the combination of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) improves PFS and ORR, according to RECIST v1.1, as assessed by the Investigator, in patients with CPS ≥5 or CPS <5 advanced DKK1-high and overall G/GEJ adenocarcinoma compared to tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) as a first-line therapy.
22. Part C:To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each of the treatment arms. [ Time Frame: approximately 12 months ]
    To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each of the treatment arms.

Other Outcome Measures:

1. The maximum plasma concentration (C max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
   The maximum plasma concentration (C max) will be measured.
2. The time taken to reach the maximum plasma concentration (T max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
   The time taken to reach the maximum plasma concentration (T max) will be measured.
3. Area Under the Curved (AUC) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Area Under the Curved (AUC) will be measured.
4. Concentration of anti-DKN-01 antibodies in human serum in G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy. [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Concentration of anti-DKN-01 antibodies in human serum in patients with inoperable, locally advanced or metastatic G/GEJ treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy.
5. Concentration of anti-DKN-01 antibodies in human serum in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Concentration of anti-DKN-01 antibodies in human serum in patients with inoperable, locally advanced or metastatic DKK1-high G/GEJ treated with DKN-01 in combination with tislelizumab as a second-line therapy
6. Concentration of anti-tislelizumab antibodies in human serum in G/GEJ patients treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Concentration of anti-tislelizumab antibodies in human serum in patients with inoperable, locally advanced or metastatic G/GEJ treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy
7. Concentration of anti-tislelizumab antibodies in human serum in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Concentration of anti-tislelizumab antibodies in human serum in patients with inoperable, locally advanced or metastatic DKK1-high G/GEJ treated with DKN-01 in combination with tislelizumab as a second-line therapy
8. Dickkopf-1 (DKK1) concentration in serum and plasma relative to safety and efficacy outcomes in G/GEJ patients [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Dickkopf-1 (DKK1) concentration in serum and plasma relative to safety and efficacy outcomes in patients with inoperable, locally advanced or metastatic G/GEJ treated with DKN-01 in combination with tislelizumab + CAPOX as a first-line therapy
9. Dickkopf-1 (DKK1) concentration in serum and plasma relative to safety and efficacy outcomes in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy [ Time Frame: Baseline to study completion (approximately 6 months) ]
   Dickkopf-1 (DKK1) concentration in serum and plasma relative to safety and efficacy outcomes in patients with inoperable, locally advanced or metastatic DKK1-high G/GEJ treated with DKN-01 in combination with tislelizumab as a second-line therapy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion:

Part A & C:

1. 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:

2. Disease progression during first-line therapy or within 4 months after the last dose of first-line therapy.

3. Documentation of elevated DKK1 mRNA expression from a fresh tumor biopsy or a biopsy obtained within the 6 months of screening.

   Part C Only:

4. Documentation of PD-L1 CPS by 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:

5. Able to provide written informed consent prior to any study-specific procedures.
6. Age ≥18 years on the day of signing the informed consent (exception: ≥19 years in the Republic of Korea).
7. Confirmed diagnosis of gastric adenocarcinoma or GEJ adenocarcinoma.
8. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.
9. Tumor tissue for mandatory pre-treatment evaluation (fresh biopsy [preferred] or archived specimen).
10. ECOG performance status ≤ 1 within 7 days of first dose of study drug
11. Acceptable liver, renal, hematologic, and coagulation function
12. 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.
13. 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.

Exclusion:

Part A & C Only:

1. Diagnosis of HER2-positive G/GEJ adenocarcinoma.
2. 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).

3. Prior therapy with an anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody.

   Part B Only:

4. Major surgery or chemotherapy within 21 days of first dose of study drug.

   General:

5. Squamous cell or undifferentiated or other histological type of gastric cancer.
6. 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.
7. Patients with active autoimmune diseases or history of autoimmune diseases that may relapse.
8. Any condition that required treatment with steroids or any other immune suppressive drugs within 14 days prior to first dose of study drug.
9. Active leptomeningeal disease or uncontrolled brain metastases.
10. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
11. 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.
12. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to first dose of study drug.
13. Clinically significant anorexia within 7 days prior to first dose of study drug.
14. History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases.
15. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
16. Prior allogeneic stem cell transplantation or organ transplantation.
17. History of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment.
18. Known dihydropyrimidine dehydrogenase deficiency.
19. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
20. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
21. Known to be human immunodeficiency virus (HIV) positive.
22. Serious nonmalignant disease
23. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
24. Known osteoblastic bony metastasis.
25. History of gastrointestinal perforation and/or fistulae within 6 months prior to first dose of study drug.
26. Major surgery 28 days prior to study entry.
27. Serious psychiatric or medical conditions that could interfere with treatment.
28. Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities).
29. Administration of a live vaccine within 28 days before first dose of study drug.
30. Active substance abuse.
31. Pregnant or nursing.
32. Concurrent participation in another therapeutic clinical study.
33. Prior radiation therapy within 14 days prior to study entry.

Contacts and Locations

Contacts

Contact: Cynthia Sirard, MD; 617-714-0357; CSirard@leaptx.com

Contact: Elizabeth Parker; Eparker@leaptx.com

Locations

United States, Arizona

Mayo Clinic Cancer Center; Recruiting

Phoenix, Arizona, United States, 85054

Contact: Clinical Trials Referral Office 507-283-2511 CancerResearch@mayo.edu

University of Arizona; Recruiting

Tucson, Arizona, United States, 85724

Contact: Daniel Pennington 520-694-9065 danielpennington@arizona.edu

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

Contact: Tina Zhang 626-218-0867 tizhang@coh.org

The Angeles Clinic Research Institute - A Cedars-Sinai Affiliate; Recruiting

Los Angeles, California, United States, 90025

Contact: Saba Mukarram 310-231-2181 smukarram@theangelesclinic.org

University of Southern California; Recruiting

Los Angeles, California, United States, 90033

Contact: Charlean Ketchens 323-865-3035 ketchens_c@med.usc.edu

UCLA; Recruiting

Los Angeles, California, United States, 90095

Contact: Lisa Yonemoto 310-633-8400 lyonemoto@mednet.ucla.edu

Hoag Memorial Hospital Presbyterian; Recruiting

Newport Beach, California, United States, 92663

Contact: Leila Andres 949-764-8092 Leila.andres@hoag.org

Chao Family Comprehensive Cancer Center, University of California, Irvine; Recruiting

Orange, California, United States, 92868

Contact: Farshid Dayyani, MD, PhD 877-827-8839 ucstudy@uci.edu

University of California San Francisco; Recruiting

San Francisco, California, United States, 94158

Contact: Andrew Ko, MD 877-827-3222 cancertrials@ucsf.edu

United States, Florida

Mayo Clinic Florida; Recruiting

Jacksonville, Florida, United States, 32224

Contact: Kaitlin S Marrache 904-953-4404 marrache.kaitlin@mayo.edu

AdventHealth Cancer Institute; Recruiting

Orlando, Florida, United States, 32804

Contact: Elizabeth Griffith 407-303-2800 ext 1101783 Elizabeth.Griffith@AdventHealth.com

H. Lee Moffitt Cancer Center and Research Institute; Not yet recruiting

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern University Robert H. Lurie Comprehensive Cancer Center; Recruiting

Chicago, Illinois, United States, 60611

Contact: Study Coordinator 312-695-1301 cancertrials@northwestern.edu

University of Chicago; Recruiting

Chicago, Illinois, United States, 60637

United States, Louisiana

Pontchartrain Cancer Center; Active, not recruiting

Covington, Louisiana, United States, 70433

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Patricia Lynch, RN 617-724-4000 lynch.patricia2@mgh.harvard.edu

Beth Israel Deaconess Medical Center; Active, not recruiting

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute; Active, not recruiting

Boston, Massachusetts, United States, 02215

United States, New York

Columbia University Irving Medical Center; Recruiting

New York, New York, United States, 10032

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Terrance Lawrence 919-668-1861 Terrance.Lawrence@duke.edu

United States, Pennsylvania

Fox Chase Cancer Center; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19111

United States, Rhode Island

Rhode Island Hospital; Recruiting

Providence, Rhode Island, United States, 02903

Contact: Andrew Schumacher 401-444-3234 aschumacher@lifespan.org

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Jackie Smith, RN 713-792-2828 JSmith19@mdanderson.org

United States, Wisconsin

University of Wisconsin Carbone Cancer Center; Active, not recruiting

Madison, Wisconsin, United States, 53792

Germany

Charité Universitätsmedizin Berlin; Not yet recruiting

Berlin, Germany, 13353

Institut Fur Klinisch Onkologische Forschung Am Krankenhaus Nordwest; Not yet recruiting

Frankfurt, Germany, 60488

Hämatologisch-Onkologische Praxis Eppendorf (HOPE); Not yet recruiting

Hamburg, Germany, 20249

Universitatsklinikum Heidelberg; Not yet recruiting

Heidelberg, Germany, 69120

Slk-Kliniken; Not yet recruiting

Heilbronn, Germany, 74078

Universitätsklinikum Mainz Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz; Not yet recruiting

Mainz, Germany, 55131

Studienzentrum Onkologie Ravensburg; Not yet recruiting

Ravensburg, Germany, 88212

Caritas Klinikum Saarbrücken St. Theresia; Not yet recruiting

Saarbrücken, Germany, 66113

Korea, Republic of

CHA Bundang Medical Center; Recruiting

Seongnam, Gyeonggi-do, Korea, Republic of, 13520

Contact: Hong Jae Chon, MD 82-31-780-5000

Korea University Ansan Hospital; Recruiting

Ansan-si, Korea, Republic of, 15355

Hallym University Sacred Heart Hospital; Active, not recruiting

Anyang, Korea, Republic of, 14068

Dong-A University Hospital; Recruiting

Busan, Korea, Republic of, 49201

Contact: Sung Yong Oh, MD 82-51-240-2306

National Cancer Center; Recruiting

Goyang, Korea, Republic of, 10408

Contact: Young-lee Park, MD 82-31-920-0114

Gachon University Gil Medical Center; Recruiting

Incheon, Korea, Republic of, 21565

Contact: Sun Jin Sym, MD 82-32-460-3213

Inha University Hospital; Recruiting

Incheon, Korea, Republic of, 22332

Contact: Mooh-Hee Lee, MD 82-32-890-2080

Seoul National University Bundang Hospital; Recruiting

Seongnam, Korea, Republic of, 13620

Contact: Keun-Wook Lee, MD 82-31-787-2034

Korea University Anam Hospital; Not yet recruiting

Seoul, Korea, Republic of, 02841

Hanyang University Hospital; Recruiting

Seoul, Korea, Republic of, 04763

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 05505

Boramae Hospital SNU; Recruiting

Seoul, Korea, Republic of, 07061

Korea University Guro Hospital; Not yet recruiting

Seoul, Korea, Republic of, 08308

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 3080

Contact: Do-Youn Oh, MD 82-2-2072-0505

Severance Hospital, Yonsei University Health System; Recruiting

Seoul, Korea, Republic of, 3722

Contact: Hyun Cheol Chung, MD 82-2-2228-5800

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 6351

Contact: Jeeyun Lee, MD 82-2-3410-0200

The Catholic University of Korea St. Mary's Hospital; Recruiting

Seoul, Korea, Republic of, 6591

Contact: In-Ho Kim, MD 82-2-2258-5745

The Catholic University of Korea St. Vincent's Hospital; Recruiting

Suwon, Korea, Republic of, 16247

Contact: Byoung Yong Shim, MD 82-31-249-8016

United Kingdom

University of Dundee - Ninewells Hospital And Medical School; Not yet recruiting

Dundee, United Kingdom, DD1 9SY

Royal Surrey County Hospital NHS Foundation Trust; Not yet recruiting

Guildford, United Kingdom, GU2 7XX

Leicester Cancer Research Centre; Not yet recruiting

Leicester, United Kingdom, LE1 7RH

University College Longon Hospitals - NHS Trust; Not yet recruiting

London, United Kingdom, NW1 2PG

Guy's and St Thomas' NHS Foundation Trust; Not yet recruiting

London, United Kingdom, SE1 7EH

The Christie NHS Foundation Trust - The Christie Clinic; Not yet recruiting

Manchester, United Kingdom, M20 4BX

The Royal Marsden NHS Foundation Trust - Institute of Cancer Research (ICR) - Sutton; Not yet recruiting

Sutton, United Kingdom, SM2 5PT

Musgrove Park - Somerset NHS Foundation Trust; Not yet recruiting

Taunton, United Kingdom, TA1 5DA

Sponsors and Collaborators

Leap Therapeutics, Inc.

BeiGene

Investigators

• Study Director: Cynthia Sirard, MD; Chief Medical Officer

More Information

• Responsible Party: Leap Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04363801
• Other Study ID Numbers: DEK-DKK1-P205
• First Posted: April 27, 2020
• Last Update Posted: June 5, 2023
• Last Verified: June 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Leap Therapeutics, Inc.:

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

Additional relevant MeSH terms:

Adenocarcinoma; Stomach Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Leucovorin; Fluorouracil; Capecitabine; Oxaliplatin; Tislelizumab; Calcium; Levoleucovorin; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antidotes; Protective Agents; Vitamin B Complex