Purpose

A Phase 2a, 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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


1. Part A:

• 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.

2. Part B:

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

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

3. Able to provide written informed consent prior to any study-specific procedures.

4. Confirmed diagnosis of gastric adenocarcinoma or GEJ adenocarcinoma.

5. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.

6. ECOG performance status ≤ 1 within 7 days of first dose of study drug

7. Acceptable liver, renal, hematologic, and coagulation function

8. 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.

Exclusion:

1. Part A:

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

2. Unable to swallow capsules or disease significantly affected gastrointestinal
function (add diseases as examples).

2. Part B:

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

3. Patients with active autoimmune diseases or history of autoimmune diseases that may
relapse.

4. Any condition that required treatment with steroids or any other immune suppressive
drugs within 14 days prior to first dose of study drug.

5. Active leptomeningeal disease or uncontrolled brain metastases.

6. Any active cancer ≤ 2 years before first dose of study drug with the exception of
cancer for this study.

7. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, or unstable arrhythmia.

8. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital
long QT syndrome.

9. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study
entry requiring systemic therapy.

10. Serious nonmalignant disease

11. Pregnant or nursing.

12. 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.

13. Known osteoblastic bony metastasis.

14. Major surgery 28 days prior to study entry.

15. Prior radiation therapy within 14 days prior to study entry.

16. Previously treated with an anti-DKK1 therapy, PD-1, anti-PD-L1, anti-PD-L-2

17. Significant allergy to a pharmaceutical therapy that, in the opinion of the
Investigator, poses an increased risk to the patient.

18. Active substance abuse.

19. Known dihydropyrimidine dehydrogenase deficiency.

20. Administration of a live vaccine within 28 days before first dose of study drug.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: Tislelizumab 200mg
    Administered by IV infusion
  • Drug: Oxaliplatin 130mg/m2
    Administered by IV infusion
  • Drug: Capecitabine 1000mg/ m2 BID
    Administered orally
    Other names:
    • Xeloda
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: Tislelizumab 200mg
    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: Tislelizumab 200mg
    Administered by IV infusion

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Patricia Lynch, RN
617-724-4000
lynch.patricia2@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Leap Therapeutics, Inc.

Study Contact

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

Detailed Description

This is a Phase 2a nonrandomized, open-label, multicenter study to be conducted concurrently in 2 Parts (Parts A and B). Approximately 72 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. Both parts 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. Parts A and B will be enrolled concurrently. Two doses of DKN-01 will be evaluated in Part B (Part B1 and Part B2)

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.