DKN-01 + Tislelizumab for Stomach Cancer
(DisTinGuish Trial)

Recruiting in Palo Alto (17 mi)

+57 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Leap Therapeutics, Inc.

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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

Eligibility Criteria

Adults with inoperable, advanced gastric or gastroesophageal cancer who haven't had previous cancer therapy (or have been treatment-free for 6+ months) can join. They must show elevated DKK1 mRNA from a biopsy and agree to contraception use. Exclusions include HER2-positive diagnosis, recent major surgery or chemo, active infections, certain heart conditions, uncontrolled diseases like diabetes, prior treatments with specific antibodies including anti-PD-1/L1/L2 or anti-DKK1 agents.

Inclusion Criteria

I agree to use effective birth control during and for 6 months after the study.

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

I am at least 18 years old, or 19 if I'm from the Republic of Korea.

+9 more

Exclusion Criteria

I have not experienced significant loss of appetite in the week before starting the study drug.

I do not have any ongoing serious infections needing treatment.

I have a serious illness that is not cancer.

+28 more

Participant Groups

The trial is testing the effectiveness of DKN-01 in combination with Tislelizumab and possibly chemotherapy as first-line or second-line therapy. Patients will receive varying doses of these drugs to see how well they work together against stomach cancers that express a particular gene marker (DKK1).

5Treatment groups

Experimental Treatment

Active Control

Group I: Part C Experimental First Line TreatmentExperimental Treatment8 Interventions

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.

Group II: Part B2 Second Line TreatmentExperimental Treatment3 Interventions

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.

Group III: Part B1 Second Line TreatmentExperimental Treatment3 Interventions

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.

Group IV: Part A First Line TreatmentExperimental Treatment5 Interventions

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.

Group V: Part C Control First Line TreatmentActive Control8 Interventions

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.

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Xeloda for: