Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

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

Official Title

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 (DisTinGuish)

Details

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)

Keywords

Gastric Cancer Gastric Adenocarcinoma GastroEsophageal Cancer Gastroesophageal junction cancer adenocarcinoma DKK1 Tislelizumab DKN-01 Stomach Neoplasms Capecitabine Oxaliplatin DKN-01 300mg DKN-01 600mg Tislelizumab 200mg Oxaliplatin 130mg/m2 Capecitabine 1000mg/ m2 BID

Eligibility

For people ages 18 years and up

  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.

  1. Part B:
  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.
  4. Able to provide written informed consent prior to any study-specific procedures.
  5. Confirmed diagnosis of gastric adenocarcinoma or GEJ adenocarcinoma.
  6. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.
  7. ECOG performance status ≤ 1 within 7 days of first dose of study drug
  8. Acceptable liver, renal, hematologic, and coagulation function
  9. 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:
  2. Diagnosis of HER2-positive G/GEJ adenocarcinoma.
  3. Unable to swallow capsules or disease significantly affected gastrointestinal function (add diseases as examples).
  4. Part B:
  5. Major surgery or chemotherapy within 21 days of first dose of study drug.
  6. Patients with active autoimmune diseases or history of autoimmune diseases that may relapse.
  7. Any condition that required treatment with steroids or any other immune suppressive drugs within 14 days prior to first dose of study drug.
  8. Active leptomeningeal disease or uncontrolled brain metastases.
  9. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study.
  10. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  11. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
  12. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy.
  13. . Serious nonmalignant disease
  14. . Pregnant or nursing.
  15. . 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.
  16. . Known osteoblastic bony metastasis.
  17. . Major surgery 28 days prior to study entry.
  18. . Prior radiation therapy within 14 days prior to study entry.
  19. . Previously treated with an anti-DKK1 therapy, PD-1, anti-PD-L1, anti-PD-L-2
  20. . Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient.
  21. . Active substance abuse.
  22. . Known dihydropyrimidine dehydrogenase deficiency.
  23. . Administration of a live vaccine within 28 days before first dose of study drug.

Locations

  • University of California San Francisco not yet accepting patients
    San Francisco California 94158 United States
  • The Angeles Clinic Research Institute not yet accepting patients
    Los Angeles California 90025 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Leap Therapeutics, Inc.
ID
NCT04363801
Phase
Phase 2
Study Type
Interventional
Last Updated