Clinical Trials /

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

NCT04363801

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy in Patients With Gastric or Gastroesophageal Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: DEK-DKK1-P205
  • NCT ID: NCT04363801

Conditions

  • Gastric Cancer
  • Gastric Adenocarcinoma
  • GastroEsophageal Cancer

Interventions

DrugSynonymsArms
DKN-01 300mgPart A First Line Treatment
DKN-01 600mgPart B2 Second Line Treatment
Tislelizumab 200mgPart A First Line Treatment
Oxaliplatin 130mg/m2Part A First Line Treatment
Capecitabine 1000mg/ m2 BIDXelodaPart A First Line Treatment

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

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)
    

Trial Arms

NameTypeDescriptionInterventions
Part A First Line TreatmentExperimentalPart 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.
  • DKN-01 300mg
  • Tislelizumab 200mg
  • Oxaliplatin 130mg/m2
  • Capecitabine 1000mg/ m2 BID
Part B1 Second Line TreatmentExperimentalPart 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.
  • DKN-01 300mg
  • Tislelizumab 200mg
Part B2 Second Line TreatmentExperimentalPart 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.
  • DKN-01 600mg
  • Tislelizumab 200mg

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability of DKN-01 in G/GEJ patients
Time Frame:approximately 6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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).
Measure: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
Safety Issue:
Description: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).
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure:Overall survival (OS) in G/GEJ patients treated with DKN-01 with tislelizumab + CAPOX as a first-line therapy
Time Frame:approximately 6 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure:Progression free surviva (PFS) in G/GEJ patients treated with DKN-01 in combination with tislelizumab as a second-line therapy
Time Frame:approximately 6 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Leap Therapeutics, Inc.

Trial Keywords

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

Last Updated

April 23, 2020