A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination with Tislelizumab ± Chemotherapy as First Line orSecond-Line Therapy in Adult Patients with Inoperable, Locally Advanced or Metastatic Gastric or GastroesophagealJunction Adenocarcinoma (DisTinGuish)
- Conditions
- Gastric Adenocarcinoma, Gastric cancer, GastroEsophageal CancerTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-504940-32-00
- Lead Sponsor
- eap Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 232
Part A and C only: No previous systemic therapy for inoperable, locally advanced or metastatic G/GEJ adenocarcinoma. a. Patients may have received prior neoadjuvant or adjuvant therapy as long as it was completed without disease recurrence for at least 6 months since last treatment., General: Acceptable renal function: a. Serum creatinine =1.5 × ULN or estimated glomerular filtration rate =30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation, General: Acceptable hematologic status (in the Republic of Korea patients must not have required blood transfusion or growth factor support within 14 days before sample collection at Screening for the following): a. Absolute neutrophil count (ANC) =1.5 × 109/L. b. Platelets: i. Part A and C only: =100 × 109/L ii. Part B only: =75 × 109/L c. Hemoglobin =9 g/dL, General: ECOG performance status =1 within 7 days of first dose of study drug., General: Acceptable liver function: a. Parts A and B only: i. Total bilirubin =2.0 times upper limit of normal (ULN). Total bilirubin must be <3 × ULN for patients with Gilbert’s syndrome. ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 times ULN (if liver metastases are present, then =5 × ULN is allowed). b. Part C only: i. Total bilirubin =2.0 times upper limit of normal (ULN). ii. AST and ALT =2.5 times ULN. 1. If liver metastases are present, then =5 × ULN is allowed (excluding Republic of Korea)., Part B only: Documented objective radiographic or symptomatic disease progression following first-line therapy with any platinum and/or fluoropyrimidine-based regimen for unresectable or metastatic disease. a. Patients may have received prior neoadjuvant or adjuvant therapy. If progression has occurred within 6 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as 1 line of therapy for advanced disease. b. Prior trastuzumab (or biosimilar) treatment is acceptable for patients with history of HER2-positive G/GEJ adenocarcinoma. c. Prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1 in any treatment setting (including adjuvant/neoadjuvant) is acceptable., Part B only: Documentation of elevated DKK1 mRNA expression in tumor cells from a fresh tumor biopsy (preferred) or archived tumor biopsy specimen. High DKK1 is defined as an H-score =35 in mRNA by ISH conducted in a Sponsor designated central laboratory, General: 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 a. A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility. b. Males with known low sperm counts” (consistent with sub-fertility”) are not to be considered sterile for purposes of this study., Part C only: 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: Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments., General: Age =18 years on the day of signing the informed consent (exception: =19 years in the Republic of Korea), General: Histologically proven gastric adenocarcinoma or Siewert I-III GEJ adenocarcinoma,
Part A and C only: Diagnosis of HER2-positive G/GEJ adenocarcinoma., General: Clinically significant anorexia (CTCAE =Grade 2) within 7 days prior to first dose of study drug., General: Any active malignancy =2 years before first dose of study drug, with the exception of the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)., General: Known dihydropyrimidine dehydrogenase deficiency, Part A and C only: Unable to swallow capsules or disease significantly affecting 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)., Part A and C only: Prior therapy with an anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody, Part B only: Systemic anti-cancer therapy (e.g., chemotherapy or immunotherapy) within 21 days prior to first dose of study drug., General: Prior allogeneic stem cell transplantation or organ transplantation, General: Known osteoblastic bony metastasis. Screening of patients without a history of metastatic bony lesions is not required, General: History of gastrointestinal perforation and/or fistulae within 6 months prior to first dose of study drug, clinically significant bleeding from the gastrointestinal tract within 1 month prior to first dose of study drug, or clinically significant bowel obstruction (CTCAE =Grade 2)., General: Major surgery within 4 weeks of first dose of study drug, General: Prior allogeneic stem cell transplantation or organ transplantation, General: Serious psychiatric or medical conditions that could interfere with treatment., General: Any of the following cardiovascular risk factors: a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, within 28 days before first dose of study drug b. Pulmonary embolism within 28 days before first dose of study drug c. Any history of acute myocardial infarction within 6 months before first dose of study drug d. Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV within 6 months before first dose of study drug e. Any event of ventricular arrhythmia =Grade 2 in severity within 6 months before first dose of study drug f. Any history of cerebrovascular accident within 6 months before first dose of study drug g. Uncontrolled hypertension that cannot be managed by standard anti-hypertension medications within 28 days before first dose of study drug h. Any episode of syncope or seizure within 28 days before first dose of study drug., General: Squamous cell or undifferentiated or other histological type of gastric cancer., General: 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 (Part B exception, see entry criterion 2c), General: Active autoimmune diseases or history of autoimmune diseases that may relapse. a. Note: Patients with the following diseases are not excluded and may proceed to further Screening: i. Controlled Type I diabetes ii. Hypothyroidism (provided it is managed with hormone replacement th
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method