Gastric Adenocarcinoma, Gastric Cancer, GastroEsophageal Cancer
Conditions
Keywords
Gastric cancer, Gastroesophageal junction, cancer, adenocarcinoma, DKK1, Tislelizumab, DKN-01
Brief summary
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
Detailed description
This is a Phase 2 open-label, multicenter study to be conducted concurrently in 3 Parts (Parts A, B, and C). Approximately 232 patients aged 18 years or older with inoperable, histologically confirmed locally advanced or metastatic Gastric or Gastroesophageal Junction (G/GEJ) adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy will be enrolled in the study. Part A and B 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. Two doses of DKN-01 will be evaluated in Part B (Part B1 and Part B2). Part C is the open-label, randomized, controlled, 2-arm portion of the study to evaluate the efficacy and safety of tislelizumab + chemotherapy regimen (CAPOX or mFOLFOX6) ± DKN-01 in adult patients with inoperable, histologically confirmed locally advanced or metastatic G/GEJ adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy. Approximately 160 patients will be randomized in a 1:1 ratio to receive either DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6) (n=80) or tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) (n=80).
Interventions
DRUGDKN-01 300mg
Administered by IV infusion
DRUGDKN-01 600mg
Administered by IV infusion
DRUGDKN-01 400mg
Administered by IV infusion
DRUGTislelizumab 200mg
Administered by IV infusion
DRUGTislelizumab 400mg
Administered by IV infusion
DRUGOxaliplatin
Administered by IV infusion
DRUGCapecitabine 1000mg/ m2 twice daily (BID)
Administered orally
DRUGLeucovorin Calcium
Administered by IV infusion
DRUGFluorouracil
Administered by IV infusion
Sponsors
BeiGene
Leap Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: Part A & C: 1. 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. Part B Only: 2. Disease progression during first-line therapy or within 4 months after the last dose of first-line therapy. 3. Documentation of elevated Dickkopf-1 (DKK1) messenger ribonucleic acid (mRNA) expression from a fresh tumor biopsy or a biopsy obtained within the 6 months of screening. Part C Only: 4. Documentation of programmed cell death protein ligand-1 (PD-L1) combined positive score (CPS) by immunohistochemistry (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: 5. Able to provide written informed consent prior to any study-specific procedures. 6. Age ≥18 years on the day of signing the informed consent (exception: ≥19 years in the Republic of Korea). 7. Confirmed diagnosis of gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma. 8. One or more tumors measurable on radiographic imaging as defined by Response Evaluation Criteria in Solid Tumor (RECIST) 1.1. 9. Tumor tissue for mandatory pre-treatment evaluation (fresh biopsy \[preferred\] or archived specimen). 10. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 within 7 days of first dose of study drug 11. Acceptable liver, renal, hematologic, and coagulation function 12. 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. 13. 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. Exclusion: Part A & C Only: 1. Diagnosis of HER2-positive G/GEJ adenocarcinoma. 2. Unable to swallow capsules or disease significantly affected 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). 3. Prior therapy with an anti-programmed cell death protein 1 (PD-1) or anti-PD-L1 antibody. Part B Only: 4. Major surgery or chemotherapy within 21 days of first dose of study drug. General: 5. Squamous cell or undifferentiated or other histological type of gastric cancer. 6. 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. 7. Patients with active autoimmune diseases or history of autoimmune diseases that may relapse. 8. Any condition that required treatment with steroids or any other immune suppressive drugs within 14 days prior to first dose of study drug. 9. Active leptomeningeal disease or uncontrolled brain metastases. 10. Any active cancer ≤ 2 years before first dose of study drug with the exception of cancer for this study. 11. Uncontrolled diabetes or \>Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥Grade 3 hypoalbuminemia within 14 days before first dose of study drug. 12. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage within 7 days prior to first dose of study drug. 13. Clinically significant anorexia within 7 days prior to first dose of study drug. 14. History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or uncontrolled systemic diseases. 15. Active, uncontrolled bacterial, viral, or fungal infections, within 14 days of study entry requiring systemic therapy. 16. Prior allogeneic stem cell transplantation or organ transplantation. 17. History of severe hypersensitivity reactions to other monoclonal antibodies or any components of study treatment. 18. Known dihydropyrimidine dehydrogenase deficiency. 19. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia. 20. Fridericia-corrected QT interval (QTcF) \> 470 msec (female) or history of congenital long QT syndrome. 21. Known to be human immunodeficiency virus (HIV) positive. 22. Serious nonmalignant disease 23. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and clinically significant. 24. Known osteoblastic bony metastasis. 25. History of gastrointestinal perforation and/or fistulae within 6 months prior to first dose of study drug. 26. Major surgery 28 days prior to study entry. 27. Serious psychiatric or medical conditions that could interfere with treatment. 28. Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for Adverse Events (AEs) not considered a likely safety risk (e.g., alopecia, neuropathy, and specific laboratory abnormalities). 29. Administration of a live vaccine within 28 days before first dose of study drug. 30. Active substance abuse. 31. Pregnant or nursing. 32. Concurrent participation in another therapeutic clinical study. 33. Prior radiation therapy within 14 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | approximately 28 months | 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. |
| Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy | approximately 30 months | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. |
| Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | DoCR is defined as the time from initial complete response (CR) until radiographically documented progressive disease or death due to any cause, whichever is first. |
| Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. |
| Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. |
| Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | DoCB is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. |
| Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | Durable clinical benefit (DCB) is defined as the proportion of patients presenting a Duration of clinical benefit (DoCB) for ≥180 days from initiation of DKN-01. Patients who have a best overall response of PD or those with clinical benefit lasting \<180 days are not included. |
| Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. |
| Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier. |
| Part B: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | Duration of complete response (DoCR) is defined as the time from initial CR until radiographically documented progressive disease or death due to any cause, whichever is first. No patients had a complete response (CR); therefore, the DoCR was not applicable. |
| Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. |
| Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy | approximately 28 months | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) through radiological assessment of tumor response, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Investigators were urged to have the same radiographic imaging modality used throughout the study for each subject (at baseline and at subsequent assessments) in order to provide uniformity of radiographic assessments. |
| Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | Duration of clinical benefit (DoCB) is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks. |
| Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | DCB rate is defined as the proportion of patients presenting a DoCB (Duration of clinical benefit) for ≥ 180 days from initiation of DKN-01, Patients who have a best overall response of PD or those with clinical benefit lasting \<180 days will not be included. |
| Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1. |
| Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | approximately 30 months | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX |
| Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | approximately 30 months | The duration of response (DoR) is defined only for responders (patients with a BOR of CR or PR) at the time from initial response (CR or PR) until radiographically documented progressive disease or death due to any cause, whichever is earlier. For ORR patient without PD or death, DoR is censored at the most recent tumor assessment before the data cutoff or study withdrawal, whichever occurs first. |
| Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | approximately 30 months | Overall survival (OS) OS is defined as the time from the date of randomization to death due to any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored at the date the patient was last known to be alive (i.e., date of last contact). Patients lacking data beyond the day of randomization is censored at the date of randomization (i.e., OS duration of 1 day). |
| Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | approximately 30 months | PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first. |
| Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | approximately 30 months | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Risk difference (RD)(%) or ORR: Positive RD implies the exposure is associated with a higher probability of the outcome occurring. Negative RD indicates the exposure is associated with a lower probability of the outcome occurring. |
| Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms. | approximately 30 months | To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each treatment arm: Control (tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) and Experimental (DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6)) |
| Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause. |
| Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | approximately 28 months | Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). |
Countries
Germany, South Korea, United States
Participant flow
Recruitment details
This was a Phase 2 open-label, multicenter study conducted concurrently in 3 parts: Non-randomized Parts A and B, and a randomized Part C.
Participants by arm
| Arm | Count |
|---|---|
| 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.
DKN-01 300mg: Administered by IV infusion
DKN-01 400mg: Administered by IV infusion
Tislelizumab 200mg: Administered by IV infusion
Tislelizumab 400mg: Administered by IV infusion | 25 |
| 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.
DKN-01 300mg: Administered by IV infusion
DKN-01 400mg: Administered by IV infusion | 24 |
| 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.
DKN-01 600mg: Administered by IV infusion
DKN-01 400mg: Administered by IV infusion | 28 |
| Part C Control First Line Treatment 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.
Tislelizumab 200mg: Administered by IV infusion
Tislelizumab 400mg: Administered by IV infusion
Oxaliplatin: Administered by IV infusion
Capecitabine 1000mg/ m2 BID: Administered orally
Leucovorin Calcium: Administered by IV infusion
Fluorouracil: Administered by IV infusion | 85 |
| Part C Experimental First Line Treatment 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.
DKN-01 600mg: Administered by IV infusion
DKN-01 400mg: Administered by IV infusion
Tislelizumab 200mg: Administered by IV infusion
Tislelizumab 400mg: Administered by IV infusion
Oxaliplatin: Administered by IV infusion
Capecitabine 1000mg/ m2 BID: Administered orally
Leucovorin Calcium: Administered by IV infusion
Fluorouracil: Administered by IV infusion | 85 |
| Total | 247 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 18 | 14 | 16 | 48 | 38 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Sponsor Decision | 6 | 4 | 10 | 33 | 32 |
| Overall Study | Withdrawal by Subject | 1 | 6 | 1 | 4 | 14 |
Baseline characteristics
| Characteristic | Part B1 Second Line Treatment | Part B2 Second Line Treatment | Part C Control First Line Treatment | Part A First Line Treatment | Part C Experimental First Line Treatment | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 12 Participants | 35 Participants | 9 Participants | 28 Participants | 93 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 16 Participants | 50 Participants | 16 Participants | 57 Participants | 154 Participants |
| Age, Continuous | 59.0 years STANDARD_DEVIATION 7.94 | 60.0 years STANDARD_DEVIATION 13.7 | 59.8 years STANDARD_DEVIATION 12.76 | 58.6 years STANDARD_DEVIATION 14.65 | 59.0 years STANDARD_DEVIATION 11.39 | 59.4 years STANDARD_DEVIATION 12.15 |
| Body Surface Area (BSA) | 1.8 m^2 STANDARD_DEVIATION 0.25 | 1.8 m^2 STANDARD_DEVIATION 0.26 | 1.8 m^2 STANDARD_DEVIATION 0.25 | 2.0 m^2 STANDARD_DEVIATION 0.23 | 1.8 m^2 STANDARD_DEVIATION 0.28 | 1.8 m^2 STANDARD_DEVIATION 0.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 5 Participants | 3 Participants | 1 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 26 Participants | 80 Participants | 22 Participants | 82 Participants | 232 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 18 Participants | 54 Participants | 1 Participants | 51 Participants | 138 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 28 Participants | 20 Participants | 30 Participants | 96 Participants |
| Region of Enrollment Germany | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 6 Participants | 10 Participants |
| Region of Enrollment South Korea | 14 Participants | 16 Participants | 51 Participants | 0 Participants | 49 Participants | 130 Participants |
| Region of Enrollment United States | 10 Participants | 12 Participants | 30 Participants | 25 Participants | 30 Participants | 107 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 21 Participants | 6 Participants | 26 Participants | 64 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 64 Participants | 19 Participants | 59 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 25 | 14 / 24 | 16 / 28 | 48 / 85 | 38 / 85 |
| other Total, other adverse events | 25 / 25 | 23 / 24 | 24 / 28 | 82 / 85 | 83 / 85 |
| serious Total, serious adverse events | 11 / 25 | 13 / 24 | 13 / 28 | 33 / 85 | 37 / 85 |
Outcome results
Primary
Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients
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.
Time frame: approximately 28 months
Population: In Parts A and B, 25 patients were enrolled in Part A and 53 patients were enrolled in Part B. The Safety population consisted of 25 patients in Part A and 52 patients in Part B, and the modified Intent-to-Treat (mITT) population consisted of 22 patients in Part A and 52 patients in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A First Line Treatment | Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | 25 Participants |
| Part B1 Second Line Treatment | Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | 24 Participants |
| Part B2 Second Line Treatment | Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients | 25 Participants |
Primary
Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy
PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first.
Time frame: approximately 30 months
Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX; Control group: Tislelizumab + CAPOX/FOLFOX
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy | 10.41 Months |
| Part B1 Second Line Treatment | Part C: Progression Free Survival (PFS) in G/GEJ DKK1 High and Overall Patients Treated With DKN-01 in Combination With Tislelizumab and Chemotherapy vs Tislelizumab and Chemotherapy as a First-line Therapy | 7.66 Months |
p-value: 0.967695% CI: [0.98, 2.05]Log Rank
Secondary
Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part A: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 95.5 percentage of patients |
Secondary
Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
Durable clinical benefit (DCB) is defined as the proportion of patients presenting a Duration of clinical benefit (DoCB) for ≥180 days from initiation of DKN-01. Patients who have a best overall response of PD or those with clinical benefit lasting \<180 days are not included.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part A: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 72.7 percentage of patients |
Secondary
Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
DoCB is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part A: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 11.9 months |
Secondary
Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
DoCR is defined as the time from initial complete response (CR) until radiographically documented progressive disease or death due to any cause, whichever is first.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part A: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 12.7 months |
Secondary
Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part A: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 10.0 months |
Secondary
Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy
Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) through radiological assessment of tumor response, based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Investigators were urged to have the same radiographic imaging modality used throughout the study for each subject (at baseline and at subsequent assessments) in order to provide uniformity of radiographic assessments.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part A: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab + CAPOX as a First-line Therapy | 72.7 percentage of patients |
Secondary
Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.
Time frame: approximately 28 months
Population: The mITT population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 19.7 months |
Secondary
Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy
For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part A: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy | 11.8 Months |
Secondary
Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
DCR is defined as the proportion of patients presenting with a best overall response (BOR) of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for a duration of at least 6 weeks from initiation of DKN-01, as assessed by the Investigator using RECIST v1.1.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 31.8 percentage of patients |
| Part B1 Second Line Treatment | Part B: Disease Control Rate (DCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 37.5 percentage of patients |
Secondary
Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
DCB rate is defined as the proportion of patients presenting a DoCB (Duration of clinical benefit) for ≥ 180 days from initiation of DKN-01, Patients who have a best overall response of PD or those with clinical benefit lasting \<180 days will not be included.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 18.2 percentage of patients |
| Part B1 Second Line Treatment | Part B: Durable Clinical Benefit (DCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 33.3 percentage of patients |
Secondary
Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
Duration of clinical benefit (DoCB) is defined as the time from the initiation of DKN-01 to the time of progressive disease or death due to any cause, whichever occurs first, for patients who had a BOR of CR, PR, or SD of ≥6 weeks.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience PD or death at the time of the analysis were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | NA months |
| Part B1 Second Line Treatment | Part B: Duration of Clinical Benefit (DoCB) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | NA months |
Secondary
Part B: Duration of Complete Response (DoCR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
Duration of complete response (DoCR) is defined as the time from initial CR until radiographically documented progressive disease or death due to any cause, whichever is first. No patients had a complete response (CR); therefore, the DoCR was not applicable.
Time frame: approximately 28 months
Secondary
Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
DoR is defined only for responders (patients with BOR of CR or PR) as the time from initial response until radiographically documented progressive disease or death due to any cause, whichever is earlier.
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01. Patients who do not experience progressive disease (PD) or death at the time of the analysis were censored. The median DoR was not reached in the 300 mg dose group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | NA months |
| Part B1 Second Line Treatment | Part B: Duration of Response (DoR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 5.6 months |
Secondary
Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Time frame: approximately 28 months
Population: The modified Intent-to-Treat (mITT) population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 18.2 percentage of patients |
| Part B1 Second Line Treatment | Part B: Objective Response Rate (ORR) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 25.0 percentage of patients |
Secondary
Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
Overall survival (OS) is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.
Time frame: approximately 28 months
Population: The mITT population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 8.2 months |
| Part B1 Second Line Treatment | Part B: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 7.7 months |
Secondary
Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy
For RECIST, PFS is defined as the time from first study drug dose (i.e., C1D1) to first radiographically documented progressive disease or death due to any cause.
Time frame: approximately 28 months
Population: The mITT population is defined as all patients who received more than one dose of DKN-01.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 1.4 months |
| Part B1 Second Line Treatment | Part B: Progression Free Survival (PFS) in G/GEJ Patients Treated With DKN-01 in Combination With Tislelizumab as a Second-line Therapy | 1.4 months |
Secondary
Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy.
PFS was measured from the date of randomization to the date of documented disease progression, based on investigator assessed radiologic review using RECIST v1.1, or death due to any cause, whichever occurred first. If the patient had not died, but there was no radiographic post-baseline tumor assessment, PFS was censored at the date of randomization. If there were radiographic post-baseline tumor assessments that verified lack of disease progression, PFS was censored at the most recent tumor assessment before the data cut-off or study withdrawal, whichever occurred first.
Time frame: approximately 30 months
Population: Intent-to-Treat (ITT): All patients randomized to treatment. Patients will be included in the treatment group assigned at randomization regardless of the actual treatment received. Experimental: DKK1+tislelizumab+(CAPOX/mFOLFOX6), Control: tislelizumab+(CAPOX/mFOLFOX6).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 7.43 Months |
| Part B1 Second Line Treatment | Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 11.14 Months |
| Part B2 Second Line Treatment | Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 7.66 Months |
| PFS All Patients, Part C Control | Part C: Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves PFS in Patients w/ Combined Positive Score (CPS) ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 10.41 Months |
p-value: 0.8679Log Rank
p-value: 0.9676Log Rank
95% CI: [0.74, 3.05]
95% CI: [0.98, 2.05]
Secondary
Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms.
To characterize the frequency of toxicity ≥Grade 3 treatment-related adverse events (TRAE) associated with each treatment arm: Control (tislelizumab in combination with chemotherapy regimen (CAPOX or mFOLFOX6) and Experimental (DKN-01 in combination with tislelizumab and chemotherapy regimen (CAPOX or mFOLFOX6))
Time frame: approximately 30 months
Population: 170 patients were randomized and 169 patients were treated with study medication: 84 in the Experimental group and 85 in the Control group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms. | 53 number of patients |
| Part B1 Second Line Treatment | Part C: Number of Patients With Toxicity ≥Grade 3 Treatment-related Adverse Events (TRAE) Associated With Each of the Treatment Arms. | 57 number of patients |
Secondary
Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy.
Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Risk difference (RD)(%) or ORR: Positive RD implies the exposure is associated with a higher probability of the outcome occurring. Negative RD indicates the exposure is associated with a lower probability of the outcome occurring.
Time frame: approximately 30 months
Population: Intent-to-Treat (ITT): All patients randomized to treatment. Patients will be included in the treatment group assigned at randomization regardless of the actual treatment received. Experimental: DKK1+tislelizumab+(CAPOX/mFOLFOX6), Control: tislelizumab+(CAPOX/mFOLFOX6).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 72.7 percentage |
| Part B1 Second Line Treatment | Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 63.6 percentage |
| Part B2 Second Line Treatment | Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 60 percentage |
| PFS All Patients, Part C Control | Part C: To Assess Whether the Addition of DKN-01 With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) Improves ORR in Patients With CPS ≥5 or CPS <5 Advanced DKK1-high and Overall G/GEJ Adenocarcinoma as a First-line Therapy. | 57.6 percentage |
p-value: 0.264995% CI: [-18.4, 33.6]Mantel Haenszel
p-value: 0.37995% CI: [-12.2, 16.9]Mantel Haenszel
Secondary
Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.
The duration of response (DoR) is defined only for responders (patients with a BOR of CR or PR) at the time from initial response (CR or PR) until radiographically documented progressive disease or death due to any cause, whichever is earlier. For ORR patient without PD or death, DoR is censored at the most recent tumor assessment before the data cutoff or study withdrawal, whichever occurs first.
Time frame: approximately 30 months
Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 12.06 months |
| Part B1 Second Line Treatment | Part C: To Estimate the Duration of Response (DoR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 6.24 months |
Secondary
Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.
Objective Response Rate (ORR) is defined as the proportion of patients achieving best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator using RECIST v1.1. Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX
Time frame: approximately 30 months
Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A First Line Treatment | Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 57.6 percentage of patients |
| Part B1 Second Line Treatment | Part C: To Estimate the Objective Response Rate (ORR) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 60 percentage of patients |
p-value: 0.379995% CI: [-12.2, 16.9]Cochran-Mantel-Haenszel
Secondary
Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy.
Overall survival (OS) OS is defined as the time from the date of randomization to death due to any cause. For a patient who is not known to have died by the end of study follow-up, observation of OS is censored at the date the patient was last known to be alive (i.e., date of last contact). Patients lacking data beyond the day of randomization is censored at the date of randomization (i.e., OS duration of 1 day).
Time frame: approximately 30 months
Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A First Line Treatment | Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 18.76 months |
| Part B1 Second Line Treatment | Part C: To Estimate the Overall Survival (OS) in DKK1-high G/GEJ Adenocarcinoma Patients Treated With DKN-01 in Combination With Tislelizumab + Chemotherapy Regimen (CAPOX or mFOLFOX6) as a First-line Therapy. | 15.38 months |