Trial Outcomes & Findings for A Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy in Patients With Gastric or Gastroesophageal Cancer (NCT NCT04363801)

Last Updated: 2025-10-09

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

247 participants

Primary outcome timeframe

approximately 28 months

Results posted on

2025-10-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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	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 Dickkopf-1 (DKK1)-high (H-score ≥ 35) gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±human epidermal growth factor receptor 2 (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	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	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	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
Overall Study STARTED	25	24	28	85	85
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	25	24	28	85	85

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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 Dickkopf-1 (DKK1)-high (H-score ≥ 35) gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (pre-screen biopsy) and must have had only 1 prior systemic therapy for locally advanced/metastatic disease (platinum + fluoropyrimidine-based therapy; ±human epidermal growth factor receptor 2 (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	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	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	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
Overall Study Death	18	14	16	48	38
Overall Study Withdrawal by Subject	1	6	1	4	14
Overall Study Sponsor Decision	6	4	10	33	32
Overall Study Lost to Follow-up	0	0	1	0	1

Baseline Characteristics

Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A First Line Treatment n=25 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	Part B2 Second Line Treatment n=28 Participants 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	Part C Control First Line Treatment n=85 Participants 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	Part C Experimental First Line Treatment n=85 Participants 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	Total n=247 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=25 Participants	0 Participants n=24 Participants	0 Participants n=28 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	0 Participants n=247 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=25 Participants	15 Participants n=24 Participants	16 Participants n=28 Participants	50 Participants n=85 Participants	57 Participants n=85 Participants	154 Participants n=247 Participants
Age, Categorical >=65 years	9 Participants n=25 Participants	9 Participants n=24 Participants	12 Participants n=28 Participants	35 Participants n=85 Participants	28 Participants n=85 Participants	93 Participants n=247 Participants
Age, Continuous	58.6 years STANDARD_DEVIATION 14.65 • n=25 Participants	59.0 years STANDARD_DEVIATION 7.94 • n=24 Participants	60.0 years STANDARD_DEVIATION 13.70 • n=28 Participants	59.8 years STANDARD_DEVIATION 12.76 • n=85 Participants	59.0 years STANDARD_DEVIATION 11.39 • n=85 Participants	59.4 years STANDARD_DEVIATION 12.15 • n=247 Participants
Sex: Female, Male Female	6 Participants n=25 Participants	4 Participants n=24 Participants	7 Participants n=28 Participants	21 Participants n=85 Participants	26 Participants n=85 Participants	64 Participants n=247 Participants
Sex: Female, Male Male	19 Participants n=25 Participants	20 Participants n=24 Participants	21 Participants n=28 Participants	64 Participants n=85 Participants	59 Participants n=85 Participants	183 Participants n=247 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=25 Participants	2 Participants n=24 Participants	1 Participants n=28 Participants	5 Participants n=85 Participants	1 Participants n=85 Participants	12 Participants n=247 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=25 Participants	22 Participants n=24 Participants	26 Participants n=28 Participants	80 Participants n=85 Participants	82 Participants n=85 Participants	232 Participants n=247 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants	0 Participants n=24 Participants	1 Participants n=28 Participants	0 Participants n=85 Participants	2 Participants n=85 Participants	3 Participants n=247 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=24 Participants	0 Participants n=28 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	0 Participants n=247 Participants
Race (NIH/OMB) Asian	1 Participants n=25 Participants	14 Participants n=24 Participants	18 Participants n=28 Participants	54 Participants n=85 Participants	51 Participants n=85 Participants	138 Participants n=247 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=25 Participants	0 Participants n=24 Participants	0 Participants n=28 Participants	0 Participants n=85 Participants	0 Participants n=85 Participants	1 Participants n=247 Participants
Race (NIH/OMB) Black or African American	1 Participants n=25 Participants	0 Participants n=24 Participants	0 Participants n=28 Participants	0 Participants n=85 Participants	2 Participants n=85 Participants	3 Participants n=247 Participants
Race (NIH/OMB) White	20 Participants n=25 Participants	9 Participants n=24 Participants	9 Participants n=28 Participants	28 Participants n=85 Participants	30 Participants n=85 Participants	96 Participants n=247 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants	0 Participants n=24 Participants	0 Participants n=28 Participants	0 Participants n=85 Participants	1 Participants n=85 Participants	1 Participants n=247 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=25 Participants	1 Participants n=24 Participants	1 Participants n=28 Participants	3 Participants n=85 Participants	1 Participants n=85 Participants	8 Participants n=247 Participants
Region of Enrollment South Korea	0 Participants n=25 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	14 Participants n=24 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	16 Participants n=28 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	51 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	49 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	130 Participants n=247 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.
Region of Enrollment United States	25 Participants n=25 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	10 Participants n=24 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	12 Participants n=28 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	30 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	30 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	107 Participants n=247 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.
Region of Enrollment Germany	0 Participants n=25 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	0 Participants n=24 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	0 Participants n=28 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	4 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	6 Participants n=85 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.	10 Participants n=247 Participants • Descriptive statistics were used to summarize demographics and Baseline characteristics for the Safety and mITT populations. In addition, select Baseline characteristics were analyzed with respect to geographic region, i.e., USA versus The Republic of South Korea.
Body Surface Area (BSA)	2.0 m^2 STANDARD_DEVIATION 0.23 • n=25 Participants • Some subject data in Part C not available for analysis of BSA	1.8 m^2 STANDARD_DEVIATION 0.25 • n=24 Participants • Some subject data in Part C not available for analysis of BSA	1.8 m^2 STANDARD_DEVIATION 0.26 • n=28 Participants • Some subject data in Part C not available for analysis of BSA	1.8 m^2 STANDARD_DEVIATION 0.25 • n=83 Participants • Some subject data in Part C not available for analysis of BSA	1.8 m^2 STANDARD_DEVIATION 0.28 • n=84 Participants • Some subject data in Part C not available for analysis of BSA	1.8 m^2 STANDARD_DEVIATION 0.27 • n=244 Participants • Some subject data in Part C not available for analysis of BSA

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=25 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	Part B2 Second Line Treatment n=28 Participants 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	PFS All Patients, Part C Control 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
Part A and B: Safety and Tolerability of DKN-01 in G/GEJ Patients	25 Participants	24 Participants	25 Participants	—

PRIMARY outcome

Timeframe: approximately 30 months

Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX; Control group: Tislelizumab + CAPOX/FOLFOX

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=85 Participants 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	Part B1 Second Line Treatment n=85 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 7.75 to 13.86	7.66 Months Interval 6.87 to 9.49	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 49.8 to 89.3	—	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 5.19 to 40.3	25.0 percentage of patients Interval 9.77 to 46.7	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=16 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 5.1 to 19.2	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=1 Participants 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	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	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	PFS All Patients, Part C Control 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
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 95% Confidence Interval not calculable for a single participant	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 7.9 to The upper confidence limit (UCL) for the 50th percentile is defined as the first time at which the UCL for S(t) (based on a ln(-lnS(t)) transformation) is less than or equal too 1-50/100=0.5. There is never an observed failure time for which the upper bound of the confidence interval (CI) for the Kaplan Meier (KM) estimate (calculated using the Greenwood's method, different from ln(-lnS(t)) transformation) is less than 0.5, due to lack of events \& sample size.	—	—	—

SECONDARY outcome

Timeframe: approximately 28 months

Population: The mITT population is defined as all patients who received more than one dose of DKN-01.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	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	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	PFS All Patients, Part C Control 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
Part A: Overall Survival (OS) in G/GEJ Patients Treated With DKN-01 With Tislelizumab + CAPOX as a First-line Therapy	19.7 months Interval 15.3 to The upper confidence limit for the 50th percentile is defined as the first time at which the upper confidence limit for S(t) (based on a ln(-lnS(t)) transformation) is less than or equal to 1-50/100 =0.5. There is never an observed failure time for which the upper bound of the confidence interval for the KM estimate (calculated using the Greenwood's method, which is different from the ln(-lnS(t)) transformation above) is less than 0.5, due to lack of events and sample size.	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=20 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 8.2 to The upper confidence limit for the 50th percentile is defined as the first time at which the upper confidence limit for S(t) (based on a ln(-lnS(t)) transformation) is less than or equal to 1-50/100 =0.5. There is never an observed failure time for which the upper bound of the confidence interval for the KM estimate (calculated using the Greenwood's method, which is different from the ln(-lnS(t)) transformation above) is less than 0.5, due to lack of events and sample size.	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 49.8 to 89.3	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	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	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	PFS All Patients, Part C Control 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
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 Interval 77.2 to 99.9	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=4 Participants 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	Part B1 Second Line Treatment n=6 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 1.5 to insufficient number of participants with events	5.6 months Interval 2.3 to insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: approximately 28 months

Population: The mITT population is defined as all patients who received more than one dose of DKN-01.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 1.3 to 2.3	1.4 months Interval 1.2 to 6.8	—	—

SECONDARY outcome

Timeframe: approximately 28 months

Population: The mITT population is defined as all patients who received more than one dose of DKN-01.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 2.6 to 18.0	7.7 months Interval 3.8 to insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=4 Participants 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	Part B1 Second Line Treatment n=8 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 11.8 to insufficient number of participants with events	NA months Interval 6.8 to insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 5.19 to 40.3	33.3 percentage of patients Interval 15.6 to 55.3	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=24 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 13.9 to 54.9	37.5 percentage of patients Interval 18.8 to 59.4	—	—

SECONDARY outcome

Timeframe: approximately 30 months

Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX

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

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=85 Participants 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	Part B1 Second Line Treatment n=85 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 46.4 to 68.3	60 percentage of patients Interval 48.8 to 70.5	—	—

SECONDARY outcome

Timeframe: approximately 30 months

Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX

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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=49 Participants 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	Part B1 Second Line Treatment n=51 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 7.56 to 16.99	6.24 months Interval 5.06 to 8.54	—	—

SECONDARY outcome

Timeframe: approximately 30 months

Population: Experimental group: Sirexatamab + tislelizumab + CAPOX/FOLFOX, Control group: Tislelizumab + CAPOX/FOLFOX

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).

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=85 Participants 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	Part B1 Second Line Treatment n=85 Participants 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	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	PFS All Patients, Part C Control 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
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 Interval 14.0 to The upper confidence limit for the 50th percentile is defined as the first time at which the upper confidence limit for S(t) (based on a ln(-lnS(t)) transformation) is less than or equal to 1-50/100 =0.5. There is never an observed failure time for which the upper bound of the confidence interval for the KM estimate (calculated using the Greenwood's method, which is different from the ln(-lnS(t)) transformation above) is less than 0.5, due to lack of events and sample size.	15.38 months Interval 13.4 to 19.45	—	—

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=22 Participants 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	Part B1 Second Line Treatment n=22 Participants 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	Part B2 Second Line Treatment n=85 Participants 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	PFS All Patients, Part C Control n=85 Participants 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
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 Interval 5.65 to 7.75	11.14 Months Interval 7.46 to 14.42	7.66 Months Interval 6.87 to 9.49	10.41 Months Interval 7.75 to 13.86

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=16 Participants 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	Part B1 Second Line Treatment n=14 Participants 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	Part B2 Second Line Treatment n=51 Participants 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	PFS All Patients, Part C Control n=49 Participants 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
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 Interval 49.8 to 89.3	63.6 percentage Interval 40.7 to 82.8	60 percentage Interval 48.8 to 70.5	57.6 percentage Interval 46.4 to 68.3

SECONDARY outcome

Timeframe: 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.

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))

Outcome measures

Outcome measures
Measure	Part A First Line Treatment n=85 Participants 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	Part B1 Second Line Treatment n=84 Participants 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	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	PFS All Patients, Part C Control 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
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	57 number of patients	—	—

Adverse Events

Part A First Line Treatment

Serious events: 11 serious events

Other events: 25 other events

Deaths: 18 deaths

Part B1 Second Line Treatment

Serious events: 13 serious events

Other events: 23 other events

Deaths: 14 deaths

Part B2 Second Line Treatment

Serious events: 13 serious events

Other events: 24 other events

Deaths: 16 deaths

Part C Control First Line Treatment

Serious events: 33 serious events

Other events: 82 other events

Deaths: 48 deaths

Part C Experimental First Line Treatment

Serious events: 37 serious events

Other events: 83 other events

Deaths: 38 deaths

Serious adverse events

Serious adverse events
Measure	Part A First Line Treatment n=25 participants at risk 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	Part B1 Second Line Treatment n=24 participants at risk 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	Part B2 Second Line Treatment n=28 participants at risk 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	Part C Control First Line Treatment n=85 participants at risk 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	Part C Experimental First Line Treatment n=85 participants at risk 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
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Blood and lymphatic system disorders Neutropenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Acute myocardial infarction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Angina pectoris	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Atrial fibrillation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Cardiac disorders Cardiac arrest	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Cardiogenic shock	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Eosinophilic myocarditis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Endocrine disorders Adrenal insufficiency	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Ophthalmoplegia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Abdominal distension	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Abdominal incarcerated hernia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Abdominal pain	0.00% 0/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	14.3% 4/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Gastrointestinal disorders Ascites	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Constipation	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Dysphagia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Entercolitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Enteritis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Gastric perforation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Ileus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Gastrointestinal disorders Immune-mediated enterocolitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Melaena	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Nausea	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Obstruction gastric	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Gastrointestinal disorders Pancreatitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Gastrointestinal disorders Pancreatitis acute	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Subileus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Vomiting	4.0% 1/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
General disorders Asthenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Chest pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Fatigue	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders General physical health deterioration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Multiple organ dysfunction syndrome	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Pyrexia	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Hepatobiliary disorders Biliary obstruction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Hepatobiliary disorders Cholangitis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Cholecystitis acute	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Hepatobiliary disorders Hepatitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Infections and infestations COVID-19	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Infections and infestations Norovirus infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Pneumonia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Infections and infestations Sepsis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Infections and infestations Septic shock	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Fall	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Hip fracture	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Alanine aminotransferase increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Aspartate aminotransferase increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Blood bilirubin increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Blood calcium decreased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Hemoglobin decreased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Liver function test increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Decreased appetite	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Dehydration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Failure to thrive	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Muscular weakness	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Cerebral infarction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Cerebrovascular accident	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Syncope	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Psychiatric disorders Delirium	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Acute kidney injury	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Renal and urinary disorders Chronic kidney disease	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Hydronephrosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Cough	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Hepatic failure	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Hepatobiliary disorders Immune-mediated hepatitis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Biliary tract infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Spontaneous bacterial peritonitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Abdominal pain lower	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months

Other adverse events

Other adverse events
Measure	Part A First Line Treatment n=25 participants at risk 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	Part B1 Second Line Treatment n=24 participants at risk 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	Part B2 Second Line Treatment n=28 participants at risk 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	Part C Control First Line Treatment n=85 participants at risk 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	Part C Experimental First Line Treatment n=85 participants at risk 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
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Nausea	76.0% 19/25 • Up to 30 months	29.2% 7/24 • Up to 30 months	17.9% 5/28 • Up to 30 months	31.8% 27/85 • Up to 30 months	36.5% 31/85 • Up to 30 months
Gastrointestinal disorders Diarrhoea	72.0% 18/25 • Up to 30 months	16.7% 4/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	27.1% 23/85 • Up to 30 months	27.1% 23/85 • Up to 30 months
Gastrointestinal disorders Constipation	48.0% 12/25 • Up to 30 months	20.8% 5/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	35.3% 30/85 • Up to 30 months	24.7% 21/85 • Up to 30 months
Gastrointestinal disorders Vomiting	44.0% 11/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	20.0% 17/85 • Up to 30 months	25.9% 22/85 • Up to 30 months
Gastrointestinal disorders Abdominal pain	24.0% 6/25 • Up to 30 months	33.3% 8/24 • Up to 30 months	17.9% 5/28 • Up to 30 months	21.2% 18/85 • Up to 30 months	11.8% 10/85 • Up to 30 months
Gastrointestinal disorders Stomatitis	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	16.5% 14/85 • Up to 30 months	11.8% 10/85 • Up to 30 months
Gastrointestinal disorders Dry mouth	20.0% 5/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Gastrointestinal disorders Dysphagia	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Dyspepsia	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	12.9% 11/85 • Up to 30 months	8.2% 7/85 • Up to 30 months
Gastrointestinal disorders Abdominal distension	12.0% 3/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Gastrointestinal disorders Abdominal pain upper	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Ascites	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Gastrointestinal disorders Gastrooesophageal reflux disease	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Haemorrhoids	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Retching	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Flatulence	4.0% 1/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Eructation	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Proctalgia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Anal haemorrhage	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Enteritis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Gingival bleeding	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Glossodynia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Mouth ulceration	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Oesophageal obstruction	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Oral dysaesthesia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Pancreatitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Gastrointestinal disorders Malignant gastrointestinal obstruction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Obstruction gastric	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Gastrointestinal disorders Oesophagitis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Oral pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Gastrointestinal disorders Abdominal discomfort	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Cheilitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Gastric ulcer	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Gastritis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Gingival pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Duodenal obstruction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Enterocolitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Haematemesis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Inguinal hernia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Lip pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Mucous stools	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Oesophageal food impaction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Tongue discolouration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Toothache	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Gastrointestinal disorders Abdominal tenderness	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Intestinal obstruction	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Gastrointestinal disorders Oral discharge	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Neutrophil count decreased	40.0% 10/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	43.5% 37/85 • Up to 30 months	36.5% 31/85 • Up to 30 months
Investigations Platelet count decreased	28.0% 7/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	40.0% 34/85 • Up to 30 months	21.2% 18/85 • Up to 30 months
Investigations Aspartate aminotransferase increased	12.0% 3/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	24.7% 21/85 • Up to 30 months	16.5% 14/85 • Up to 30 months
Investigations Weight decreased	20.0% 5/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	15.3% 13/85 • Up to 30 months	18.8% 16/85 • Up to 30 months
Investigations Blood bilirubin increased	16.0% 4/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	17.9% 5/28 • Up to 30 months	10.6% 9/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Investigations Alanine aminotransferase increased	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	16.5% 14/85 • Up to 30 months	12.9% 11/85 • Up to 30 months
Investigations Lymphocyte count decreased	12.0% 3/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations White blood cell count decreased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	10.6% 9/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Investigations Blood creatinine increased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Troponin T increased	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Amylase increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	8.2% 7/85 • Up to 30 months
Investigations Lipase increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Investigations Blood alkaline phosphatase increased	0.00% 0/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Investigations Blood lactate dehydrogenase increased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations International normalised ratio increased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Investigations Blood creatine phosphokinase increased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Investigations Blood thyroid stimulating hormone increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Investigations Ejection fraction decreased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Electrocardiogram ST segment abnormal	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Weight increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Investigations Human chorionic gonadotropin increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Creatinine renal clearance decreased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Investigations Electrocardiogram QT prolonged	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Blood creatine increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Troponin I increased	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations Urine output decreased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Investigations C-reactive protein increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Investigations White blood cell count increased	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Decreased appetite	40.0% 10/25 • Up to 30 months	16.7% 4/24 • Up to 30 months	14.3% 4/28 • Up to 30 months	35.3% 30/85 • Up to 30 months	30.6% 26/85 • Up to 30 months
Metabolism and nutrition disorders Hypokalaemia	28.0% 7/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	10.6% 9/85 • Up to 30 months
Metabolism and nutrition disorders Dehydration	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	17.9% 5/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Metabolism and nutrition disorders Hypoalbuminaemia	4.0% 1/25 • Up to 30 months	16.7% 4/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Metabolism and nutrition disorders Hyperglycaemia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	9.4% 8/85 • Up to 30 months	8.2% 7/85 • Up to 30 months
Metabolism and nutrition disorders Hyponatraemia	8.0% 2/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Metabolism and nutrition disorders Hypocalcaemia	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Hypophosphataemia	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Abnormal loss of weight	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Metabolism and nutrition disorders Hypomagnesaemia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Food aversion	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Hypercalcaemia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Metabolism and nutrition disorders Iron deficiency	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Hypophagia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Peripheral sensory neuropathy	44.0% 11/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	37.6% 32/85 • Up to 30 months	41.2% 35/85 • Up to 30 months
Nervous system disorders Neuropathy peripheral	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	17.6% 15/85 • Up to 30 months	24.7% 21/85 • Up to 30 months
Nervous system disorders Headache	28.0% 7/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	9.4% 8/85 • Up to 30 months	12.9% 11/85 • Up to 30 months
Nervous system disorders Dizziness	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	11.8% 10/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Nervous system disorders Dysgeusia	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Nervous system disorders Paraesthesia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	9.4% 8/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Nervous system disorders Peripheral motor neuropathy	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Nervous system disorders Presyncope	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Nervous system disorders Dysaesthesia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Lethargy	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Neuralgia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Tremor	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Cognitive disorder	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Nervous system disorders Syncope	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Nervous system disorders Polyneuropathy	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Cerebral infarction	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Disturbance in attention	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Nervous system disorders Hypoaesthesia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Nervous system disorders Memory impairment	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Nervous system disorders Taste disorder	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Nervous system disorders Vocal cord paresis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Fatigue	68.0% 17/25 • Up to 30 months	29.2% 7/24 • Up to 30 months	21.4% 6/28 • Up to 30 months	27.1% 23/85 • Up to 30 months	29.4% 25/85 • Up to 30 months
General disorders Oedema peripheral	24.0% 6/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	8.2% 7/85 • Up to 30 months
General disorders Pyrexia	8.0% 2/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	24.7% 21/85 • Up to 30 months	15.3% 13/85 • Up to 30 months
General disorders Asthenia	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	10.6% 9/85 • Up to 30 months	10.6% 9/85 • Up to 30 months
General disorders Mucosal inflammation	12.0% 3/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	10.6% 9/85 • Up to 30 months
General disorders Chills	12.0% 3/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
General disorders Temperature intolerance	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Influenza like illness	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Medical device pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Non-cardiac chest pain	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
General disorders Peripheral swelling	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Discomfort	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Infusion site pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Medical device site erosion	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Pain	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
General disorders Generalised oedema	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Chest pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Early satiety	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
General disorders Malaise	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Cyst	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Face oedema	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Feeling cold	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Hernia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
General disorders Infusion site extravasation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Infusion site rash	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
General disorders Oedema	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	40.0% 10/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	20.0% 17/85 • Up to 30 months	20.0% 17/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash	16.0% 4/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	8.2% 7/85 • Up to 30 months	11.8% 10/85 • Up to 30 months
Skin and subcutaneous tissue disorders Pruritus	4.0% 1/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	14.3% 4/28 • Up to 30 months	10.6% 9/85 • Up to 30 months	11.8% 10/85 • Up to 30 months
Skin and subcutaneous tissue disorders Dry skin	20.0% 5/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Skin and subcutaneous tissue disorders Rash maculo-papular	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	12.9% 11/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Skin and subcutaneous tissue disorders Blister	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Hyperhidrosis	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Skin and subcutaneous tissue disorders Erythema	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Hyperkeratosis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Skin and subcutaneous tissue disorders Dermal cyst	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Ecchymosis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Eczema	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Ingrowing nail	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Onychoclasis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Onychomadesis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Photosensitivity reaction	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Psoriasis	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin fissures	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Skin and subcutaneous tissue disorders Lichenoid keratosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Nail bed inflammation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Penile ulceration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin erosion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Skin odour abnormal	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Dyspnoea	24.0% 6/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	12.9% 11/85 • Up to 30 months	11.8% 10/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Cough	20.0% 5/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	9.4% 8/85 • Up to 30 months	10.6% 9/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Hiccups	4.0% 1/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Dysphonia	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Productive cough	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Aspiration	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Dyspnoea paroxysmal nocturnal	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/25 • Up to 30 months	20.8% 5/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Laryngospasm	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Arthralgia	28.0% 7/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	9.4% 8/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Back pain	16.0% 4/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	10.6% 9/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Myalgia	4.0% 1/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Pain in extremity	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Muscle spasms	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	4.7% 4/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Muscular weakness	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Pain in jaw	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Arthritis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Neck pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Sacral pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Trismus	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations COVID-19	12.0% 3/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	8.2% 7/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Infections and infestations Pneumonia	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	8.2% 7/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Infections and infestations Urinary tract infection	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Oral candidiasis	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Upper respiratory tract infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Infections and infestations Otitis media	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Nasopharyngitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Infections and infestations Sepsis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Bronchitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Rash pustular	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Bacteraemia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Candida infection	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Infections and infestations Conjunctivitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Laryngitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Onychomycosis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Oral herpes	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Sinusitis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Viraemia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Vulvovaginal mycotic infection	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Influenza	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Body tinea	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Cystitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Device related infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Fungal skin infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Gastroenteritis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Gastroenteritis viral	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Gastrointestinal infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Gingivitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Herpes zoster	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Hordeolum	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Parotitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Penile infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Pulmonary tuberculosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Respiratory syncytial virus infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Rhinitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Vaginal infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Viral infection	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Infections and infestations Paronychia	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Infections and infestations Pneumonia aspiration	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Blood and lymphatic system disorders Anaemia	28.0% 7/25 • Up to 30 months	25.0% 6/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	28.2% 24/85 • Up to 30 months	25.9% 22/85 • Up to 30 months
Blood and lymphatic system disorders Neutropenia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	7.1% 6/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Blood and lymphatic system disorders Leukocytosis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Blood and lymphatic system disorders Thrombocytopenia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Blood and lymphatic system disorders Leukopenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Blood and lymphatic system disorders Lymphopenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Blood and lymphatic system disorders Iron deficiency	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	16.5% 14/85 • Up to 30 months	8.2% 7/85 • Up to 30 months
Injury, poisoning and procedural complications Fall	16.0% 4/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Injury, poisoning and procedural complications Procedural pain	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Arthropod bite	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Foreign body in eye	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Limb injury	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Muscle strain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Skin abrasion	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Tendon injury	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Thermal burn	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Vascular access site pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Eyelid injury	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Injury, poisoning and procedural complications Contusion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Hand fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Skin injury	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Injury, poisoning and procedural complications Skin laceration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Injury, poisoning and procedural complications Wound	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Vision blurred	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Visual impairment	12.0% 3/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Dry eye	8.0% 2/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Eye disorders Dermatochalasis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Eye pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Lacrimation increased	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Photopsia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Vitreous floaters	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Retinal haemorrhage	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Eye disorders Retinopathy	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Cataract	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Retinal exudates	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Corneal erosion	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Detachment of retinal pigment epithelium	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Diabetic retinopathy	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Dry age-related macular degeneration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Eye pruritus	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Hyalosis asteroid	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Keratitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Macular degeneration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Ocular hyperaemia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Periorbital oedema	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Pterygium	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Retinal degeneration	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Retinal drusen	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Subretinal fluid	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Eye disorders Uveitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Eye disorders Xerophthalmia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Vascular disorders Hypotension	8.0% 2/25 • Up to 30 months	12.5% 3/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Vascular disorders Deep vein thrombosis	12.0% 3/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Vascular disorders Embolism	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Vascular disorders Hypertension	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Vascular disorders Superficial vein thrombosis	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Vascular disorders Flushing	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	3.5% 3/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Vascular disorders Aortic thrombosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Vascular disorders Hot flush	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Psychiatric disorders Insomnia	16.0% 4/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	10.7% 3/28 • Up to 30 months	9.4% 8/85 • Up to 30 months	7.1% 6/85 • Up to 30 months
Psychiatric disorders Depression	8.0% 2/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Psychiatric disorders Confusional state	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Psychiatric disorders Anxiety	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Psychiatric disorders Mental status changes	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Psychiatric disorders Delirium	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Psychiatric disorders Adjustment disorder with anxiety	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Psychiatric disorders Restlessness	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Haematuria	8.0% 2/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Renal and urinary disorders Pollakiuria	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Renal and urinary disorders Proteinuria	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Renal and urinary disorders Dysuria	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Renal and urinary disorders Urinary retention	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Hydronephrosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Renal and urinary disorders Acute kidney injury	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Calculus urinary	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Chromaturia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Glycosuria	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Micturition urgency	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Renal pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Renal and urinary disorders Urinary tract pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Renal and urinary disorders Urine odour abnormal	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Palpitations	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Sinus tachycardia	4.0% 1/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Arteriosclerosis coronary artery	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Atrial fibrillation	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Left ventricular failure	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Sinus arrhythmia	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Tricuspid valve incompetence	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Tachycardia	0.00% 0/25 • Up to 30 months	8.3% 2/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Atrial flutter	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Bradycardia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Left ventricular dysfunction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Pericardial effusion	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Sinus bradycardia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Cardiac disorders Sinus node dysfunction	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Cardiac disorders Supraventricular tachycardia	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Endocrine disorders Hypothyroidism	12.0% 3/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	7.1% 2/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	5.9% 5/85 • Up to 30 months
Endocrine disorders Hyperthyroidism	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	3.5% 3/85 • Up to 30 months
Endocrine disorders Adrenal insufficiency	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Ear and labyrinth disorders Tinnitus	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	5.9% 5/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Ear and labyrinth disorders Deafness	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Ear and labyrinth disorders Ear pain	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Ear and labyrinth disorders Hypoacusis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	4.7% 4/85 • Up to 30 months
Ear and labyrinth disorders Vertigo	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Immune system disorders Hypersensitivity	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	2.4% 2/85 • Up to 30 months
Immune system disorders Seasonal allergy	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Immune system disorders Drug hypersensitivity	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Hepatobiliary disorders Cholangitis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Hepatic failure	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	3.6% 1/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Hepatobiliary disorders Hepatitis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	2.4% 2/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Bile duct stenosis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Cholestasis	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Reproductive system and breast disorders Pruritus genital	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Reproductive system and breast disorders Pelvic pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	1.2% 1/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	4.0% 1/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/25 • Up to 30 months	0.00% 0/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	1.2% 1/85 • Up to 30 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/25 • Up to 30 months	4.2% 1/24 • Up to 30 months	0.00% 0/28 • Up to 30 months	0.00% 0/85 • Up to 30 months	0.00% 0/85 • Up to 30 months

Additional Information

Douglas Onsi / President and CEO

Leap Therapeutics, Inc.

Phone: 617-218-1116

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At least 45 days prior to submission for Publication, Institution submits proposed Publication to Sponsor. Review Period for abstracts/poster presentations is 30 days. Sponsor may notify Institution in writing that patent applications will be filed and publication may be deferred up to 60 days. If Publication has Sponsor Confidential Information (CI) \& Sponsor requests Institution to delete CI, Institution agrees to delete CI if it does not preclude the accurate interpretation of Study results.
Publication restrictions are in place

Restriction type: OTHER