Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736
Brief summary
This is a randomized, multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab, MEDI4736 monotherapy or tremelimumab monotherapy in participants with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma.
Interventions
BIOLOGICALMEDI4736 + tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.
BIOLOGICALMEDI4736
MEDI4736 will be administered by IV infusion.
BIOLOGICALTremelimumab
Tremelimumab will be administered by IV infusion.
BIOLOGICALMEDI4736+tremelimumab
MEDI4736 will be administered by IV infusion in combination with tremelimumab.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female participants 2. 18 years and older 3. Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma 4. Participants must have received and have progressed, or are refractory to standard regimens 5. Participants must have at least one lesion amenable to biospy
Exclusion criteria
1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment 2. Previous immunotherapy 3. Concurrent or prior use of immunosuppressive medication with 14 days 4. Active or prior documented autoimmune or inflammatory disease within 3 years with some exceptions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b | From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab | A DLT was defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab). The DLTs are: any Grade 4 immune-related adverse event (irAE), any Grade \>=3 non-irAE, \>= Grade 3 colitis, Grade 3 or 4 noninfectious pneumonitis irrespective of duration, Grade 2 pneumonitis, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN. Immune-related AEs are defined as AEs of an immune nature (ie, inflammatory) in the absence of a clear alternative etiology. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine. |
| Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight. |
| Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG. |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b | Baseline (Day 1) | The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented. |
| Percentage of Participants With Objective Response (OR) in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. |
| Progression Free Survival at 6 (PFS-6) Month in Phase 2 | From Day 1 upto 6 months | The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight. |
| Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG. |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | Baseline (Day 1) | The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented. |
| Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | From Day 1 up to 16 weeks | The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study. |
| Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | From Day 1 up to 24 weeks | The disease control rate at 24 weeks was defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study. |
| Duration of Response (DoR) in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | The DoR was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression according to RECIST v1.1 that occurred subsequently after response or death due to any cause, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline. Kaplan Meier method was used to evaluate DoR. |
| Time to Response (TTR) in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | TTR: time from date of randomization of participants for Arm A, B, and C or date of first dose of study drug for Arm D and Arm E until first documented OR per RECIST v1.1. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization/date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in SOD of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD; PD: at least 20% increase in SOD of target lesions from smallest sum (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method used to evaluate TTR. |
| Duration of Stable Disease in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | The DSD was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5 mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD. |
| Percentage of Participants With Objective Response in Phase 1b | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization of participants or date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. |
| Progression Free Survival in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | The PFS was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study treatment for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS. |
| Progression Free Survival at 9 Month (PFS-9) in Phase 2 | From Day 1 up to 9 months | The PFS-9 is the 9-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 9 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, C participants or the date of first dose of study drug for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS. |
| Overall Survival (OS) in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until death due to any cause. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS. |
| Overall Survival at 12 Months in Phase 2 | From Day 1 up to 12 months | The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until 12 months. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS and 95% confidence interval. |
| Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2 | Day 1 through Day 30 post EOT (approximately 4 years and one month) | Percentage of participants with OR with positive IFN-γ gene expression is reported. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. |
| Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2 | Day 1 through Day 30 post EOT (approximately 4 years and one month) | Percentage of participants with PFS at 6 month with positive IFN-γ gene expression is reported. The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6. |
| Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | Day 1 through Day 30 post EOT (approximately 4 years and one month) | Percentage of participants with objective response in Phase 2 by programmed death-ligand (PD-L1) status is reported. PD-L1 is a protein that may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. It plays a role in regulating the immune response against some types of cancers and therefore, is the target for some anticancer drugs. PD-L1 status was based on the percentage of tumor cells from baseline tumor tissue samples with PD-L1 membrane staining: PD-L1 high if \>= 1% tumor cells (better response), PD-L1 low/neg if \< 1% tumor cells (low response). |
| Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. |
| Duration of Stable Disease (DSD) in Phase 1b | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | The DSD was defined as the time from the date of first dose of study treatment for Phase 1b until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD. |
| Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b | From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month) | Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. |
| Percentage of Participants With Disease Control at 16 Weeks in Phase 1b | From Day 1 up to 16 weeks | The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study. |
| Percentage of Participants With Disease Control at 24 Weeks in Phase 1b | From Day 1 up to 24 weeks | The disease control rate at 24 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study. |
| Progression Free Survival at 6 Month in Phase 1b | From Day 1 upto 6 months | The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Phase 1b participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Day 1 up to 90 days after the last dose (approximately 4 years and one month) | Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine. |
Countries
Canada, Japan, Singapore, South Korea, Taiwan, United States
Participant flow
Recruitment details
The study was conducted in the United States of America, Japan, Korea, Taiwan and Singapore between 31Mar2015 and 29Apr2019.
Pre-assignment details
A total of 114 participants were randomized in the study, out of which 113 participants received study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses). | 6 |
| Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses). | 27 |
| Phase 2 Arm B-M10 mg/kg (Q2W) Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses). | 24 |
| Phase 2 Arm C-T10 mg/kg (Q4W) Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses). | 12 |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses). | 25 |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses). | 19 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 23 | 21 | 7 | 21 | 13 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Other | 0 | 4 | 0 | 2 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Phase 2 Arm B-M10 mg/kg (Q2W) | Phase 2 Arm C-T10 mg/kg (Q4W) | Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.0 Years STANDARD_DEVIATION 12.7 | 60.4 Years STANDARD_DEVIATION 13.5 | 59.8 Years STANDARD_DEVIATION 12 | 52.3 Years STANDARD_DEVIATION 16 | 58.6 Years STANDARD_DEVIATION 10.7 | 59.9 Years STANDARD_DEVIATION 12.8 | 59.4 Years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 27 Participants | 23 Participants | 12 Participants | 25 Participants | 18 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 7 Participants | 11 Participants | 5 Participants | 12 Participants | 13 Participants | 49 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 20 Participants | 13 Participants | 6 Participants | 13 Participants | 6 Participants | 63 Participants |
| Sex: Female, Male Female | 0 Participants | 7 Participants | 5 Participants | 4 Participants | 9 Participants | 5 Participants | 30 Participants |
| Sex: Female, Male Male | 6 Participants | 20 Participants | 19 Participants | 8 Participants | 16 Participants | 14 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 23 / 27 | 21 / 24 | 7 / 12 | 21 / 25 | 13 / 19 |
| other Total, other adverse events | 6 / 6 | 27 / 27 | 22 / 24 | 12 / 12 | 22 / 25 | 18 / 19 |
| serious Total, serious adverse events | 2 / 6 | 14 / 27 | 16 / 24 | 10 / 12 | 15 / 25 | 12 / 19 |
Outcome results
Primary
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b
The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented.
Time frame: Baseline (Day 1)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b | ECOG 1 | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b | ECOG 0 | 4 Participants |
Primary
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b | 1 Participants |
Primary
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b | Pyrexia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b | Weight decreased | 1 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Prothrombin time prolonged | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Activated partial thromboplastin time prolonged | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Blood alkaline phosphatase increased | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Anaemia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Lymphopenia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Haemoglobin decreased | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Blood bilirubin increased | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Gamma-glutamyltransferase increased | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b | Transaminases increased | 1 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b
A DLT was defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab). The DLTs are: any Grade 4 immune-related adverse event (irAE), any Grade \>=3 non-irAE, \>= Grade 3 colitis, Grade 3 or 4 noninfectious pneumonitis irrespective of duration, Grade 2 pneumonitis, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN. Immune-related AEs are defined as AEs of an immune nature (ie, inflammatory) in the absence of a clear alternative etiology.
Time frame: From first dose of Study drug (Day 1) through 28 days after the administration of MEDI4736 and tremelimumab
Population: Dose limiting toxicity (DLT) evaluable population included all participants in the Phase 1b who received the Study drug and completed safety follow-up through the DLT evaluation period or experience a DLT during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b | 1 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b | TEAEs | 6 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b | TESAEs | 2 Participants |
Primary
Percentage of Participants With Objective Response (OR) in Phase 2
OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response (OR) in Phase 2 | 11.1 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Percentage of Participants With Objective Response (OR) in Phase 2 | 0 Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Percentage of Participants With Objective Response (OR) in Phase 2 | 8.3 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response (OR) in Phase 2 | 4.0 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response (OR) in Phase 2 | 15.8 Percentage of participants |
p-value: 0.237695% CI: [-0.7, 23]Fisher Exact
p-value: 195% CI: [-16.8, 22.4]Fisher Exact
Primary
Progression Free Survival at 6 (PFS-6) Month in Phase 2
The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.
Time frame: From Day 1 upto 6 months
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Progression Free Survival at 6 (PFS-6) Month in Phase 2 | 12.1 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Progression Free Survival at 6 (PFS-6) Month in Phase 2 | NA Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Progression Free Survival at 6 (PFS-6) Month in Phase 2 | 23.3 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival at 6 (PFS-6) Month in Phase 2 | 12.5 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival at 6 (PFS-6) Month in Phase 2 | 5.3 Percentage of participants |
Secondary
Duration of Response (DoR) in Phase 2
The DoR was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression according to RECIST v1.1 that occurred subsequently after response or death due to any cause, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline. Kaplan Meier method was used to evaluate DoR.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with OR were analyzed for the specified outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Duration of Response (DoR) in Phase 2 | NA Months |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Duration of Response (DoR) in Phase 2 | 4.6 Months |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Duration of Response (DoR) in Phase 2 | 7.4 Months |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Duration of Response (DoR) in Phase 2 | 3.1 Months |
Secondary
Duration of Stable Disease (DSD) in Phase 1b
The DSD was defined as the time from the date of first dose of study treatment for Phase 1b until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. DSD was analyzed for participants with SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Duration of Stable Disease (DSD) in Phase 1b | 5.4 Months |
Secondary
Duration of Stable Disease in Phase 2
The DSD was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5 mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. DSD was analyzed for participants with SD.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Duration of Stable Disease in Phase 2 | 3.5 Months |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Duration of Stable Disease in Phase 2 | 3.6 Months |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Duration of Stable Disease in Phase 2 | 7.7 Months |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Duration of Stable Disease in Phase 2 | 4.2 Months |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Duration of Stable Disease in Phase 2 | 3.5 Months |
Secondary
Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2
The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented.
Time frame: Baseline (Day 1)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 1 | 18 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 0 | 9 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 1 | 14 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 0 | 9 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 1 | 8 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 0 | 4 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 1 | 14 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 0 | 11 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 1 | 8 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2 | ECOG 0 | 11 Participants |
Secondary
Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b
Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b | 17.7 mm |
Secondary
Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2
Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with any reduction in tumor size were analyzed for the specified outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | 8.00 mm |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | 21.20 mm |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | -4.00 mm |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | 0.00 mm |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2 | 3.00 mm |
Secondary
Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2
Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Pericardial effusion | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Angina pectoris | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Ventricular tachycardia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Sinus tachycardia | 3 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure congestive | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial tachycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Angina pectoris | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Ventricular tachycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure congestive | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Pericardial effusion | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Tachycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial tachycardia | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Sinus tachycardia | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Pericardial effusion | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Angina pectoris | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Ventricular tachycardia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial tachycardia | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Bradycardia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure congestive | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Pericardial effusion | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Ventricular tachycardia | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial fibrillation | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure congestive | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial tachycardia | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Bradycardia | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Angina pectoris | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure congestive | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial fibrillation | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Tachycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Cardiac failure | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Pericardial effusion | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Ventricular tachycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Atrial tachycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Angina pectoris | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
Secondary
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypoxia | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypotension | 6 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypertension | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Weight decreased | 3 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Sinus tachycardia | 3 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Respiratory distress | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Pyrexia | 5 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypertension | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypotension | 3 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypoxia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Pyrexia | 7 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Respiratory distress | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Sinus tachycardia | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Tachycardia | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Weight decreased | 4 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Weight decreased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Respiratory distress | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypotension | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Bradycardia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypertension | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Pyrexia | 2 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypoxia | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Atrial fibrillation | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Bradycardia | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypoxia | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Pyrexia | 4 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Respiratory distress | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Atrial fibrillation | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Weight decreased | 5 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypertension | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Tachycardia | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypotension | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Pyrexia | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypotension | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypoxia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Tachycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Respiratory distress | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Hypertension | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Weight decreased | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Atrial fibrillation | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Bradycardia | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2 | Sinus tachycardia | 0 Participants |
Secondary
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2
Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood alkaline phosphatase increased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hypothyroidism | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Activated partial thromboplastin time prolonged | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Thyroxine free decreased | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Anaemia | 9 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | White blood cell count decreased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hyperthyroidism | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Platelet count decreased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Alanine aminotransferase increased | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood thyroid stimulating hormone increased | 3 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | International normalised ratio increased | 3 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Gamma-glutamyltransferase increased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood fibrinogen decreased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Aspartate aminotransferase increased | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Tri-iodothyronine free decreased | 2 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Lymphocyte count decreased | 1 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood bilirubin increased | 0 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hepatic function abnormal | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hypothyroidism | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood alkaline phosphatase increased | 2 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Alanine aminotransferase increased | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Lymphocyte count decreased | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Aspartate aminotransferase increased | 2 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Anaemia | 3 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Thyroxine free decreased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood thyroid stimulating hormone increased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | International normalised ratio increased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | White blood cell count decreased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hepatic function abnormal | 1 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Activated partial thromboplastin time prolonged | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hyperthyroidism | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Platelet count decreased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Tri-iodothyronine free decreased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Gamma-glutamyltransferase increased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood fibrinogen decreased | 0 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood bilirubin increased | 2 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Activated partial thromboplastin time prolonged | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | White blood cell count decreased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Anaemia | 3 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Lymphocyte count decreased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | International normalised ratio increased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Platelet count decreased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood fibrinogen decreased | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hepatic function abnormal | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Alanine aminotransferase increased | 2 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Aspartate aminotransferase increased | 3 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood alkaline phosphatase increased | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood bilirubin increased | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Gamma-glutamyltransferase increased | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hyperthyroidism | 1 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hypothyroidism | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood thyroid stimulating hormone increased | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Thyroxine free decreased | 0 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Tri-iodothyronine free decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood alkaline phosphatase increased | 2 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood fibrinogen decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Thyroxine free decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood bilirubin increased | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Platelet count decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Gamma-glutamyltransferase increased | 2 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Activated partial thromboplastin time prolonged | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hyperthyroidism | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | International normalised ratio increased | 1 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Anaemia | 7 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hypothyroidism | 4 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | White blood cell count decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood thyroid stimulating hormone increased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Alanine aminotransferase increased | 2 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Lymphocyte count decreased | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Aspartate aminotransferase increased | 3 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hepatic function abnormal | 0 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Tri-iodothyronine free decreased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Alanine aminotransferase increased | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood fibrinogen decreased | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Aspartate aminotransferase increased | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hypothyroidism | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | White blood cell count decreased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood bilirubin increased | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Platelet count decreased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hepatic function abnormal | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Thyroxine free decreased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Tri-iodothyronine free decreased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Gamma-glutamyltransferase increased | 1 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Activated partial thromboplastin time prolonged | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood alkaline phosphatase increased | 2 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Anaemia | 4 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Blood thyroid stimulating hormone increased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Hyperthyroidism | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | International normalised ratio increased | 0 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2 | Lymphocyte count decreased | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: Day 1 up to 90 days after the last dose (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TESAEs | 14 Participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TEAEs | 27 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TESAEs | 16 Participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TEAEs | 23 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TEAEs | 12 Participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TESAEs | 10 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TESAEs | 15 Participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TEAEs | 22 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TESAEs | 12 Participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2 | TEAEs | 18 Participants |
Secondary
Overall Survival at 12 Months in Phase 2
The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until 12 months. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS and 95% confidence interval.
Time frame: From Day 1 up to 12 months
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Overall Survival at 12 Months in Phase 2 | 37.0 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Overall Survival at 12 Months in Phase 2 | NA Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Overall Survival at 12 Months in Phase 2 | 13.1 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Overall Survival at 12 Months in Phase 2 | 40.7 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Overall Survival at 12 Months in Phase 2 | 29.2 Percentage of participants |
Secondary
Overall Survival (OS) in Phase 2
The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until death due to any cause. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Overall Survival (OS) in Phase 2 | 9.2 Months |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Overall Survival (OS) in Phase 2 | 3.4 Months |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Overall Survival (OS) in Phase 2 | 7.7 Months |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Overall Survival (OS) in Phase 2 | 10.7 Months |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Overall Survival (OS) in Phase 2 | 7.0 Months |
Secondary
Percentage of Participants With Disease Control at 16 Weeks in Phase 1b
The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Time frame: From Day 1 up to 16 weeks
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 1b | 33.3 Percentage of participants |
Secondary
Percentage of Participants With Disease Control at 16 Weeks in Phase 2
The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Time frame: From Day 1 up to 16 weeks
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | 18.5 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | 12.5 Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | 16.7 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | 28.0 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 16 Weeks in Phase 2 | 21.1 Percentage of participants |
Secondary
Percentage of Participants With Disease Control at 24 Weeks in Phase 1b
The disease control rate at 24 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Time frame: From Day 1 up to 24 weeks
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 1b | 16.7 Percentage of participants |
Secondary
Percentage of Participants With Disease Control at 24 Weeks in Phase 2
The disease control rate at 24 weeks was defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.
Time frame: From Day 1 up to 24 weeks
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | 11.1 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | 0 Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | 16.7 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | 12.0 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Disease Control at 24 Weeks in Phase 2 | 15.8 Percentage of participants |
Secondary
Percentage of Participants With Objective Response in Phase 1b
OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization of participants or date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 months post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 1b | 0 Percentage of participants |
Secondary
Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status
Percentage of participants with objective response in Phase 2 by programmed death-ligand (PD-L1) status is reported. PD-L1 is a protein that may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. It plays a role in regulating the immune response against some types of cancers and therefore, is the target for some anticancer drugs. PD-L1 status was based on the percentage of tumor cells from baseline tumor tissue samples with PD-L1 membrane staining: PD-L1 high if \>= 1% tumor cells (better response), PD-L1 low/neg if \< 1% tumor cells (low response).
Time frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 high | 13.3 Percentage of participants |
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 low/negative | 11.1 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 high | 0 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 low/negative | 0 Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 high | 0 Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 low/negative | 25.0 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 low/negative | 0 Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 high | 0 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 high | 33.3 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status | PD-L1 low/negative | 0 Percentage of participants |
Secondary
Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2
Percentage of participants with OR with positive IFN-γ gene expression is reported. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.
Time frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2 | 15.8 Percenatge of Participants |
Secondary
Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2
Percentage of participants with PFS at 6 month with positive IFN-γ gene expression is reported. The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.
Time frame: Day 1 through Day 30 post EOT (approximately 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Only those participants were analyzed who were at risk at 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2 | 5.3 Percentage of Participants |
Secondary
Progression Free Survival at 6 Month in Phase 1b
The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Phase 1b participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Time frame: From Day 1 upto 6 months
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Progression Free Survival at 6 Month in Phase 1b | 16.7 Percentage of participants |
Secondary
Progression Free Survival at 9 Month (PFS-9) in Phase 2
The PFS-9 is the 9-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 9 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, C participants or the date of first dose of study drug for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Time frame: From Day 1 up to 9 months
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Progression Free Survival at 9 Month (PFS-9) in Phase 2 | 12.1 Percentage of participants |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Progression Free Survival at 9 Month (PFS-9) in Phase 2 | NA Percentage of participants |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Progression Free Survival at 9 Month (PFS-9) in Phase 2 | NA Percentage of participants |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival at 9 Month (PFS-9) in Phase 2 | 4.2 Percentage of participants |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival at 9 Month (PFS-9) in Phase 2 | 5.3 Percentage of participants |
Secondary
Progression Free Survival in Phase 2
The PFS was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study treatment for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Progression Free Survival in Phase 2 | 1.8 Months |
| Phase 2 Arm B-M10 mg/kg (Q2W) | Progression Free Survival in Phase 2 | 1.6 Months |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Progression Free Survival in Phase 2 | 1.7 Months |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival in Phase 2 | 1.8 Months |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Progression Free Survival in Phase 2 | 1.8 Months |
Secondary
Time to Response (TTR) in Phase 2
TTR: time from date of randomization of participants for Arm A, B, and C or date of first dose of study drug for Arm D and Arm E until first documented OR per RECIST v1.1. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization/date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in SOD of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD; PD: at least 20% increase in SOD of target lesions from smallest sum (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method used to evaluate TTR.
Time frame: From Day 1 up to End of the Treatment (EOT), 90 days post-EOT, every 3 months (Q3M) after Day 90 post-EOT up to 12 month post-EOT, and every 6 months after month 12 post-EOT (approximately up to 4 years and one month)
Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with OR were analyzed for the specified outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W) | Time to Response (TTR) in Phase 2 | 1.9 Months |
| Phase 2 Arm C-T10 mg/kg (Q4W) | Time to Response (TTR) in Phase 2 | 2.7 Months |
| Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Time to Response (TTR) in Phase 2 | 7.2 Months |
| Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W) | Time to Response (TTR) in Phase 2 | 1.8 Months |