Advanced or Metastatic Esophageal Squamous Cell Cancer Without Previous Systemic Chemotherapy
Conditions
Brief summary
This is one randomized, double-blind, multi-center, placebo-controlled phase III study. The objective of this study is to compare the effectiveness and safety of JS001 combined with paclitaxel and cisplatin(TP regimen )with placebo combined with TP regimen in patients with advanced or metastatic Esophageal Squamous Cell Carcinoma(ESCC )who have not received systemic chemotherapy previously.
Interventions
BIOLOGICALToripalimab
TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy or placebo combine with chemotherapy
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
： Inclusion criteria for oesophageal cancer Histologically or cytologically diagnosed locally advanced / recurrent or metastatic ESCC without radical treatment; No prior systemic anti-tumor therapy for recurrent or metastatic tumor. No recurrence at least 6 months from the end of last treatment in the patients previously receiving adjuvant, neoadjuvant chemotherapy/radiotherapy/chemoradiotherapy and radical therapy for non-metastatic disease (No recurrence at least 12 months from the end of last treatment in the patients previously receiving adjuvant chemotherapy/chemoradiotherapy with TP regimen); No risk of major hemorrhage or esophageal fistula, for example, large ulcer at the lesion is considered as the risk for major hemorrhage and esophageal fistula, the patient is not suitable to be enrolled. Subjects with tumor directly invading adjacent organs such as the aorta or trachea (T4b disease) should be closely assessed for risk of hemorrhage or fistula and consult the sponsor prior to enrollment. General requirements for inclusion: Signed informed consent; Male or female aged 18 to 70 years ECOG score 0 or 1; Expected survival longer than 3 months; Agreement upon providing previously reserved tumor tissue specimen or biopsied tumor lesion tissue for biomarker analysis. At least one measurable lesion in accordance with RECIST 1.1 (only when clear progression of disease occurs after radiotherapy for the previously irradiated lesion, the lesion can be used as measurable lesion). Good organ function level: Hematology: neutrophil ≥1.5×10\^9/L, hemoglobin ≥9 g/dL and platelet ≥100×10\^9/L. Hepatic function: bilirubin ≤1.5 time of upper limit of normal (ULN) (patients who are known to have Gilbert disease and serum bilirubin level ≤3 times of ULN can be enrolled), AST and ALT ≤2.5 times of ULN (in case of hepatic metastasis, AST /ALT≤5 times of ULN), and alkaline phosphatase≤3 times of ULN (in case of hepatic or bone metastasis, ALP≤5 times of ULN); albumin ≥3g / dL; International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN. Renal function: serum creatinine ≤1.5 × ULN or estimated glomerular filtration rate in accordance with Cockcroft-Gault formula: creatinine clearance ≥60 mL/min ((140 - age)x(weight，kg)x(0.85，for women))/(72 x(serum creatinine，mg/dL)) Or: ((140 - age)x(weight，kg)x(0.85，for women))/(0.818 x(serum creatinine，μmol/L)) Women who meet the following criteria are eligible to be included and participate in the study: No childbearing potential (e.g., physiologically infertile), women meeting any one of the following conditions: Having undergone uterectomy, Having undergone bilateral oophorectomy (oophorectomy), Having undergone ligation of bilateral fallopian tubes, or Postmenopause (total duration of menopause ≥1 year). Having childbearing potential, serum pregnancy test negative at screening (within 7 days prior to the first dose of study drug), and adequate contraceptive measures taken prior to entry in the study and throughout the study, until 60 days after the last dose of the study drug. The adequate contraceptive measure taken continuously in accordance with the instruction on the contraceptive product and physician's guidance is defined as below: Any intrauterine device confirmed to have a failure rate for contraception less than 1% per year Dual barrier contraception is defined as the condom with spermicidal gel, foam, suppository or film; or diaphragma with spermicide; or male condom and diaphragma.
Exclusion criteria
Cancer-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS((Progression-Free Surviv) | PFS: up to 2years | To evaluate the differences in PFS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review \[BICR\] per RECIST 1.1 criteria). |
| OS (Overall Survival) | up to 2 years | To evaluate the differences in OS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review \[BICR\] per RECIST 1.1 criteria) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR(Duration of Response: Recist 1.1,BICR ) | Up to 2 approximately years | To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed duration of response (DoR) according to RECIST v1.1 DOR is defined as the time from first documented response to first documented evidence of disease progression or to death, whichever comes first. |
| TTR(Time to Initial Response:BICR ) | Up to 2 approximately years | To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed Time to initial Response (TTR) according to RECIST v1.1 TTR is defined as the time from randomization to the first recorded response (CR or PR). |
| PFS | Up to 2 approximately years | To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy，as measured by investigator-assessed progression free survival (PFS) according to RECIST v1.1 |
| PFS Rate:BICR | Up to 1 years | 1 years PFS rate |
| OS Rate | up to 2 years | 2 years OS rate |
| PFS Assessed Per irRECIST | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST |
| ORR(Overall Response Rate:BICR) | Up to 2 approximately years | To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed overall response rate (ORR), daccording to RECIST v1.1; ORR:Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| DoR Assessed Per irRECIST:BICR | From date of response until progressive disease. Up to 2 approximately years | To evaluate DOR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST |
| DCR Assessed Per irRECIST | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST |
| TTR Assessed Per irRECIST:BICR | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate TTR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST |
| Patient-Reported Outcomes Collected Via the EORTC QLQ-C30 | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population. |
| Patient-Reported Outcomes Collected Via the EORTC QLQ-OES18 | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population. |
| ORR Assessed Per irRECIST | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years | To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST |
| DCR(Disease Control Rate:BICR ) | Up to 2 approximately years | To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed disease control rate (DCR) according to RECIST v1.1 DCR is defined as the proportion of patients with the best efficacy of CR or PR or SD. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Toripalimab Toripalimab combine with paclitaxel and cisplatin
Toripalimab: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy or placebo combine with chemotherapy | 257 |
| Placebo Placebo combine with paclitaxel and cisplatin
Toripalimab: TORIPALIMAB INJECTION(JS001 ) combine with chemotherapy or placebo combine with chemotherapy | 257 |
| Total | 514 |
Baseline characteristics
| Characteristic | Toripalimab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 101 Participants | 94 Participants | 195 Participants |
| Age, Categorical Between 18 and 65 years | 156 Participants | 163 Participants | 319 Participants |
| Age, Continuous | 61.30 years STANDARD_DEVIATION 8.04 | 60.90 years STANDARD_DEVIATION 7.3 | 61.1 years STANDARD_DEVIATION 7.67 |
| Race/Ethnicity, Customized Asian | 257 Participants | 257 Participants | 514 Participants |
| Region of Enrollment China | 257 participants | 257 participants | 514 participants |
| Sex: Female, Male Female | 40 Participants | 37 Participants | 77 Participants |
| Sex: Female, Male Male | 217 Participants | 220 Participants | 437 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 174 / 257 | 198 / 257 |
| other Total, other adverse events | 255 / 257 | 255 / 257 |
| serious Total, serious adverse events | 93 / 257 | 74 / 257 |
Outcome results
Primary
OS (Overall Survival)
To evaluate the differences in OS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review \[BICR\] per RECIST 1.1 criteria)
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | OS (Overall Survival) | 17.7 months |
| Placebo | OS (Overall Survival) | 12.9 months |
Primary
PFS((Progression-Free Surviv)
To evaluate the differences in PFS following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized patient population with advanced or metastatic ESCC who had not previously received systemic chemotherapy (as assessed by blinded independent central review \[BICR\] per RECIST 1.1 criteria).
Time frame: PFS: up to 2years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | PFS((Progression-Free Surviv) | 5.7 months |
| Placebo | PFS((Progression-Free Surviv) | 5.5 months |
Secondary
DCR Assessed Per irRECIST
To evaluate DCR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | DCR Assessed Per irRECIST | 232 Participants |
| Placebo | DCR Assessed Per irRECIST | 218 Participants |
Secondary
DCR(Disease Control Rate:BICR )
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed disease control rate (DCR) according to RECIST v1.1 DCR is defined as the proportion of patients with the best efficacy of CR or PR or SD.
Time frame: Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | DCR(Disease Control Rate:BICR ) | 229 Participants |
| Placebo | DCR(Disease Control Rate:BICR ) | 211 Participants |
Secondary
DoR Assessed Per irRECIST:BICR
To evaluate DOR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
Time frame: From date of response until progressive disease. Up to 2 approximately years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | DoR Assessed Per irRECIST:BICR | 5.6 months |
| Placebo | DoR Assessed Per irRECIST:BICR | 4.2 months |
Secondary
DOR(Duration of Response: Recist 1.1,BICR )
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed duration of response (DoR) according to RECIST v1.1 DOR is defined as the time from first documented response to first documented evidence of disease progression or to death, whichever comes first.
Time frame: Up to 2 approximately years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | DOR(Duration of Response: Recist 1.1,BICR ) | 5.6 months |
| Placebo | DOR(Duration of Response: Recist 1.1,BICR ) | 4.2 months |
Secondary
ORR Assessed Per irRECIST
To evaluate ORR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | ORR Assessed Per irRECIST | 180 Participants |
| Placebo | ORR Assessed Per irRECIST | 136 Participants |
Secondary
ORR(Overall Response Rate:BICR)
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed overall response rate (ORR), daccording to RECIST v1.1; ORR:Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | ORR(Overall Response Rate:BICR) | 178 Participants |
| Placebo | ORR(Overall Response Rate:BICR) | 134 Participants |
Secondary
OS Rate
2 years OS rate
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Toripalimab | OS Rate | 39.1 Percentage of Participants |
| Placebo | OS Rate | 27.1 Percentage of Participants |
Secondary
Patient-Reported Outcomes Collected Via the EORTC QLQ-C30
To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
Secondary
Patient-Reported Outcomes Collected Via the EORTC QLQ-OES18
To evaluate the quality of life (QoL) following JS001 in combination with TP regimen compared to placebo in combination with TP regimen in all randomized population.
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
Secondary
PFS
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy，as measured by investigator-assessed progression free survival (PFS) according to RECIST v1.1
Time frame: Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | PFS | 128 Participants |
| Placebo | PFS | 167 Participants |
Secondary
PFS Assessed Per irRECIST
To evaluate PFS of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Toripalimab | PFS Assessed Per irRECIST | 128 Participants |
| Placebo | PFS Assessed Per irRECIST | 160 Participants |
Secondary
PFS Rate:BICR
1 years PFS rate
Time frame: Up to 1 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Toripalimab | PFS Rate:BICR | 27.8 Percentage of Participants |
| Placebo | PFS Rate:BICR | 6.1 Percentage of Participants |
Secondary
TTR Assessed Per irRECIST:BICR
To evaluate TTR of JS001 plus chemotherapy compared with placebo plus chemotherapy according to irRECIST
Time frame: From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 2 approximately years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | TTR Assessed Per irRECIST:BICR | 1.4 months |
| Placebo | TTR Assessed Per irRECIST:BICR | 1.4 months |
Secondary
TTR(Time to Initial Response:BICR )
To evaluate the efficacy of JS001 plus chemotherapy compared with placebo plus chemotherapy, as measured by blind independent review committee BIRC and investigator-assessed Time to initial Response (TTR) according to RECIST v1.1 TTR is defined as the time from randomization to the first recorded response (CR or PR).
Time frame: Up to 2 approximately years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Toripalimab | TTR(Time to Initial Response:BICR ) | 1.4 months |
| Placebo | TTR(Time to Initial Response:BICR ) | 1.4 months |