Small-cell Lung Cancer
Conditions
Brief summary
This is a multi-center, open-label, phase II study of intravenous (IV) SHR-1210 at 200mg,q2w in combination with Apatinib at one dose (375mg). Comparison of 3 different dose schedules in subjects with extensive-stage disease small cell lung cancer. SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1). Apatinib is a new kind of selective Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) tyrosine kinase inhibitor (TKI). The study is composed of two parts. Part 1 of the study will determine the safety and tolerability of SHR-1210 in combination with Apatinib in first 6 subjects of each arm. The second phase of treatment was carried out by selecting one group of administration mode and the tolerated dose of Apatinib. Part 2 of the study will determine the safety and efficacy of SHR-1210 in combination with Apatinib in 39 subjects.
Interventions
DRUGSHR-1210
A humanized anti-PD-1 monoclonal antibody
DRUGApatinib
A tyrosine kinase inhibitor selectively targeting VEGFR-2
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Signed inform consent form. 2. Age \>= 18 years and \<= 70 years. 3. Histologically or cytologically confirmed small cell lung cancer. 4. ED-SCLC according to Veterans Administration Lung Study Group. 5. Radiographically progression following a platinum-based standard prior chemotherapy regimen. 6. Eastern Cooperative Oncology Group performance status of 0 or 1. 7. Measurable disease as defined by RECIST v1.1. 8. Life expectancy \>= 8 weeks. 9. Adequate hematologic and end organ function.
Exclusion criteria
1. Histologically or cytologically confirmed mixed non-small cell and small cell carcinoma. 2. Prior exposure to therapeutic anticancer vaccines; prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies. 3. Prior exposure to anti-VEGF or anti-VEGFR therapy. 4. Active brain metastasis or meningeal metastasis. 5. Clinically significant third space effusion (e.g., uncontrolled pericardial effusion, ascites or pleural effusion by extraction or other treatment). 6. Known hypersensitivity to study drug or any of its excipients; known hypersensitivity to any antibody. 7. Treatment with any other investigational agent or participation in another clinical trial within 4 weeks prior to screening. 8. Other conditions that the investigator thinks unsuitable in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 24 months | Evaluation of adverse event rate according to CTCAE v4.03 |
| ORR | 6 months | Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented. | Progression-free survival according to RECIST v1.1 |
| DoR | Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented. | Duration of response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Duration of response (DoR): DoR will only be performed in subjects who have a confirmed tumor response (CR or PR) after treatment |
| TTR | Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented. | Time to response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Time to response (TTR): date of first dose to date of first documented CR or PR) |
| OS | on average of 2 years | Overall survival |
| DCR | Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented. | Disease control rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Disease control rate (DCR): CR+PR+SD |
| OS Rate | 6 months | Overall survival rate |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A(SHR-1210+Apatinib) SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD | 47 |
| B(SHR-1210+Apatinib) SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (5 Days on, 2 Days off) | 6 |
| C(SHR-1210+Apatinib) SHR-1210 200mg, IV, Q2W and Apatinib 375mg, PO, QD (7 Days on, 7 Days off) | 6 |
| Total | 59 |
Baseline characteristics
| Characteristic | A(SHR-1210+Apatinib) | Total | C(SHR-1210+Apatinib) | B(SHR-1210+Apatinib) |
|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 6.36 | 59.6 years STANDARD_DEVIATION 7.08 | 54.2 years STANDARD_DEVIATION 10.68 | 59.3 years STANDARD_DEVIATION 7.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 47 Participants | 59 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 47 participants | 59 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 51 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 17 / 47 | 1 / 6 | 2 / 6 |
| other Total, other adverse events | 47 / 47 | 6 / 6 | 5 / 6 |
| serious Total, serious adverse events | 27 / 47 | 4 / 6 | 2 / 6 |
Outcome results
Primary
Adverse Event
Evaluation of adverse event rate according to CTCAE v4.03
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A(SHR-1210+Apatinib) | Adverse Event | 47 participants |
| B(SHR-1210+Apatinib) | Adverse Event | 6 participants |
| C(SHR-1210+Apatinib) | Adverse Event | 5 participants |
Primary
ORR
Objective response rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Over all response：CR+PR)
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A(SHR-1210+Apatinib) | ORR | 34.0 percentage of number of people in FAS |
| B(SHR-1210+Apatinib) | ORR | 33.3 percentage of number of people in FAS |
| C(SHR-1210+Apatinib) | ORR | 33.3 percentage of number of people in FAS |
Secondary
DCR
Disease control rate according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1; Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to\<10 mm; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Disease control rate (DCR): CR+PR+SD
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A(SHR-1210+Apatinib) | DCR | 68.1 percentage of number of people in FAS |
| B(SHR-1210+Apatinib) | DCR | 100.0 percentage of number of people in FAS |
| C(SHR-1210+Apatinib) | DCR | 50.0 percentage of number of people in FAS |
Secondary
DoR
Duration of response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Duration of response (DoR): DoR will only be performed in subjects who have a confirmed tumor response (CR or PR) after treatment
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A(SHR-1210+Apatinib) | DoR | 6.2 months |
| B(SHR-1210+Apatinib) | DoR | 4.2 months |
| C(SHR-1210+Apatinib) | DoR | 8.0 months |
Secondary
OS
Overall survival
Time frame: on average of 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A(SHR-1210+Apatinib) | OS | 8.8 months |
| B(SHR-1210+Apatinib) | OS | 11.2 months |
| C(SHR-1210+Apatinib) | OS | 5.4 months |
Secondary
OS Rate
Overall survival rate
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A(SHR-1210+Apatinib) | OS Rate | 63.8 percentage of number of people in FAS |
| B(SHR-1210+Apatinib) | OS Rate | 66.7 percentage of number of people in FAS |
| C(SHR-1210+Apatinib) | OS Rate | 44.4 percentage of number of people in FAS |
Secondary
PFS
Progression-free survival according to RECIST v1.1
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A(SHR-1210+Apatinib) | PFS | 3.6 months |
| B(SHR-1210+Apatinib) | PFS | 3.6 months |
| C(SHR-1210+Apatinib) | PFS | 1.2 months |
Secondary
TTR
Time to response according to RECIST v1.1 (Response was assessed with CT or MRI using RECIST v1.1, Time to response (TTR): date of first dose to date of first documented CR or PR)
Time frame: Imaging assessment was performed on C1D28 and every 8 weeks after C1D28 until radiographic progressive disease (PD) was documented.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A(SHR-1210+Apatinib) | TTR | 1.0 months |
| B(SHR-1210+Apatinib) | TTR | 1.8 months |
| C(SHR-1210+Apatinib) | TTR | 4.6 months |