Extensive Stage Small Cell Lung Cancer
Conditions
Keywords
Extensive Stage, Small Cell Lung Cancer, Anti-PD-1 Monoclonal Antibody
Brief summary
This is a randomized, double-blind, multicenter, phase III clinical study to compare the clinical efficacy and safety of HLX10+ Chemotherapy vs placebo+Chemotherapy in Previously Untreated Patients with Extensive Stage Small Cell Lung Cancer. Eligible subjects in this study will be randomized to Arm A or Arm B at 2:1 ratio as follows: Arm A (HLX10 arm): HLX10 + chemotherapy (Carboplatin-Etoposide) ; Arm B (placebo arm): Placebo + chemotherapy (Carboplatin-Etoposide); The three stratification factors for randomization include: PD-L1 expression level (negative, positive, not available), Brain metastasis (yes versus no), Age (≥ 65 years versus \< 65 years)
Detailed description
After screening, subjects meeting the inclusion criteria and none of the exclusion criteria will be enrolled. Included subjects will be treated with HLX10 or placebo in combination with chemotherapy once every 3 weeks, until disease progression, death, intolerable toxicity, withdrawal of informed consent, or occurrence of other reasons specified in the protocol (whichever occurs first).
Interventions
DRUGHLX10
HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.
chemotherapeutics
DRUGplacebo
placebo
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans Administration Lung Study Group staging system). * No prior systemic therapy for ES-SCLC * Major organs are functioning well * Participant must keep contraception
Exclusion criteria
* Histologically or cytologically confirmed mixed SCLC. * Known history of severe allergy to any monoclonal antibody. * Known hypersensitivity to carboplatin or etoposide. * Pregnant or breastfeeding females. * Patients with a known history of psychotropic drug abuse or drug addiction. * Patients who have other factors that could lead to the early termination of this study based on the investigator's judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| OS | The period from randomization through death regardless of causality (up to approximately 56 months) | Overall survival (OS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Assessed by IRRC According to RECIST 1.1 | From randomization initiation to the first documentation of PD or death regardless of causality, whichever occurs first (up to approximately 56 months). | PFS is defined as a period from randomization initiation to the first documentation of PD or death regardless of causality (whichever occurs first). |
| Objective Response Rate | From baseline until PR or CR, whichever occurs first (up to approximately 56 months) | The ORR is defined as the proportion of subjects with a best overall response of CR or PR, according to RECIST 1.1. The best overall response will be defined as the best response across all time points in the order of CR, PR, SD, PD, and not NE. |
| Duration of Response | From the first documentation of response (CR or PR) through the first documentation of PD or death, whichever occurs first (up to approximately 56 months). | DOR is defined as a period from the first documentation of response (CR or PR) through the first documentation of PD or death (whichever occurs first). |
Countries
Georgia, Poland, Russia, Turkey (Türkiye), Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A HLX 10+chemotherapy (Carboplatin-Etoposide)
HLX10: HLX10 is an innovative monoclonal antibody targeting PD-1，developed by Shanghai Henlius Biotech, Inc.
carboplatin and etoposide: chemotherapeutics | 389 |
| Group B Placebo+chemotherapy (Carboplatin-Etoposide)
carboplatin and etoposide: chemotherapeutics
placebo: placebo | 196 |
| Total | 585 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 281 | 166 |
| Overall Study | Lost to Follow-up | 12 | 8 |
| Overall Study | Withdrawal by Subject | 19 | 10 |
Baseline characteristics
| Characteristic | Group B | Total | Group A |
|---|---|---|---|
| Age, Continuous | 62 years | 62 years | 63 years |
| Race/Ethnicity, Customized Asian | 139 Participants | 401 Participants | 262 Participants |
| Race/Ethnicity, Customized Non-Asian | 57 Participants | 184 Participants | 127 Participants |
| Sex: Female, Male Female | 164 Participants | 236 Participants | 72 Participants |
| Sex: Female, Male Male | 32 Participants | 349 Participants | 317 Participants |
| Smoking history Current smoker | 48 Participants | 150 Participants | 102 Participants |
| Smoking history Former smoker | 113 Participants | 319 Participants | 206 Participants |
| Smoking history Never smoker | 35 Participants | 116 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 224 / 389 | 140 / 196 |
| other Total, other adverse events | 367 / 389 | 187 / 196 |
| serious Total, serious adverse events | 146 / 389 | 71 / 196 |
Outcome results
Primary
OS
Overall survival (OS)
Time frame: The period from randomization through death regardless of causality (up to approximately 56 months)
Population: Analyses of the primary efficacy endpoint is based on the ITT. The ITT Population comprises all participants to whom study intervention has been randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A Groups | OS | 15.77 month |
| B Groups | OS | 11.10 month |
Comparison: Defined as a period from randomization through death regardless of causality. Data of patients without a death record will be censored on the last known survival date. COX proportional risk model will be used to estimate HR and its 95% confidence interval (CI); the Kaplan-Meier method will be used to estimate the median, and the Kaplan-Meier curve will be plotted.p-value: <0.00195% CI: [0.496, 0.763]Log Rank
Secondary
Duration of Response
DOR is defined as a period from the first documentation of response (CR or PR) through the first documentation of PD or death (whichever occurs first).
Time frame: From the first documentation of response (CR or PR) through the first documentation of PD or death, whichever occurs first (up to approximately 56 months).
Population: DOR is analyzed based on ITT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A Groups | Duration of Response | 6.80 month |
| B Groups | Duration of Response | 4.17 month |
Secondary
Objective Response Rate
The ORR is defined as the proportion of subjects with a best overall response of CR or PR, according to RECIST 1.1. The best overall response will be defined as the best response across all time points in the order of CR, PR, SD, PD, and not NE.
Time frame: From baseline until PR or CR, whichever occurs first (up to approximately 56 months)
Population: ORR is analyzed based on ITT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A Groups | Objective Response Rate | 268 Participants |
| B Groups | Objective Response Rate | 115 Participants |
Secondary
Progression Free Survival (PFS) Assessed by IRRC According to RECIST 1.1
PFS is defined as a period from randomization initiation to the first documentation of PD or death regardless of causality (whichever occurs first).
Time frame: From randomization initiation to the first documentation of PD or death regardless of causality, whichever occurs first (up to approximately 56 months).
Population: Analysis of PFS is based on ITT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A Groups | Progression Free Survival (PFS) Assessed by IRRC According to RECIST 1.1 | 5.82 month |
| B Groups | Progression Free Survival (PFS) Assessed by IRRC According to RECIST 1.1 | 4.34 month |
p-value: 0.00195% CI: [0.381, 0.576]Log Rank