Back to resultsAnti-PD-1 in Combination With Chemotherapy as First-Line Treatment to Lung Cancer
Primary Purpose
Locally Advanced Lung Cancer; Metastatic Lung Cancer
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Paclitaxel
Gemcitabine
Etoposide
Pemetrexed
Cisplatin
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Lung Cancer; Metastatic Lung Cancer
Eligibility Criteria
Key Inclusion Criteria:
- Male or female, aged 18-75 years on the day of signing informed consent.
Have histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC, squamous NSCLC, or extensive-stage SCLC.
Note: Participants with mixed adenosquamous carcinoma may also be enrolled on a case-by-case basis after discussion with the medical monitors.
- Have had no prior systemic therapy for advanced or metastatic disease. Prior neoadjuvant/adjuvant therapy or chemoradiation therapy with curative intent should have been completed at least 6 months prior to documentation of recurrence of disease.
- Participants must be able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or at least 10 unstained FFPE slides) with an associated pathological report.
Key Exclusion Criteria:
- Participants with a sensitizing mutation in EGFR gene or an ALK fusion oncogene (specifically for participants with non- squamous NSCLC). Participants with unknown mutation/fusion status of EGFR and/or ALK must take the respective test at the investigational sites (or other designated sites) prior to enrolment.
- Prior malignancy active within the previous 2 years exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
- Prior therapies targeting PD-1, PD-L1 or PD-L2
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Chinese Academy of Medical Sciences Tumor Hospital
- Beijing Cancer Hospital
- Beijing Chest Hospital
- Henan Cancer Hospital
- Jaingsu People's Hospital
- Jilin University First Hospital
- Jilin Cancer Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Non-squamous NSCLC
Squamous NSCLC Cohort A
Squamous NSCLC Cohort B
SCLC
Arm Description
Day 1 of each 21-day (3 weeks) cycle: Tislelizumab + pemetrexed + cisplatin 75 mg/m²/day IV (or carboplatin AUC 5). Pemetrexed plus cisplatin (or carboplatin) should be given for up to 4 cycles. Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate. Pemetrexed maintenance after completion of doublet chemotherapy is permitted.
Tislelizumab every 3 weeks (Q3W) + paclitaxel + cisplatin (or carboplatin), Q3W. Paclitaxel plus cisplatin (or carboplatin) will be administered for 4-6 cycles. Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Tislelizumab Q3W on Day 1 + gemcitabine on Day 1 and Day 8 + cisplatin IV (or carboplatin) on Day 1. Gemcitabine plus cisplatin (or carboplatin) will be administered for 4-6 cycles. Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Tislelizumab Q3W on Day 1, etoposide on Days 1, 2, and 3 + cisplatin (or carboplatin) on Day 1. Etoposide and cisplatin (or carboplatin) will be administered for 4-6 cycles. Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Outcomes
Primary Outcome Measures
The objective response rate (ORR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Secondary Outcome Measures
The incidence and severity of adverse events (AEs) according to NCI-CTCAE Version 4.03
Duration of Response (DoR) - defined as the time from the first determination of a confirmed objective response according to RECIST v1.1 until the first documentation of progression or death, whichever comes first
Progression-Free Survival (PFS) - defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression using RECIST v1.1 or death, whichever occurs first
Disease Control Rate (DCR) - defined as the proportion of participants who achieve CR, PR and SD using RECIST v1.1
Pharmacokinetic evaluations of BGB-A317 in combination with chemotherapy: including but not limited to Ctrough
Anti-BGB-A317 antibody: immunogenic responses to BGB-A317 will be assessed to determine occurrence of anti-drug antibody.
The abnormality of laboratory tests according to NCI CTCAE Version 4.03
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03432598
Brief Title
Anti-PD-1 in Combination With Chemotherapy as First-Line Treatment to Lung Cancer
Official Title
A Phase II, Open-Label, Multi-Cohort Study to Investigate the Preliminary Antitumor Activity, Safety, and Pharmacokinetics of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With Chemotherapy as First-Line Treatment in Chinese Subjects With Locally Advanced or Metastatic Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
August 24, 2017 (Actual)
Primary Completion Date
February 25, 2019 (Actual)
Study Completion Date
December 21, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a Phase II, open-label, 4-cohort study of the monoclonal antibody BGB-A317 in combination with standard platinum-based chemotherapy in participants with advanced NSCLC or SCLC. The 4 cohorts will be enrolled concurrently including non-squamous NSCLC Cohort, squamous NSCLC Cohort A, squamous NSCLC Cohort B and SCLC Cohort. Participants with a mixed adenocarcinoma and squamous cell NSCLC will be allocated to one of the NSCLC cohorts based on the predominant histopathological profile. (e.g., participants with adenocarcinoma component accounting for > 50% will be allocated to non-squamous NSCLC cohort.). Participants with squamous NSCLC will be sequentially enrolled into either of the 2 squamous NSCLC cohorts by the trial stage i.e. the sequence of the enrollment for the squamous NSCLC cohorts will be as Cohort A safety run-in Stage, followed by Cohort B safety run-in Stage, Cohort A dose-expansion stage and Cohort B dose-expansion Stage.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Lung Cancer; Metastatic Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Non-squamous NSCLC
Arm Type
Experimental
Arm Description
Day 1 of each 21-day (3 weeks) cycle: Tislelizumab + pemetrexed + cisplatin 75 mg/m²/day IV (or carboplatin AUC 5).
Pemetrexed plus cisplatin (or carboplatin) should be given for up to 4 cycles.
Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate. Pemetrexed maintenance after completion of doublet chemotherapy is permitted.
Arm Title
Squamous NSCLC Cohort A
Arm Type
Experimental
Arm Description
Tislelizumab every 3 weeks (Q3W) + paclitaxel + cisplatin (or carboplatin), Q3W.
Paclitaxel plus cisplatin (or carboplatin) will be administered for 4-6 cycles.
Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Arm Title
Squamous NSCLC Cohort B
Arm Type
Experimental
Arm Description
Tislelizumab Q3W on Day 1 + gemcitabine on Day 1 and Day 8 + cisplatin IV (or carboplatin) on Day 1.
Gemcitabine plus cisplatin (or carboplatin) will be administered for 4-6 cycles.
Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Arm Title
SCLC
Arm Type
Experimental
Arm Description
Tislelizumab Q3W on Day 1, etoposide on Days 1, 2, and 3 + cisplatin (or carboplatin) on Day 1.
Etoposide and cisplatin (or carboplatin) will be administered for 4-6 cycles.
Following either completion of or discontinuation from chemotherapy, tislelizumab will be continued as scheduled, if clinically appropriate.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
BGB-A317
Intervention Description
Administered 200 mg intravenously (IV) as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Administered 175 mg/m² IV as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Administered 1250 mg/m² IV as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
Administered 100 mg/m2 IV as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
Administered 500 mg/m² IV as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Administered 75 mg/m²/day IV as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Administered AUC 5 as specified in the treatment arm
Primary Outcome Measure Information:
Title
The objective response rate (ORR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
The incidence and severity of adverse events (AEs) according to NCI-CTCAE Version 4.03
Time Frame
Up to 4 years
Title
Duration of Response (DoR) - defined as the time from the first determination of a confirmed objective response according to RECIST v1.1 until the first documentation of progression or death, whichever comes first
Time Frame
Up to 4 years
Title
Progression-Free Survival (PFS) - defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression using RECIST v1.1 or death, whichever occurs first
Time Frame
Up to 4 years
Title
Disease Control Rate (DCR) - defined as the proportion of participants who achieve CR, PR and SD using RECIST v1.1
Time Frame
Up to 4 years
Title
Pharmacokinetic evaluations of BGB-A317 in combination with chemotherapy: including but not limited to Ctrough
Time Frame
Up to 4 years
Title
Anti-BGB-A317 antibody: immunogenic responses to BGB-A317 will be assessed to determine occurrence of anti-drug antibody.
Time Frame
Up to 4 years
Title
The abnormality of laboratory tests according to NCI CTCAE Version 4.03
Time Frame
Up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female, aged 18-75 years on the day of signing informed consent.
Have histologically or cytologically confirmed locally advanced or metastatic non-squamous NSCLC, squamous NSCLC, or extensive-stage SCLC.
Note: Participants with mixed adenosquamous carcinoma may also be enrolled on a case-by-case basis after discussion with the medical monitors.
Have had no prior systemic therapy for advanced or metastatic disease. Prior neoadjuvant/adjuvant therapy or chemoradiation therapy with curative intent should have been completed at least 6 months prior to documentation of recurrence of disease.
Participants must be able to provide fresh or archival tumor tissues (formalin-fixed paraffin-embedded [FFPE] blocks or at least 10 unstained FFPE slides) with an associated pathological report.
Key Exclusion Criteria:
Participants with a sensitizing mutation in EGFR gene or an ALK fusion oncogene (specifically for participants with non- squamous NSCLC). Participants with unknown mutation/fusion status of EGFR and/or ALK must take the respective test at the investigational sites (or other designated sites) prior to enrolment.
Prior malignancy active within the previous 2 years exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
Prior therapies targeting PD-1, PD-L1 or PD-L2
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Wang, MD
Organizational Affiliation
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chinese Academy of Medical Sciences Tumor Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
Beijing Chest Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
133500
Country
China
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Facility Name
Jaingsu People's Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Jilin University First Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
132000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
32769013
Citation
Wang Z, Zhao J, Ma Z, Cui J, Shu Y, Liu Z, Cheng Y, Leaw SJ, Wu Y, Ma Y, Tan W, Ma X, Zhang Y, Wang J. A Phase 2 Study of Tislelizumab in Combination With Platinum-Based Chemotherapy as First-line Treatment for Advanced Lung Cancer in Chinese Patients. Lung Cancer. 2020 Sep;147:259-268. doi: 10.1016/j.lungcan.2020.06.007. Epub 2020 Jun 20. Erratum In: Lung Cancer. 2021 Aug;158:166-167.
Results Reference
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Anti-PD-1 in Combination With Chemotherapy as First-Line Treatment to Lung Cancer
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