Anti-PD-1 in Combination With Chemotherapy as First-Line Treatment to Lung Cancer

Study Overview
=================
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.

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

Conditions
-----------------
Locally Advanced Lung Cancer; Metastatic Lung Cancer

Intervention / Treatment
-----------------
* Drug: Tislelizumab
* Drug: Paclitaxel
* Drug: Gemcitabine
* Drug: Etoposide
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-squamous NSCLC<br>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. | Drug: Tislelizumab<br>* Administered 200 mg intravenously (IV) as specified in the treatment arm<br>* Other names: BGB-A317;Drug: Pemetrexed<br>* Administered 500 mg/m² IV as specified in the treatment arm<br>Drug: Cisplatin<br>* Administered 75 mg/m²/day IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Administered AUC 5 as specified in the treatment arm<br>|
| Experimental: Squamous NSCLC Cohort A<br>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. | Drug: Tislelizumab<br>* Administered 200 mg intravenously (IV) as specified in the treatment arm<br>* Other names: BGB-A317;Drug: Paclitaxel<br>* Administered 175 mg/m² IV as specified in the treatment arm<br>Drug: Cisplatin<br>* Administered 75 mg/m²/day IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Administered AUC 5 as specified in the treatment arm<br>|
| Experimental: Squamous NSCLC Cohort B<br>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. | Drug: Tislelizumab<br>* Administered 200 mg intravenously (IV) as specified in the treatment arm<br>* Other names: BGB-A317;Drug: Gemcitabine<br>* Administered 1250 mg/m² IV as specified in the treatment arm<br>Drug: Cisplatin<br>* Administered 75 mg/m²/day IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Administered AUC 5 as specified in the treatment arm<br>|
| Experimental: SCLC<br>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. | Drug: Etoposide<br>* Administered 100 mg/m2 IV as specified in the treatment arm<br>Drug: Cisplatin<br>* Administered 75 mg/m²/day IV as specified in the treatment arm<br>Drug: Carboplatin<br>* Administered AUC 5 as specified in the treatment arm<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The objective response rate (ORR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of adverse events (AEs) according to NCI-CTCAE Version 4.03 |  | Up to 4 years | 
| 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 |  | Up to 4 years | 
| 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 |  | Up to 4 years | 
| Disease Control Rate (DCR) - defined as the proportion of participants who achieve CR, PR and SD using RECIST v1.1 |  | Up to 4 years | 
| Pharmacokinetic evaluations of BGB-A317 in combination with chemotherapy: including but not limited to Ctrough |  | Up to 4 years | 
| Anti-BGB-A317 antibody: immunogenic responses to BGB-A317 will be assessed to determine occurrence of anti-drug antibody. |  | Up to 4 years | 
| The abnormality of laboratory tests according to NCI CTCAE Version 4.03 |  | Up to 4 years |