Clinical trial NCT03432598: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced Lung Cancer; Metastatic Lung Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-02-14
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. Male or female, aged 18-75 years on the day of signing informed consent.
2. 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.
3. 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.
4. 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:

1. 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.
2. 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
3. Prior therapies targeting PD-1, PD-L1 or PD-L2

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: The objective response rate (ORR) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 4 years
Secondary outcomes:
measure: The incidence and severity of adverse events (AEs) according to NCI-CTCAE Version 4.03
timeFrame: Up to 4 years
measure: 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
timeFrame: Up to 4 years
measure: 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
timeFrame: Up to 4 years
measure: Disease Control Rate (DCR) - defined as the proportion of participants who achieve CR, PR and SD using RECIST v1.1
timeFrame: Up to 4 years
measure: Pharmacokinetic evaluations of BGB-A317 in combination with chemotherapy: including but not limited to Ctrough
timeFrame: Up to 4 years
measure: Anti-BGB-A317 antibody: immunogenic responses to BGB-A317 will be assessed to determine occurrence of anti-drug antibody.
timeFrame: Up to 4 years
measure: The abnormality of laboratory tests according to NCI CTCAE Version 4.03
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital, Capital Medical University
state: Beijing
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Jie Wang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.