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

NCT03432598 | Completed Phase 2

• 2 other identifiers: BGB-A317-206CTR20170361
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

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.

Conditions

Locally Advanced Lung Cancer; Metastatic Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (4)

Non-squamous NSCLC

EXPERIMENTAL

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; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin

Squamous NSCLC Cohort A

EXPERIMENTAL

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; Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin

Squamous NSCLC Cohort B

EXPERIMENTAL

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; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

SCLC

EXPERIMENTAL

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; Drug: Cisplatin; Drug: Carboplatin

Interventions

Tislelizumab DRUG

Administered 200 mg intravenously (IV) as specified in the treatment arm

Also known as: BGB-A317

Non-squamous NSCLC; Squamous NSCLC Cohort A; Squamous NSCLC Cohort B

Paclitaxel DRUG

Administered 175 mg/m² IV as specified in the treatment arm

Squamous NSCLC Cohort A

Gemcitabine DRUG

Administered 1250 mg/m² IV as specified in the treatment arm

Squamous NSCLC Cohort B

Etoposide DRUG

Administered 100 mg/m2 IV as specified in the treatment arm

SCLC

Pemetrexed DRUG

Administered 500 mg/m² IV as specified in the treatment arm

Non-squamous NSCLC

Cisplatin DRUG

Administered 75 mg/m²/day IV as specified in the treatment arm

Non-squamous NSCLC; SCLC; Squamous NSCLC Cohort A; Squamous NSCLC Cohort B

Carboplatin DRUG

Administered AUC 5 as specified in the treatment arm

Non-squamous NSCLC; SCLC; Squamous NSCLC Cohort A; Squamous NSCLC Cohort B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (7)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Beijing Chest Hospital, Capital Medical University

Beijing, Beijing Municipality, 101149, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Related Publications (1)

• 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.

  PMID: 32769013 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms

Interventions

tislelizumab; Paclitaxel; Gemcitabine; Etoposide; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Study Officials

• Jie Wang, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2018
• First Posted: February 14, 2018
• Study Start: August 24, 2017
• Primary Completion: February 25, 2019
• Study Completion: December 21, 2020
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (7)