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

BeiGene

Status and phase: Completed; Phase 2

Conditions: Locally Advanced Lung Cancer; Metastatic Lung Cancer

Treatments: Drug: Cisplatin; Drug: Etoposide; Drug: Gemcitabine; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Tislelizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03432598

CTR20170361 (Registry Identifier)

BGB-A317-206

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 4 patient groups

Non-squamous NSCLC

Experimental group

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.

Treatment:

Drug: Tislelizumab

Drug: Pemetrexed

Drug: Carboplatin

Drug: Cisplatin

Squamous NSCLC Cohort A

Experimental group

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.

Treatment:

Drug: Tislelizumab

Drug: Carboplatin

Drug: Paclitaxel

Drug: Cisplatin

Squamous NSCLC Cohort B

Experimental group

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.

Treatment:

Drug: Tislelizumab

Drug: Carboplatin

Drug: Gemcitabine

Drug: Cisplatin

SCLC

Experimental group

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.

Treatment:

Drug: Carboplatin

Drug: Etoposide

Drug: Cisplatin