2875 - A randomized non-comparative phase II study of anti–PD-L1 ATEZOLIZUMAB or chemotherapy as second-line therapy in patients with small cell lung cancer: Results from the IFCT-1603 Trial

Background

This randomized Phase II trial sought to evaluate the activity of the engineered PD-L1 antibody ATEZOLIZUMAB (ATZ), as systemic therapy of small cell lung cancer (SCLC) progressing after first line platinum – ETOPOSIDE based chemotherapy (CT).

Methods

Patients (pts) were randomly assigned 2:1 to ATZ, 1200 mg IV, every three weeks until progression or unacceptable toxicity, or conventional CT up to six cycles: i.e. second-line oral or IV TOPOTECAN or re-induction of CARBOPLATIN – ETOPOSIDE doublet (investigator choice based on center policy). Main eligibility criteria were performance status (PS) 0-2 and measurable disease (RECIST 1.1). We performed no selection on PD-L1 tissue expression. Patients receiving corticosteroid therapy, pts with autoimmune disease history and these with brain metastases were excluded. The primary endpoint was objective response rate (ORR) at 6 weeks (confirmation needed at 12 weeks).

Results

A total of 73 patients were randomized (ATZ n = 49; CT n = 24) between 03/2017 and 12/2017. One patient in the ATZ group did not receive any treatment. In the ATZ group, 83.7 % of the pts had PS 0-1, 79.6% had an extensive disease and 67.3 % had a sensitive relapse (progression after 90 days since the last dose of first line CT). At six weeks, in the ATZ group and eligible pts (n = 43), ORR was observed in 1 pt (2.3%, CI [0.0; 6.8]) and 8 other pts (18.6%, CI [7.0; 30.2]) had a stable disease. In the CT group and eligible pts (n = 21), 9.5% of the pts achieved an ORR and 52.4% had a stable disease. Progression-free survival were 1.4 months, CI [1.2; 1.5] in the ATZ group and 4.2 months CI [1.5; 5.9] in the CT group. At the time of reporting, 5 pts still benefit from a stable disease in the ATZ group versus none in the CT group. Two pts (4.2%) in the ATZ group experienced a grade 3 fatigue. Two pts developed grade 1 dysthyroidism.

Conclusions

IFCT-1603 trial did not show any efficacy or safety signals for single drug ATEZOLIZUMAB used as treatment in relapsed SCLC. Follow-up data will be updated and search for PD-L1 tissue expression and mutational tumor burden will be presented.

Clinical trial identification

NCT03059667.

Legal entity responsible for the study

IFCT (French Cooperative Thoracic Intergroup).

Funding

Roche.

Editorial Acknowledgement

N/A

Disclosure

L. Greillier: Grants, personal fees and non-financial support: Roche, outside the submitted work. C. Audigier Valette: Roche. D. Moro-Sibilot: Advisory board: Roche, Pfizer, AstraZeneca, BMS, MSD, Lilly, Boehringer, Abbvie, Takeda; Corporate-sponsored research: Boehringer Ingelheim, Abbvie. V. Gounant: AstraZeneca, Roche, Boehringer Ingelheim, BMS, Pfizer, Abbvie, MSD. P-J. Souquet: Grant, personnal fees, congress, board: Roche. All other authors have declared no conflicts of interest.