TPS8586 Background: SCLC accounts for ~13% of all lung cancers and is characterized by rapid growth and early metastases development. Standard of care CT for pts presenting with ED-SCLC is associated with the development of resistance, leading to poor treatment outcomes. As such, new therapies are needed. The high mutation burden associated with SCLC provides a rationale for investigating immune checkpoint blockade in this tumor type. D is a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. T is a selective human IgG2 mAb against CTLA-4. D alone and in combination with T has demonstrated a manageable safety profile and encouraging antitumor activity in non-small cell lung cancer (NSCLC). D ± T in combination with CT has also shown acceptable tolerability and preliminary signs of clinical activity in advanced NSCLC and thus may provide benefit in SCLC. Methods: CASPIAN (NCT03043872) is a Phase 3, randomized, multicenter, open-label, global study to determine the efficacy of CT in combination with D ± T as first-line treatment in ED-SCLC (Stage IV). Treatment-naïve pts (N = ~795; WHO/ECOG PS 0 or 1) will be randomized 1:1:1 to receive D (1500 mg) + T (75 mg) i.v. every 3 weeks (q3w) + CT (Arm 1); D (75 mg) i.v. q3w + CT (Arm 2); or CT alone (Arm 3). D ± T will be concurrently administered with CT in Arms 1 and 2 and will continue post-CT (1 further dose for T; until confirmed progressive disease for D). CT (etoposide [80–100 mg/m2] i.v. on Days 1–3 q3w + carboplatin [AUC 5–6] i.v. on Day 1 q3w or cisplatin [75–80 mg/m2] i.v. on Day 1 q3w) will be given for up to 4 cycles in Arms 1 and 2 and up to 6 cycles in Arm 3. The co-primary endpoints are overall survival (OS) and progression-free survival (PFS) using blinded independent central review (RECIST v1.1), for Arm 1 vs Arm 3. Secondary endpoints include OS and PFS for Arm 2 vs Arm 3 and Arm 1 vs Arm 2, ORR, OS at 18 months, proportion of patients alive and progression free at 6 and 12 months, PK, immunogenicity, HRQoL, and safety and tolerability. Exploratory endpoints include PFS after subsequent anticancer therapy and correlation of biomarkers with response to treatment. Recruitment is ongoing. Clinical trial information: NCT03043872.
481TiP Pembrolizumab (MK-3475) versus platinum-based chemotherapy for PD-L1+ non-small cell lung cancer (NSCLC): Randomized, open-label, phase 3 KEYNOTE-042 study
