LBA2 First-line durvalumab plus platinum-etoposide in extensive-stage (ES)-SCLC: Safety, pharmacokinetics (PK) and immunogenicity in CASPIAN

Abstract

Background: CASPIAN is a phase 3, open-label study of 1L platinum-etoposide (EP) 6durvalumab (D)6tremelimumab (T) for pts with ES-SCLC. D+EP significantly improved OS vs EP alone (HR 0.73 [95% CI 0.59-0.91]; p=0.0047) at a planned interim analysis. Rates of all-cause AEs and AEs leading to discontinuation were similar between arms. Immune-mediated AEs (imAEs) were higher with D+EP vs EP, while numerically fewer pts in the D+EP arm had serious AEs (SAEs; 30.9 vs 36.1%). Here we present further safety, PK and immunogenicity results. Methods: Treatment-naïve pts with ES-SCLC were randomised 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75mg + EP q3w, or EP q3w. Investigator's choice of carboplatin or cisplatin was allowed. In the IO arms, pts received 4 cycles of EP, followed by D 1500 mg q4w until progression; up to 6 cycles of EP and optional PCI were permitted in the control arm. Safety, PK and immunogenicity were secondary endpoints. Results: 265 pts received D+EP and 266 received EP. Serum concentrations were within the expected range for D and were similar across both arms for EP. Of 201 antidrug antibody (ADA)-evaluable pts in the D+EP arm, 11 (5.5%) were+ve for ADA to D at baseline only; no pts were +ve for treatment-emergent ADA or neutralising antibodies. The most common AEs, grade 3/4 AEs and SAEs in both arms were haematological toxicities. These were well managed using standard therapies per local practice; colony stimulating factor use was 50.4% in the D+EP arm and 56.9% in the EP arm, and 12.7% and 20.8% received blood transfusions. When events that coincided with cycles 5 and 6 of EP in the control arm were removed, the overall SAE rate was similar between arms (30.9% for D+EP vs 30.1% for EP). Most imAEs were low grade, endocrine-related and managed with corticosteroid or endocrine therapy; median time to onset was generally >60 days (table). Conclusion: In CASPIAN, the incidence of ADA to D was low and the safety profile of D+EP was consistent with previous reports of both D and EP. (Table Presented) .