CASPIAN is a Phase 3, open-label study of 1L platinum-etoposide (EP) ± durvalumab (D) ± tremelimumab (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.
Treatment-naïve pts with ES-SCLC were randomised 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + 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.
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 anti-drug 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).
| D+EP (n=265) | EP (n=266) | |||||
| imAE (group term)* | Any grade, n (%) | Grade ≥3, n (%) | Median time to onset,† days (range) | Any grade, n (%) | Grade ≥3, n (%) | Median time to onset,† days (range) |
| Any imAE | 52 (20) | 13 (5) | – | 7 (3) | 2 (1) | – |
| Hypothyroid | 24 (9) | 0 | 141 | 2 (1) | 0 | 63 |
| Hyperthyroid | 14 (5) | 0 | 85.5 | 0 | 0 | – |
| Pneumonitis | 7 (3) | 2 (1) | 191 | 2 (1) | 2 (1) | 177 |
| Hepatic | 7 (3) | 6 (2) | 93 | 0 | 0 | – |
| Dermatitis/rash | 4 (2) | 0 | 33.5 (16–91) | 2 (1) | 0 | 31 (27–35) |
| Diarrhoea/colitis | 4 (2) | 1 (0.4) | 28 (9–114) | 1 (0.4) | 0 | 64 |
| Thyroiditis | 4 (2) | 0 | 144 | 0 | 0 | – |
| Type 1 diabetes | 4 (2) | 4 (2) | 104 (38–316) | 0 | 0 | – |
*imAEs with incidence ≥2% in either arm are shown. †Time from first dose to onset of any grade imAEs.
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.
NCT03043872 (release date: February 6, 2017)
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca