Abstract 299P
Background
CASPIAN (NCT03043872) assessed D + 4 cycles of EP vs ≤6 cycles of EP in pts with ES-SCLC and established D + EP as a 1L standard of care. The phase IIIb LUMINANCE study (NCT04774380) assessed 1L D + ≤6 cycles of EP in pts with ES-SCLC. Primary safety and efficacy results were consistent with CASPIAN, including in pts who received ≥5 cycles of EP. We report final safety and efficacy results and selected exploratory biomarker analyses.
Methods
Pts (N=152) received D 1500 mg + EP Q3W for ≤6 cycles, followed by D Q4W until disease progression or unacceptable toxicity. Primary endpoints: incidence of grade ≥3 and immune-mediated adverse events (AE/imAE). Progression-free and overall survival (PFS/OS) were secondary endpoints. Exploratory biomarker analyses assessed the correlation of PFS/OS with baseline PD-L1 expression on tumour/immune cells, MHC I and CD8 by immunohistochemistry, and ctDNA detection and tumour methylated fraction (TMeF) by Cancer Research Solution (GRAIL, Inc.).
Results
At final data cutoff (21 April 2024; median follow-up 11.6 months) 13.2% of pts were still receiving D. Pts received a median (range) 9 (1–30) doses of D and 48.7% of pts had received 6 cycles of EP. Final safety and key efficacy results are shown (Table). 148 pts were evaluable for baseline ctDNA; TMeF was detected in 100% of samples. 96/76/71 pts were evaluable for MHC I/CD8/PD-L1. Low TMeF and high CD8 density at baseline were associated with longer PFS/OS (Table). High MHC I expression generally favoured longer PFS/OS; no specific cutoff was identified (PFS/OS HRs ranged from 0.54–0.83/0.48–0.87, cutoffs ranged from 5–95%). PD-L1 status was not clearly associated with PFS/OS (data will be presented).
Table 299POverall safety and efficacy
| All pts (N=152) | ||||
| Grade ≥3 AEs, n (%) | 91 (59.9) | |||
| imAEs, n (%) | 22 (14.5) | |||
| Grade 3/4 | 6 (3.9) | |||
| PFS (95% CI) | ||||
| Median, months | 6.3 (5.8–6.5) | |||
| 12-month, % | 15.0 (9.8–21.2) | |||
| OS (95% CI) | ||||
| Median, months | 16.4 (12.5–18.7) | |||
| 12-month, % | 59.8 (51.0–67.6) | |||
| 18-month, % | 43.9 (35.1–52.3) | |||
| PFS/OS by baseline ctDNA and CD8 density | ||||
| ctDNA-evaluable pts (n=148) | CD8-evaluable pts (n=76) | |||
TMeF low ConclusionsThese results further support the use of 1L D for ES-SCLC. Though limited by a lack of a control arm, PD-L1, MHC I and CD8 analyses were consistent with CASPIAN; ctDNA data support further investigation of the potential of TMeF as a biomarker in SCLC. Clinical trial identificationNCT04774380, release date 1st March 2021. Editorial acknowledgementMedical writing support for the development of this abstract, under the direction of the authors, was provided by Ella Spencer of Ashfield Medcomms (London, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureN. Reinmuth: Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim, MSD Oncology, Takeda, and Amgen; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Takeda, Amgen, Lilly, AbbVie, Merck KGaA, Sanofi Aventis GmbH, and Janssen Oncology; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Takeda, Amgen, Lilly, AbbVie, Merck KGaA, Sanofi Aventis GmbH, and Janssen Oncology. N. Leighl: Financial Interests, Institutional, Research Grant: AstraZeneca. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Pfizer, Novartis, Astellas, BMS, MSD, Lilly, Gilead, Takeda. E. Bria: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Pfizer, Takeda, Eli Lilly, BMS, Novartis, Celltrion, Daiichi Sankyo, Johnson & Johnson; Financial Interests, Institutional, Funding: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Roche, Pfizer, Takeda, Eli Lilly, BMS, Novartis, Daiichi Sankyo. I. Cicin: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Eli Lilly, F. Hoffmann-La Roche, MSD, AbbVie and Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Eli Lilly, F. Hoffmann-La Roche, MSD, AbbVie and Pfizer, Abdiibrahim, Nobel, Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Merck Serono, MSD, Parexel, Pfizer, Quintiles, AbbVie and Taiho. S. Kilickap: Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Other, Steering committee member: Regeneron. S. Novello: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Daiichi Sankyo, BeiGene, Janssen, Amgen, Roche, Lilly, Takeda; Financial Interests, Personal, Advisory Role: BeiGene, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, AMG, BeiGene, MSD, Roche, Novartis, Daiichi Sankyo, Takeda, Pfizer, Roche, Thermo Fisher; Financial Interests, Personal, Other, Steering committee member: Janssen. S. Lang: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca. U. Emeribe, Y. Shrestha: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Xie, N. Donner: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. F. de Marinis: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD Oncology, Bristol Myers Squibb, Roche/Genentech, Pfizer, Novartis, Takeda, Daiichi Sankyo, Merck Serono. All other authors have declared no conflicts of interest. This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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