Abstract CT533: Durvalumab (D) plus tremelimumab (T) in platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC): Efficacy, safety and ctDNA dynamics from Arm A of the phase 2 BALTIC study
Authors: Reinmuth Niels , Juan-Vidal Oscar , Horváth Zsolt , Kowalski Dariusz , Kryzhanivska Anna , Csánky Eszter , Gálffy Gabriella , Bryl Maciej , Vicente David , Vynnychenko Ihor , Pápai-Székely Zsolt , Armstrong Jon , Dalvi Tapashi , Shrestha Yashaswi , Xie Mingchao , Jiang Haiyi , Bondarenko Igor 
Published: June 2022

Abstract
Background: Molecular response based on ctDNA dynamics may be predictive of benefit from immunotherapy in NSCLC, complementing radiologic disease assessment and potentially enabling early clinical decision-making, but data in SCLC are lacking. The phase 2, multi-arm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations in platinum-refractory/resistant ES-SCLC; we report efficacy, safety, and exploratory ctDNA and PD-L1 analyses from pts who received D + T in Arm A.
Methods: Eligible pts had ES-SCLC, progressive disease (PD) during or within 90 days of completing 1L platinum-based CT, WHO PS 0-1, and life expectancy ≥8 weeks. In Arm A, pts received D 1500 mg + T 75 mg q4w for 4 cycles, followed by maintenance D 1500 mg q4w until PD. The primary endpoint was ORR (investigator assessment, RECIST v1.1). Secondary endpoints included DCR, PFS, OS, and safety and tolerability. Prespecified exploratory analyses included assessment of baseline/on-treatment ctDNA levels measured by maximum variant allele frequency (MaxVAF), and PD-L1 expression on tumor cells (TC) and immune cells (IC) (VENTANA PD-L1 [SP263] Assay).
Results: 41 pts received treatment with D + T (median age 63 years; 76% male; 76% PS 1). At the data cut-off (DCO; Jun 22, 2020), median treatment duration was 12 weeks, with 3 pts ongoing D treatment (these pts had received ≥38, ≥21, and ≥19 doses of D, respectively, at DCO). Confirmed ORR was 7.3% (95% CI 1.54‒19.92; 3 partial responses [PR]). DCR at 12 weeks was 27%. 21 pts (51%) were PD-L1 evaluable. Of 12 pts with PD-L1 expression (TC or IC) ≥1%, 3 (25%) had a best response of PR or stable disease, compared with 1 (11%) of 9 pts with PD-L1 (TC or IC) &lt;1%. Median PFS was 1.84 mo (95% CI 1.77‒1.91) and median OS was 5.36 mo (95% CI 2.89‒7.23). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 8 pts (20%); TRAEs led to treatment discontinuation in 5 pts (12%) and death in 1 pt (hemorrhagic enterocolitis). 26 pts (63%) were evaluable for ctDNA at baseline, and 10 pts (24%) had on-treatment ctDNA data. Pts with baseline MaxVAF in low (n=9), medium (n=8), and high (n=9) tertiles had a median OS of 12.8, 4.5, and 2.3 mo, respectively. Pts with a decrease in on-treatment ctDNA level (delta MaxVAF &lt;0) had a longer median OS (12.0 mo) vs those with an increase (5.6 mo).
Conclusions: Although limited antitumor activity was observed in refractory/resistant ES-SCLC in BALTIC, association of lower baseline ctDNA levels (MaxVAF) with longer OS may reflect the prognostic effect of disease burden. Association of on-treatment reduction in ctDNA level with longer OS suggests potential use of ctDNA as a surrogate of treatment response in ES-SCLC. Further analyses in larger datasets and in a randomized setting are warranted.
Citation Format: Niels Reinmuth, Oscar Juan-Vidal, Zsolt Horváth, Dariusz Kowalski, Anna Kryzhanivska, Eszter Csánky, Gabriella Gálffy, Maciej Bryl, David Vicente, Ihor Vynnychenko, Zsolt Pápai-Székely, Jon Armstrong, Tapashi Dalvi, Yashaswi Shrestha, Mingchao Xie, Haiyi Jiang, Igor Bondarenko. Durvalumab (D) plus tremelimumab (T) in platinum-refractory/resistant extensive-stage small cell lung cancer (ES-SCLC): Efficacy, safety and ctDNA dynamics from Arm A of the phase 2 BALTIC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT533.