Lee Chee Khoon, Liao Bin-Chi, Subramaniam Shalini, Chiu Chao-Hua, Mersiades Antony J, Ho Chao-Chi, Brown Chris, Lai Chun-Liang, Hughes Brett G M, Yang Tsung-Ying, O'Byrne Ken, Luo Yung-Hung, Yip Sonia, Ho Ching-Liang, Bray Victoria, Su Wu-Chou, Moore Melissa, Feng Wei-Lien, Bai Ya-Ying, Ford Kate, Cummins Michelle M, Stockler Martin R, Solomon Benjamin J, John Thomas, Chih-Hsin Yang James
NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
National Taiwan University Hospital, Taipei, Taiwan.
JTO Clin Res Rep. 2024 Nov 22;6(2):100771. doi: 10.1016/j.jtocrr.2024.100771. eCollection 2025 Feb.
-mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs).
Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) exon 20 T790M negative (T790M-, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), and (2) T790M positive (T790M+, progressing on greater than or equal to 1 lines of TKI, including osimertinib). The primary endpoint was the confirmed objective response rate (ORR) assessed by the investigators. Progression-free survival and safety were secondary outcomes.
One hundred participants from Australia and Taiwan were enrolled. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M- and T790M+, respectively. The ORR for T790M- was 31% (95% confidence interval: 20-45), including two complete responses. The ORR for T790M+ was 21% (95% confidence interval: 12-34). Median durations of response were 9.5 months and 6.3 months for T790M- and T790M+, respectively; median progression-free survival rates were 6.5 months and 4.9 months, respectively. For T790M-, ORR was 27% for 50% or higher PD-L1 (n = 22) and 0% for less than 50% PD-L1 (n = 10), respectively. For T790M+, ORR was 17% for 50% or higher PD-L1 (n = 24). The safety profile was consistent with previous reports.
Durvalumab, tremelimumab, and platinum-pemetrexed had modest anti-tumor activity in mutant NSCLC after progression on TKI. The T790M- cohort had higher ORR and a longer duration of response. Immune adverse events were not increased with tremelimumab. The clinical registration number of this trial is NCT03994393.
-突变型非小细胞肺癌（NSCLC）与低突变负荷和低水平的程序性死亡受体配体1（PD-L1）表达相关。我们开展了一项2期试验，以确定度伐利尤单抗、曲美木单抗和铂类培美曲塞在表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）治疗进展后的-突变型NSCLC中的疗效。
参与者接受诱导期度伐利尤单抗、曲美木单抗和铂类培美曲塞治疗，随后接受度伐利尤单抗-培美曲塞维持治疗。参与者分为两个队列：（1）外显子20 T790M阴性（T790M-，在一线奥希替尼或单一线程的第一代/第二代TKI治疗中进展），以及（2）T790M阳性（T790M+，在大于或等于1线TKI包括奥希替尼治疗中进展）。主要终点是研究者评估的确认客观缓解率（ORR）。无进展生存期和安全性为次要结局。
来自澳大利亚和台湾的100名参与者入组。中位随访时间为26个月，T790M-和T790M+分别有88%和96%经历疾病进展事件。T790M-的ORR为31%（95%置信区间：20-45），包括2例完全缓解。T790M+的ORR为21%（95%置信区间：12-34）。T790M-和T790M+的中位缓解持续时间分别为9.5个月和6.3个月；中位无进展生存率分别为6.5个月和4.9个月。对于T790M-，PD-L1为50%或更高（n = 22）时ORR为27%，PD-L1低于50%（n = 10）时ORR为0%。对于T790M+，PD-L1为50%或更高（n = 24）时ORR为17%。安全性概况与既往报告一致。
度伐利尤单抗、曲美木单抗和铂类培美曲塞在TKI治疗进展后的-突变型NSCLC中具有适度的抗肿瘤活性。T790M-队列的ORR更高且缓解持续时间更长。曲美木单抗未增加免疫不良事件。本试验的临床注册号为NCT03994393。
