Abstract 136P
Background
Treatment option is limited for EGFR-mutated NSCLC after failure to EGFR TKIs. This multicenter, open-label, phase II study aims to evaluate the efficacy and safety of TIS plus chemo (cohort 1) or TIS plus chemo and bevacizumab (cohort 2) in EGFR-mutated nsq-NSCLC pts failed to EGFR TKI therapies. Herein, the primary analysis of cohort 1 is reported.
Methods
In cohort 1, pts with EGFR sensitizing mutations who had failed prior EGFR-TKIs received TIS plus carboplatin and nab-paclitaxel (induction), followed by TIS plus pemetrexed (maintenance). Primary endpoint was 1-year PFS rate; the planned sample size was 66 with a historical control of 7% (chemo), an expected value of 20%, one-sided α of 0.05, and power of 85%.
Results
From Jul 2020 to Dec 2021, 69 pts were enrolled; 39 pts (56.5%) harbored EGFR exon 19del; 28 pts (40.6%) had exon 21 L858R. 34 pts (49.3%) had progression on both 1st /2nd and 3rd EGFR-TKIs. As of 30 Jun 2022 (median follow-up, 8.2 months), 23.2% (n=16) of pts remained on treatment. Among 62 pts in EAS (Table), the confirmed ORR and DCR were 50.0% (95% CI 37.0-63.0%) and 87.1 % (95% CI 76.1-94.3%), respectively. Median PFS was 7.6 (95% CI, 6.4-9.8) months, with a 1-year PFS rate of 23.8% (90% CI, 13.1-36.2%). Pts with L858R mutation or having prior 1st/2nd EGFR-TKIs tended to have a longer PFS compared with pts with EGFR exon 19del mutation or progressed on 1st /2nd and 3rd EGFR-TKIs. Median OS was not reached (95% CI, 14.0-NE), and 1-year OS rate was 74.5% (95% CI, 56.5-86.0%). Safety profile was consistent with previous reports of TIS plus chemo in pts with EGFR-wt NSCLC. Grade 3-4 TEAEs occurred in 40.6% (28/69) of pts. 27.5% (19/69) of pts experienced irAEs; grade 3-4 irAEs occurred in 5 (7.2%) pts. Table: 136P
| EAS (Efficacy analysis set∗, n=62) | |
| BOR | |
| PR | 35 (56.5) |
| SD | 19 (30.6) |
| PD | 7 (11.3) |
| NA | 1 (1.6) |
| Confirmed ORR, % (95% CI) | 50.0 (37.0, 63.0) |
| DCR, % (95% CI) | 87.1 (76.1, 94.3) |
| Median TTR, months (range) | 1.70 (1.2, 7.7) |
| Median DOR, months (95% CI) | 6.1 (4.7, 10.3) |
| Median PFS, months (95% CI) | 7.6 (6.4, 9.8) |
| 1-year PFS rate, % (90% CI) | 23.8 (13.1, 36.2) |
| Median OS, months (95% CI) | NR (14.0, NE) |
| 1-year OS rate, % (95% CI) | 74.5 (56.5, 86.0) |
∗Included pts receiving ≥1 dose of TIS or chemo, and having completed ≥1 post-treatment tumor assessment unless treatment was discontinued before the first tumor assessment due to disease progression or death; NA, not accessible; NR, not reached; NE, not estimable.
Conclusions
The study met the primary endpoint for cohort 1. TIS plus chemo is effective with acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.
Clinical trial identification
NCT04405674.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Han: Financial Interests, Institutional, Research Grant: AstraZeneca, BeiGene, Roche, Innovent Biologics, Chia Tai Tianqing Pharmaceutical. All other authors have declared no conflicts of interest.