Voice of China's novel third-generation EGFR-TKI SH-1028 in second-line therapy for EGFR T790M mutation-positive NSCLC

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At present, the third generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) available in China mainly includeOsimertinib,AmetinibandFumetinib, both significantly prolonged EGFR-positive mutationsnon-small cell lung cancer(NSCLC), but there are other issues such as drug resistance and safety, and there is still room for optimization in the design of third-generation EGFR TKIs

background

EGFR TKIs are the standard first-line treatment for patients with EGFR-mutant NSCLC

method

This study is a multicenter, single-arm, open-label Phase II clinical trial (NCT03823807)

result

A total of 286 patients with EGFR T790M mutation-positive advanced NSCLC were enrolled in this study, of which 59 and 227 patients were enrolled in part A and part B, respectively

As of September 17, 2021, there were 1, 32, and 24 patients with complete remission (CR), partial remission (PR) and stable disease (SD) assessed by IRC in Part A, respectively, ORR was 55.

In Part B of this study, there were 137 and 68 patients with PR and SD, respectively, assessed by IRC, ORR was 60.

Figure 1.
Waterfall plot of optimal percent change in target lesion size from baseline

Figure 2 Survival analysis

Subgroup analysis of the ORR data in Part B found that the ORR of the EGFR exon 19 deletion group (71.
5%) was significantly higher than that of the EGFR L858R mutation group (36.
2%) (P < 0.
001) (Figure 3); EGFR exon The median PFS of patients with 19 deletion was 13.
8 months, which was better than 9.
7 months of patients with EGFR L858R mutation (Fig.
2C)
.
The ORR of patients with brain metastases (53.
8%) was lower than that of patients without brain metastases (63.
9%) (P=0.
134)
.

Figure 3 ORR subgroup analysis

In terms of safety, among 286 patients, 44 patients reported at least one treatment-related adverse event of grade 3 or higher, the most common being increased serum creatine phosphokinase (13 patients, 4.
5%),diarrhea(6 cases, 2.
1%) and QT interval prolongation (3 cases, 1.
0%)
.
26 (9.
1%) patients experienced treatment-relatedrash, both are Level 1 or Level 2
.
This study has not yet appearedInterstitial lung disease
.

in conclusion

The novel third-generation EGFR-TKI SH-1028 showed favorable efficacy and safety in patients with locally advanced or metastatic NSCLC with EGFR T790M mutation
.
SH-1028 is expected to become a new option for second-line treatment of advanced NSCLC patients
.

references:

Xiong AW, Ren SX, Liu HM, et al.
Efficacy and safety of SH-1028 in patients with EGFR T790M positive non-small-cell lung cancer: a multicenter, single-arm, open-label, phase 2 trial.
J Thorac Oncol.
2022 Jul 4;S1556-0864(22)00327-6.
doi: 10.
1016/j.
jtho.
2022.
06.
013