D-0316 Shows Clinically Meaningful Improvement in Patients with T790M+ and EGFR+ NSCLC


More than half of patients with T790M-positive non-small cell lung cancer had a response to the third generation EGFR TKI D-0316 in a phase 2 study.

D-0316 showed clinically meaningful efficacy in patients with EGFR T790M-positive non–small cell lung cancer (NSCLC) who progressed on prior treatment according to an analysis of phase 2 study results presented at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.1

The third generation EGFR tyrosine kinase inhibitor [TKI] D-0316 is selective for EGFR-TKI and T790M resistance mutations in patients with NSCLC, which most patients will develop a resistance too after frontline treatment with first- and second-generation EGFR-TKIs. The single-arm phase 2 study (NCT03861156) of D-0316 looked at 290 patients who previously progressed on first line EGFR-TKI treatment and had T790M mutation in their tumor.

Patients from China first enrolled on the study (n = 176) were given 50 mg of D-0316, which saw an objective response rate (ORR) of 51.1% (95 CI, 43.3-58.7) when first assessed in 2019, but the dosage was altered to 75-100 mg after a 21-day lead in on treatment. The ORR of the 290 patients that fulfilled enrollment was 64.8% (95% CI, 59-70.3) and a disease control rate (DCR) of 95.2% (95% CI, 92-97.3), which met the primary endpoints of the study. Median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were premature at the time of the conference.

D-0316 also had a favorable response in subgroups of the study, according to researchers, who looked at 105 patients with central nervous system (CNS) metastases. The ORR among this group was 52.9% (95% CI, 35.1-70.2) for patients that had the higher dose in comparison to an ORR of 20% (95% CI, 4.3-48.1) for patients who had 50 mg of D-0316. PFS was also not reached in this group. Among 34 patients who had brain metastases at the baseline of the study 18 of these patients achieved a partial response on the therapy. After a median follow-up of 5.5 months, investigators also saw that 188 patients had a confirmed partial response by an independent review committee.

“The median duration of exposure in the 75-100mg cohort was 20.6 weeks,” explained Shun Lu, MD, lead investigator from the Shanghai Chest Hospital, in a virtual presentation at the virtual AACR Meeting 2021.“The investigator-assessed median PFS was 9.7 months and the median (iPFS) was 10.3 months.” In comparison to the 50 mg cohort, Lu added, the median PFS was 8.4 months and median iPFS was 8.6 months.

The median age of patients in the 75-100 mg cohort was 62.5 years old and 65.5% of patients were female.1 Patients with an ECOG performance status of 1 or 2 were accepted on the trial, with a majority of patients (78.6%) having a performance status of 1. Overall, 154 patients with stage 4a NSCLC and 299 patients with stage 4b NSCLC were observed on the study between both cohorts. The most common EGFR mutation with T790M was 19Del (67%) followed by patients whose tumor had 21-L858R (32%).

Treatment-related adverse effects (TRAEs) were observed on the study, but the most common were grades 1 and 2. The most common of these TRAEs included thrombocytopenia (57.2%), headache (27.6%), leukopenia (23.4%), anemia (22.1%), and rash (20.7%). The most common TRAE at grade 3 or higher was also thrombocytopenia (11.7%), other grade 3 TRAEs included pulmonary embolism (4.1%), electrolyte imbalance (2.1%), leukopenia (1.9%), and rash (1.3%). One death was due to TRAE (interstitial lung disease) and 6 patients were observed with interstitial lung diseases (2.1%).

“The investigator ORR of 52.9%, suggested that D-0316 showed clinical meaningful efficacy against CNS metastases and the study demonstrated potentially improved efficacy, with manageable toxicities, of D-0316 therapy,” Lu concluded.


Shun L, Zhang Y, Zhang G, et al. D-0316 in patients with advanced T790M-positive EGFR-mutant non-small cell lung cancer who progressed on prior EGFR-TKI therapy: results from a phase II study. Abstract presented at: American Association for Cancer Research Virtual Annual Meeting 2021; April 10-12, 2021; Virtual. Abstract CT170

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