DZD9008, a targeted therapy for EGFR exon20 insertion-mutant non-small cell lung cancer, appeared safe and efficacious, according to findings from early trials presented at the 2021 ASCO Annual Meeting.

“There are no approved targeted therapies for EGFR exon20 insertion (exon20ins) mutant NSCLC,” James Chih-Hsin Yang, PhD, MD, director of oncology at National Taiwan University Hospital, Taipei, and colleagues wrote in an abstract presented at the conference. “DZD9008 is a rationally designed selective, irreversible EGFR exon20ins inhibitor being studied in two ongoing phase 1/2 studies.”

The researchers treated 97 patients with NSCLC and either EGFR or HER2 mutations with DZD9008 once daily at doses ranging from 50 mg to 400 mg. Most patients (n = 53) were female. Fifty-nine patients had EGFR exon20 insertion mutations, and of these, 56 underwent more than one post-treatment assessment. The patients had received a median of two prior therapies, most of whom (92.9%; n =52 of 56) received chemotherapy. Nearly half (44.6%; n = 25 of 56) had received prior TKI therapy.

DZD9008 appeared well-tolerated up to a 400-mg dosage, the researchers reported. Cardiac arrhythmia and diarrhea were dose-limiting toxicities. 

Yang and colleagues reported that they observed partial responses at doses of 100 mg or greater. The objective response rate with a recommended phase 2 dose of 300 mg was 48.4%. The disease control rate among these patients was 90.3%.

Patients received treatment for a median of 100 days (range, 1-422) by the time of data cut-off. The longest duration of treatment surpassed 6 months, and at the time the abstract was published, 18 of 22 patients who responded to the drug were still responding. DZD9008 demonstrated anti-tumor activity in a variety of EGFR exon20 insertion mutations, the researchers reported

“DZD9008 showed a favorable safety profile and promising anti-tumor efficacy in pre-treated NSCLC with EGFR exon20ins mutations,” Yang and colleagues wrote.

The drug is now in phase 2 of study.

Disclosures: Yang reports honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche and Takeda; consulting or advisory roles with Abbvie, Amgen, Astellas Pharma, AstraZeneca, AstraZeneca (Inst), Bayer, Blueprint Medicines, Boehringer Ingelheim, Boehringer Ingelheim (Inst), Bristol-Myers Squibb, Celgene, Clovis Oncology, Daiichi Sankyo, G1 Therapeutics, Hansoh, Incyte, Lilly, Merck Serono, MSD Oncology, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda and Yuhan; and travel, accommodations and expenses from Pfizer. Please see the abstract for a complete list of all authors’ relevant financial disclosures.