Dizal today announced that sunvozertinib has been approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations, whose disease has progressed on or after platinum-based chemotherapy.

...U.S. Food and Drug Administration ("FDA") has granted Breakthrough Therapy Designation (BTD) to its sunvozertinib as the first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations.

Dizal Pharmaceutical Co., Ltd. (SHEX:688192) ("Dizal"), today announced that the U.S. Food and Drug Administration ("FDA") has granted Breakthrough Therapy Designation to DZD9008 (Sunvozertinib) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

...Patient who has progressed or intolerant to standard therapy (except treatment naïve patient with EGFR Exon20ins in Cohort 4)....

...If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspect of the study.Part A of the study (Phase I):Dose escalationPatients must have documented histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations, and have relapsed from, been refractory to or are intolerant to prior standard therapy without preferred alternative therapy.Dose expansionDose expansion cohort 1 and cohort 2: NSCLC patients with EGFR Exon20ins or HER2 Exon20ins, who have relapsed from, been refractory to or are intolerant to at least one line of prior systemic therapy.Dose expansion cohort 3 and cohort 4: NSCLC patients with EGFR Exon20ins, who have relapsed from, been refractory to or are intolerant to at least one line of prior systemic therapy.Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have not received prior systemic therapy (treatment naïve).Dose expansion cohort 6: NSCLC patients with EGFR Exon20ins, who have recevied at least one line of prior systemic therapy, and must have relapsed from, been refractory to or intolerant to Amivantamab treatment.Part B of the study (Phase II):Patients must have histologically or cytologically confirmed locally advanced or metastatic NSCLC with EGFR Exon20ins which is confirmed by central laboratory using an analytically validated next generation sequencing-based assay in archived tumor samples (if a patient has more than one FFPE blocks, the most recent tissue is preferred) or any fresh tumor biopsies (if archived tumor sample is not available) prior to the study entry. ...

...Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have...

...Adequate tumor tissue available, for central laboratory confirmation of EGFR exon 20 insertion mutation 4....

...Tumor tissue EGFR exon 20 insertion mutations confirmed by qualified local laboratories or sponsor-designated central laboratories....

Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy….In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile.

In the 1st line setting, sunvozertinib as monotherapy demonstrated promising anti-tumor efficacy and acceptable safety profile in NSCLC patients with EGFR exon20ins.

As of 17 October 2022, ORRs of subjects with positive EGFRexon20ins in tumor tissue and plasma ctDNA were 59.8% and 63.0%, respectively, comparable to the ORR (60.8%) of the whole efficacy population...The EGFRexon20ins concordance between tumor tissue-based and plasma ctDNA testing is high. Antitumor activity of sunvozertinib was robust regardless of tumor tissue-based or plasma ctDNA tests.

By the data cutoff date (October 17, 2022), the BICR assessed confirmed ORR (cORR) was 60.8% (59/97). In patients with baseline brain metastasis, the cORR was 48.5% (15/31)….The first pivotal study results confirmed sunvozertinib’s superior anti-tumor efficacy than the current available therapy for NSCLC with EGFR exon20ins.

Consistent with second line results, sunvozertinib demonstrated promising efficacy and safety profile as monotherapy in the first line setting for patients with advanced EGFR exon20ins NSCLC. .

WU-KONG6 is a phase 2, multi-center pivotal study in China in advanced NSCLC with EGFR exon20ins, whose diseases had progressed on or after platinum-based chemotherapy…the BICR evaluated confirmed ORR (cORR) was 59.8% (58/97). In patients with baseline brain metastasis, the cORR was 48.5% (16/33). Median DoR was not mature. Anti-tumor efficacy was observed across 30 different mutation subtypes....The first pivotal study results confirmed sunvozertinib's superior anti-tumor efficacy.

...56 locally advanced or metastatic NSCLC patients with EGFR Exon20ins mutations were enrolled…Anti-tumor activity was observed in patients with different categories of prior treatment….The data suggest sunvozertinib is active in NSCLC patients with EGFR Exon20ins, irrespective of categories of prior treatment.

...the safety and efficacy of sunvozertinib in platinum-pretreated advanced NSCLC patients harboring EGFR Exon20ins...Partial response was observed at ≥ 100 mg. At the dose level of 100 mg, 200 mg, 300 mg and 400 mg, confirmed ORR was 50% (1/2), 55.6 % (5/9), 44.8% (13/29) and 22.2% (2/9), respectively....The data suggest sunvozertinib is active in platinum-pretreated patients with EGFR Exon20ins, irrespective of prior or after anti-PD(L)1 treatment.

In the two ongoing phase 1 clinical studies, sunvozertinib was tolerated up to 400 mg once daily….Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFR exon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis.

Fifty-six patients with >16 different EGFR exon20ins mutations had >1 post-treatment efficacy assessment….Partial response was observed at ≥ 100 mg dose levels. At the RP2D dose of 300 mg once daily, the objective response rate was 48.4% (15/31), and disease control rate (DCR) was 90.3% (28/31)....Anti-tumor activity was observed across different EGFR exon20ins mutation subtypes....DZD9008 showed a favorable safety profile and promising anti-tumor efficacy in pre-treated NSCLC with EGFR exon20ins mutations.