Dizal (Jiangsu) Pharmaceutical Co., Ltd. presented compelling data of its robust oncology portfolio at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2 to 6, 2023, in Chicago. Highlights include new or updated findings from Dizal's leading assets sunvozertinib (a selective EGFR TKI targeting a wide spectrum of EGFR mutations) and golidocitinib (a JAK1 only inhibitor), which have demonstrated superior efficacy in treating advanced non-small cell lung cancer (NSCLC) and relapsed and refractory peripheral T-cell lymphoma (r/r PTCL), respectively. Sunvozertinib cemented "Best-in-Class" position for NSCLC patients with EGFR Exon20ins mutations: NSCLC patients with EGFR Exon20 insertion (Exon20ins) mutations have worse clinical outcomes due to the absence of effective targeted therapies.

Sunvozertinib is a rationally designed, orally available, best-in-class tyrosine kinase inhibitor (TKI) that specifically targets these mutations. Its new drug application (NDA) has been accepted by the China National Medical Products Administration (NMPA) and granted priority review for the treatment of advanced NSCLC with EGFR Exon20ins mutations following platinum-based chemotherapies. With longer follow-up, sunvozertinib showed an unprecedented ORR of 60.8% in the second-line setting and beyond: Updated results of WU-KONG6, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR Exon20ins mutations, were presented in an oral session.

With longer follow-up, patients treated with sunvozertinib achieved a confirmed objective response rate (cORR) of 60.8% assessed by independent review committee (IRC). Anti-tumor efficacy was observed across a broad range of EGFR Exon20ins subtypes, and tumor response was also observed in patients with pretreated and stable brain metastasis. Nevertheless, WU-KONG6 study revealed that sunvozertinib had an impressive increase in ORR, reaching 60.8% in the = second-line treatment of EGFR Exon20ins NSCLC.

Additionally, sunvozertinib also demonstrated a high ORR regardless of mutation subtypes and insertion locations, as well as in patients with pre-treated and stable brain metastasis. These findings provide promising evidence for the treatment of EGFR Exon20ins NSCLC, and it is optimistic about sunvozertinib's potential in a broader realm of NSCLC. Sunvozertinib showedthe "Best-in-Class" potential with an ORR of 77.8% in the first-line setting: According to the pooled analysis from WU-KONG1 part A and WU-KONG15, sunvozertinib monotherapy demonstrated significant efficacy in the treatment-naive EGFR Exon20ins NSCLC patients, achieving a best objective response rate (BOR) of 77.8% in the 300 mg cohort.

In addition to expressive antitumor efficacies, sunvozertinib continues showing favorable overall safety profile, similar to other EGFR-TKIs. With its superior efficacy and manageable safety profile, sunvozertinib is poised to become a robust player in the realm of EGFR Exon20ins mutations. Sunvozertinib showed encouraging anti-tumor efficacy in advanced NSCLC patients after failure of EGFR TKI treatment: While EGFR-targeted therapy can provide a durable survival benefit to NSCLC patients with EGFR mutations, resistance invariably emerges to current generation EGFR inhibitors.

Findings of the pooled analysis from WU-KONG1 Part A, WU-KONG2 and WU-KONG15 revealed that sunvozertinib exhibited encouraging anti-tumor efficacy in NSCLC patients with common EGFR mutations who failed standard EGFR TKI treatment. A total of 37 heavily pretreated (median 5 lines of prior treatment) patients were treated with sunvozertinib, among whom 70.3% had previously received third-generation EGFR TKI, 91.9% received chemotherapy and 40.5% had baseline brain metastasis. At the data cut-off date of April 3, 2023, the median progression-free survival (mPFS) was 5.8 months, and the median duration of response (mDoR) was 6.5 months.

And the safety profile was consistent with previous reports. Golidocitinib yielded promising tumor responses in r/r PTCL: Relapsed or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive non-Hodgkin lymphoma with a five-year survival rate of less than 30%. Currently there is no consensus on the standard treatment for r/r PTCL.

New innovative treatment strategies are needed to improve survival in this patient population. Dizal identified that JAK/STAT may mediate the pathogenesis of PTCL and launched clinical studies of golidocitinib to test the hypothesis. Golidocitinib is the First-in-Class Janus kinase 1 (JAK1) only inhibitor currently being evaluated in a multinational, pivotal study in r/r PTCL (JACKPOT8 Part B).

Consistent with earlier data, golidocitinib demonstrated potent and durable anti-tumor efficacy in the pivotal study, with the presentation of clinical data delivered orally at 2023 ASCO. A total of 112 r/r PTCL patients were included in the analysis. IRC assessed ORR was 44.3% in 88 patients with PTCL including 21 complete responses (CRR, 23.9%).

Anti-tumor efficacy was observed across different PTCL subtypes. The mDoR has not been reached. The longest DoR was 16.8 months, and the patient is still responding.

The safety profile of golidocitinib was benign. The majority of treatment-related adverse events (TRAEs) were hematological in nature and amenable to monitoring and management in the clinical setting. The median relative dose intensity was 100%, and the longest treatment duration was 18 months.