On September 17, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported subgroup analysis findings of its WU-KONG1 Part B (WU-KONG1B) study at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Dizal Pharma, SEP 17, 2024, View Source [SID1234646712]). The results showed promising anti-tumor efficacy of sunvozertinib in relapsed or refractory non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) across different baseline characteristics, underpinning its significant clinical value for this patient population around the globe.

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WU-KONG1B is an open-label, multinational pivotal study to investigate the efficacy and safety of sunvozertinib in relapsed or refractory NSCLC with EGFR exon20ins. The study is currently being conducted across 10 countries and regions in Asia, Europe, North America, and South America. WU-KONG1B met its primary endpoint, with the preliminary results featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, demonstrating the transformative potential of sunvozertinib as a single, oral agent to treat EGFR exon20ins NSCLC. Results of the subgroup analysis were presented on September 14 at the 2024 ESMO (Free ESMO Whitepaper) Congress in Barcelona, Spain.

As of March 22, 2024, a total of 107 patients with at least 33 EGFR exon20ins subtypes were included in the efficacy analysis set. The key findings were as follows:

Per independent review committee (IRC) assessment, target lesions shrinkage was observed in 92.4% (98/106) of patients.
Per IRC assessment, the best objective response rate (ORR) was 53.3%, including 3 complete response (CR).
By EGFR exon20ins region classification, the best ORR in near loop, far loop, C-helix and unknown were 51.9%, 59.1%, 66.7% and 40%, respectively.
IRC assessed ORR was comparable between different subgroups regardless of race, region, baseline disease characteristics and prior anti-cancer treatment history.

Race

Region

Baseline BM

Best Response, n (%)

Asian

(n = 62)

Non-Asian

(n = 45)

Asia

(n = 58)

Non-Asia

(n = 49)

With

(n = 27)

Without

(n = 80)

CR

3 (4.8)

0 (0.0)

3 (5.2)

0 (0.0)

0 (0.0)

3 (3.8)

PR

32 (51.6)

22 (48.9)

29 (50.0)

25 (51.0)

18 (66.7)

36 (45.0)

Prior Amivantamab treatment

Prior IO treatment

Best Response, n (%)

With

(n = 14)

Without

(n = 93)

With

(n = 52)

Without

(n = 55)

CR

0 (0.0)

3 (3.2)

2 (3.8)

1 (1.8)

PR

7 (50.0)

47 (50.5)

26 (50.0)

28 (50.9)

With median follow-up of 7 months, duration of response (DoR) was not reached, and 66.7% of responders were still responding.
The safety profile was similar to previously reported results, and clinically manageable.
"WU-KONG1B study enrolled more than 40% of non-Asian patients. The subgroup analysis suggested superior anti-tumor efficacies and well-tolerated safety profiles of sunvozertinib across EGFR exon20ins NSCLC patients with different baseline demographics and clinical characteristics on a global scale. We are intensifying our efforts to advance ongoing global pivotal studies and regulatory submissions of this FDA Breakthrough Therapy Designated asset, making available an effective and safe oral option to more patients around the world." said Xiaolin Zhang, PhD, CEO of Dizal.

WU-KONG28, a phase Ⅲ multinational randomized study, is ongoing to assess sunvozertinib versus platinum-based doublet chemotherapy as a first-line treatment in patients from 16 countries and regions in Asia, Europe, North America, and South America. The anticipated data of this study is expected to further improve outcomes of patients in this realm.

About sunvozertinib (DZD9008)

Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery (IF:39.397) and The Lancet Respiratory Medicine (IF: 76.2).