sunvozertinib (DZD9008) / Dizal Pharma - LARVOL DELTA

Efficacy of zipalertinib in NSCLC patients with EGFR exon 20 insertion mutations who received prior platinum-based chemotherapy with or without amivantamab. (ASCO 2025) - P1/2 | "Of the 51 pts with prior ami, 30 had no other ex20ins-directed therapy, while 21 had also received other ex20ins drugs (such as mobocertinib, sunvozertinib, BLU-451, or poziotinib), the cORR was 30.0% and 14.3%, respectively. Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in pts with exon20ins NSCLC who have received prior platinum-based chemotherapy and for those who received prior amivantamab, a significant and growing unmet need. BICR assessed tumor responses per RECIST v1.1.CR=complete response, PR=partial response, SD=stable disease."

Clinical • EGFR exon 20 • IO biomarker • Anemia • Dental Disorders • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

A real-world study on first-line (1L) treatment for 46 advanced lung adenocarcinoma patients harbouring epidermal growth factor 20 insertion mutation (EGFR ex20ins). (ASCO 2025) - P=N/A | "In NTT cohort, patients received sunvozertinib, furmonertinib or combination therapy of JMT101 and osimertinib. For advanced lung adenocarcinoma patients harbouring EGFR ex20ins, novel targeted drug-based therapies represented an effective treatment option and were well tolerated."

Clinical • EGFR exon 20 • Metastases • Real-world • Real-world evidence • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Cost-effectiveness Analysis of Sunvozertinib as a Second-line Treatment for Advanced Non-Small Cell Lung Cancer With EGFR exon20ins Mutation: An Economic Evaluation Based on MAIC (ISPOR 2025) - No abstract available

Clinical • Cost effectiveness • EGFR exon 20 • HEOR • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Cost-Effectiveness Analysis of Sunvozertinib as a Second-line Treatment for Advanced Non-Small Cell Lung Cancer with EGFR exon20ins Mutation: An Economic Evaluation Based on MAIC (ISPOR 2025) - "The comparator was set as the most commonly used treatment regimen (chemotherapy combined with bevacizumab) in the base case analysis, and as a real-world mixed treatment regimen including PD-1, EGFR-TKIs and chemotherapy in scenario analysis. Sunvozertinib presents a cost-effective regimen as a second-line treatment for NSCLC patients with EGFR exon20ins Mutation. The scenario analysis and sensitivity analysis verify the robustness of the base case result."

Clinical • Cost effectiveness • EGFR exon 20 • HEOR • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Efficacy and safety outcomes of emerging EGFR‑TKIs for patients with non‑small cell lung cancer with EGFR exon 20 insertion mutations: A systematic review and meta‑analysis. (PubMed, Oncol Lett) - "Subgroup analysis revealed the following ORRs: 0.731 (95% CI, 0.560-0.901; I2=0%) for YK-029A; 0.608 (95% CI, 0.511-0.705; I2=0%) for sunvozertinib; 0.602 (95% CI, 0.440-0.764; I2=80.2%) for furmonertinib; 0.602 (95% CI, 0.486-0.718; I2=84.5%) for befotertinib; 0.566 (95% CI, 0.236-0.896; I2=96.3%) for amivantamab; 0.444 (95% CI, 0.215-0.674; I2=0%) for BEBT-109; and 0.256 (95% CI, 0.178-0.334; I2=75.0%) for poziotinib. In conclusion, the emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile. However, further analysis is needed when more clinical data are released."

Journal • Retrospective data • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

Genetic biomarker study of sunvozertinib for clinical prognosis and prediction in NSCLC with EGFR exon 20 insertion mutation. (PubMed, Cell Rep Med) - "Acquired EGFR C797S is identified as a potential on-target resistance mutation to sunvozertinib. Finally, efforts are undertaken to investigate therapeutic approaches that aim to overcome the putative acquired resistance to sunvozertinib."

Biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A clinical review on third and fourth generation EGFR tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. (PubMed, Bioorg Med Chem) - "This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A highly potent and selective small molecule TY-4028 for the targeted therapy of non-small cell lung cancer with EGFR exon 20 or HER2 exon20 insertion mutations (AACR 2025) - "Furthermore, Antibody such as Amivantamab has difficulty penetrating the BBB, brain metastases presents a significant clinical challenge in lung cancer with EGFR exon20ins mutations...The data showed that the efficacy of TY-4028 was similar to that of Mobocertinib(TAK-788)and better than that of Sunvozertinib (DZD9008), whereas the tolerance of TY-4028 was better than that of Mobocertinib in CDX mouse models... TY-4028 is a novel, potent, and orally available inhibitor targeting EGFR and Her2 exon20ins mutations. It is a highly potent covalent inhibitor with rapid absorption and clearance, which contributes to the decreased toxicity of covalent drugs. Preclinical studies have shown a good PK profile and manageable toxicity with TY-4028."

EGFR exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

A phase II study of sunvozertinib combined with anlotinib in EGFR-TKIs resistant EGFRm advanced NSCLC patients (WUKONG9) (ELCC 2025) - P2 | "Sunvozertinib combined with Anlotinib is well tolerated and has demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who failed prior EGFR-TKIs therapies. Enrollment is ongoing and results will be updated at the meeting."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sunvozertinib: shining light on lung cancer's exon 20 fight. (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Will "Sun"-WUKONG, the monkey king, conquer EGFR exon 20 insertion mutation positive non-small cell lung cancer? (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Positive results from a Phase II study of sunvozertinib in combination with Anlotinib (PRNewswire) - P2 | N=45 | WUKONG-9 (NCT06182761) | "Sunvozertinib combined with anlotinib was well tolerated and demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who had failed prior EGFR-TKI therapies. As of December 25, 2024, the objective response rate (ORR) and the disease control rate (DCR) were 33.3% and 100%, respectively, in this heavily pre-treated patient population. Enrollment is ongoing and detailed results will be updated at the congress."

P2 data • Non Small Cell Lung Cancer

WU-KONG20: Perioperative Treatment of Sunvozertinib in Stage II-IIIB NSCLC (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: Tang-Du Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR Exon 20 S768I Mutant Lung Adenocarcinoma: A Case Report and Review of the Literature. (PubMed, Case Rep Oncol) - "After 1 month of chemotherapy with 860 mg of pemetrexed and 480 mg of carboplatin, and immunotherapy with 200 mg of sintilimab, good response to conventional chemotherapy, but a follow-up CT scan showed disease progression...Subsequently, chemotherapy with paclitaxel albumin 400 mg and treatment with pembrolizumab 200 mg were administered, followed by targeted treatment with oral afatinib (PFS: 12 months)...The results indicate that targeted therapy with afatinib and osimertinib for EGFR S7688I/V774M and TP53 mutations has better PFS than targeted therapy with furmonertinib and sunvozertinib. Simultaneously, the combination of platinum-based chemotherapy and immunotherapy may be a potential neoadjuvant therapy for NSCLC IVa stage patients."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • TP53

A real-world multicenter study of furmonertinib in EGFRex20ins mutant advanced NSCLC patients and related structural insights (ESMO-TAT 2025) - "Furthermore, based on the computational model findings, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), afatinib (-5.075; -44.64), mobocertinib (-7.213; -38.38) and sunvozertinib (-8.95; -57.03), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Advanced NSCLC patients with ex20ins mutation benefit from furmonertinib targeted therapy."

Clinical • EGFR exon 20 • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • JAK1

Assessing an Oral Bruton Tyrosine Kinase Inhibitor, DZD9008 in Patients Who Have Non-Hodgkin B-cell Lymphoma (WU-KONG3) (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Dizal Pharmaceuticals | N=120 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Real-world Study of Sunvozertinib Treatment in Advanced EGFR-Mutant NSCLC After EGFR-TKI Treatment Failure (clinicaltrials.gov) - P=N/A | N=55 | Not yet recruiting | Sponsor: Henan Cancer Hospital

New trial • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase II, Single-Arm Study Evaluating the Efficacy and Safety of Sunvozertinib in Combination with Glumetinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with MET Amplification or Overexpression Following EGFR-TKI Treatment Failure (WUKONG-37) (ChiCTR) - P4 | N=40 | Sponsor: Jiangsu Cancer Hospital; Jiangsu Cancer Hospital

New P4 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Efficacy and safety of Sunvozertinib for adjuvant treatment of stage IB-IIIB EGFR ex20ins mutated NSCLC after complete resection: a phase II, single-arm clinical study (ChiCTR) - P2 | N=25 | Sponsor: Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

U.S. FDA Granted Priority Review to Dizal’s Sunvozertinib New Drug Application (PRNewswire) - "Dizal...announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review to the company's New Drug Application (NDA) for sunvozertinib, an oral EGFR inhibitor for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins), as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy....The NDA submission is supported by efficacy and safety results from the multinational pivotal WU-KONG1 Part B study, evaluating sunvozertinib in relapsed or refractory NSCLC patients with EGFR exon20ins from Asia, Europe, North America, and South America."

EGFR exon 20 • Evidence highlight • FDA filing • Priority review • Non Small Cell Lung Cancer • EGFR

Sunvozertinib (DZD9008) in Pretreated Lung Cancer Patients with EGFR Exon20 Insertion Mutation (WU-KONG6) (clinicaltrials.gov) - P2 | N=104 | Active, not recruiting | Sponsor: Dizal Pharmaceuticals | Trial completion date: May 2024 ➔ Dec 2025

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

NUMER: Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations. (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Sun Yat-sen University | Not yet recruiting ➔ Recruiting

Biomarker • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

DZD9008 PK Study in Hepatic Impairment Subjects (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Dizal Pharmaceuticals | Recruiting ➔ Completed | Trial completion date: May 2024 ➔ Oct 2024

Trial completion • Trial completion date • Hepatology

Assessing the Effect of DZD9008 on the Pharmacokinetics of the Cocktail Probes Representative for CYP3A4, P-gp, BCRP and OATP1B1 in Patients with EGFR or HER2 Mutant Advanced Non-small Cell Lung Cancer (WU-KONG19) (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Dizal Pharmaceuticals | Recruiting ➔ Completed | Trial primary completion date: Aug 2024 ➔ May 2024

Metastases • Trial completion • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Dizal Announces Positive Pooled Data of Sunvozertinib in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Published in Lung Cancer (PRNewswire) - "Dizal...announced today the publication of a pooled analysis evaluating sunvozertinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)-resistant non-small cell lung cancer (NSCLC) in the official journal of the European Society for Medical Oncology (ESMO) Lung Cancer....The best objective response rate (ORR) was 27.5 %, and disease control rate (DCR) was 60 %. The median duration of response (mDoR) and progression free survival (mPFS) were 6.5 months and 6 months, respectively. Greater ORR of 55.6% was seen in patients with EGFR sensitizing and T790M double mutations (78% had received third-generation EGFR-TKI treatment in prior lines of therapy). Sunvozertinib was well-tolerated, and the safety profile was consistent with previous reports."

Retrospective data • Non Small Cell Lung Cancer