Drug Trials Snapshots: ZEGFROVY

ZEGFROVY (sunvozertinib) tablets, for oral use zeg-FROH’-vee Dizal (Jiangsu) Pharmaceutical Co., Ltd. Approval date: July 2, 2025 DRUG TRIALS SNAPSHOT SUMMARY: What is the drug for? ZEGFROVY is a kinase inhibitor and is available by prescription. ZEGFROVY is used as a single agent for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after a platinum-based chemotherapy. How is this drug used? ZEGFROVY is a tablet taken with food by mouth once daily. Who participated in the clinical trials? The FDA approved ZEGFROVY based on evidence from one clinical trial (WU-KONG1B / NCT03974022) in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on platinum-based chemotherapy and received ZEGFROVY 200 mg once daily with food. WU-KONG1B enrolled 202 patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who had received previous platinum-based chemotherapy. The trial was conducted at 89 sites the United States, Argentina, Australia, Canada, China, Chile, France, Italy, Malaysia, South Korean, Spain, and Taiwan. The number of patients representing the efficacy findings differs from the number of patients representing safety due to different pools of study participants analyzed for efficacy and safety. How were the trials designed? WU-KONG1B was a multinational, open-label, dose randomization trial in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with disease progression on or after platinum-based chemotherapy. Patients were randomized (1:1) to either receive ZEGROVY 200 mg orally once daily with food or ZEGFROVY at an unapproved dose once daily with food. Patients were treated with ZEGFROVY until disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or unacceptable toxicity. Randomization was stratified by prior therapies (<3 versus 3) and baseline brain metastasis (yes versus no). Tumor assessments were conducted every six weeks. The major efficacy outcome measure was confirmed blinded independent review committee (BIRC) assessed overall response rate (ORR) according to RECIST v1.1. Additional efficacy outcome measure was BIRC-assessed duration of response (DOR). A total of 192 patients were enrolled and randomized to ZEGFROVY 200 mg (n=85) or ZEGFROVY at an unapproved dose (n=89). An additional 18 patients were not randomized and received ZEGFROVY at an unapproved dose (N=107 total patients received ZEGFROVY at an unapproved dose). The efficacy population characteristics were: median age of 61 years (range: 35 to 88); 43% age 65 or older; 67% female; 65% Asian, 33% White; and 61% with Eastern Cooperative Oncology Group (ECOG) performance status of 1. A total of 96% of patients had metastatic disease at study entry and 94% had adenocarcinoma histology. All 85 patients in the efficacy population had EGFR exon 20 insertion mutations in tumor based prospective local or central laboratory testing. The ORR was 46% (95% CI: 35, 57) and DOR was 11.1 months (95% CI: 8.2, not evaluable). DEMOGRAPHICS SNAPSHOT Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of ZEGFROVY. Figure 1. Baseline Demographics by Sex, Efficacy Population Source: Adapted from FDA Multidisciplinary Review Figure 2 summarizes how many patients by sex were enrolled in the clinical trial used to evaluate the side effects of ZEGFROVY. Figure 2. Baseline Demographics by Sex, Safety Population Source: Adapted from Multidisciplinary Review Figure 3 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of ZEGFROVY. Figure 3. Baseline Demographics by Race, Efficacy Population Source: Adapted from Multidisciplinary Review Figure 4 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the side effects of ZEGFROVY. Figure 4. Baseline Demographics by Race, Safety Population Source: Adapted from FDA Multidisciplinary Review Figure 5 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of ZEGFROVY. Figure 5. Baseline Demographics by Age, Efficacy Population Source: Adapted from FDA Multidisciplinary Review Figure 6 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the side effects of ZEGFROVY. Figure 6. Baseline Demographics by Age, Safety Population Source: Adapted from FDA Multidisciplinary Review Figure 7 how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of ZEGFROVY. Figure 7. Baseline Demographics by Ethnicity, Efficacy Population Source: Adapted from FDA Multidisciplinary Review Figure 8 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the side effects of ZEGFROVY. Figure 8. Baseline Demographics by Ethnicity, Safety Population Source: Adapted from FDA Multidisciplinary Review What are the benefits of this drug? ZEGFROVY was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trial(s) to confirm that the drug works well. In WU-KONG1B, 46% of patients with EGFR exon 20 insertion mutations treated with ZEGFROVY in the clinical study experienced complete or partial shrinkage of their tumors. Shrinkage lasted at least six months for 72% of these patients. Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups? Sex: ZEGFROVY worked similarly in males and females. Race: The observed effect of ZEGFROVY was larger for Asian than White patients. Because of limited data, this difference may be due to chance. Age: The observed effect of ZEGFROVY was larger for patients 65 years of age and older than younger patients. Because of limited data, this difference may be due to chance. What are the possible side effects? ZEGFROVY may cause serious and potentially deadly side effects, including inflammation of the lungs (pneumonitis), stomach and intestinal (gastrointestinal) problems, skin problems, eye problems, and harm to an unborn baby. The most common side effects of ZEGFROVY are diarrhea, rash, decreased appetite, mouth sores, feeling very tired, nausea, infected skin around the nail, vomiting, constipation, muscle or joint pain, itchy skin, dry skin, urinary tract infection, stomach-area pain, and decreased weight. Were there any differences in side effects among sex, race and age? Sex: The occurrence of side effects was similar in males and females. Race: The occurrence of side effects was similar in Asian and White patients, except that occurrence of Grade ≥3 treatment-emergent adverse events was higher in patients of White or other races. Because of limited data, this difference may be due to chance. Age: The occurrence of side effects was similar in patients younger and older than 65 years of age. GLOSSARY CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. EFFICACY: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effectsof the active drug or treatment are compared to the effects of the placebo. SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups. PRESCRIBING INFORMATION