Editor’s note: This article will be updated after the study is published Friday afternoon. Please check back later.
Nearly three years after Takeda pulled Exkivity from the EGFR exon 20 lung cancer market due to Phase 3 failures, Disal Pharma has obtained data showing its small molecule drug may have what it takes to counter Johnson & Johnson’s antibodies in the first-line setting.
The Chinese company’s Zegfrowi (sumvozertinib) significantly reduced the risk of disease progression or death by 35% compared to platinum-based chemotherapy as a first-line treatment for advanced non-small cell lung patients with EGFR exon 20 insertion mutations, according to an abstract released ahead of Dizal’s presentation Friday at the American Society of Clinical Oncology 2026 Annual Meeting.
In the global phase 3 Wu-Kong28 trial, blinded independent central review found that patients treated with Zegfrovy had a median progression-free survival of 10.3 months, compared with 7.5 months in the chemotherapy control group.
Only about 38.9% of patients in the study died, and data on overall survival were immature, according to a paper published simultaneously in the New England Journal of Medicine. Median overall survival follow-up between the two groups was 26 months, with 62 (38%) deaths in the sumbozertinib group and 64 (39.8%) deaths in the chemotherapy group.
The overall survival curves for both groups crossed midway through the trial, which the study’s researchers attributed to “a small number of early deaths unrelated to study treatment and related to disease progression and underlying disease with heavy tumor burden.” Further complicating the interpretation of the OS results, 90.2% of patients in the chemotherapy arm switched to Zegflovy as their disease progressed.
Wu-Kong28 interim overall survival (maturity 38.9%) (Caicun Zhou, et al./NEJM)
Assuming the current data can be interpreted as having no potential negative impact on patient survival, a statistically significant PFS win would likely be sufficient for Zegfrovy to gain FDA approval. The drug already received early FDA approval as a second-line therapy last year.
More than two years have passed since J&J’s bispecific antibody Rybrevat, used in combination with carboplatin and pemetrexed chemotherapy, was approved by the FDA for first-line EGFR exon 20 NSCLC.
Based on cross-study comparisons, the efficacy results for Zegfrovy appeared to be slightly weaker than those for the Rybrevant cocktail.
In the phase 3 Papillon trial, Rybrevant plus chemotherapy improved PFS by 60% compared to chemotherapy alone in this setting. Median PFS was 11.4 months and 6.7 months in each arm.
J&J therapy achieved an overall response rate (ORR) of 67% with a median duration of response of 10.1 months, compared to chemotherapy’s ORR of 36% and median duration of response (DOR) of 5.6 months.
In Wu-Kong28, ORR was 58.9% with Zegfrovy and 31.1% with chemotherapy, and DOR was 11.2 and 7.1 months, respectively.
Previously, Takeda’s Exclaim-2 trial showed similar efficacy between Exkivity and platinum-based chemotherapy in each treatment arm at an interim analysis, with the same median PFS of 9.6 months. Although chemotherapy appeared to perform better than expected in this study compared with Papillon and Wu-Kong28, its 32% ORR was the weakest of the three regimens and was not significantly different from the 30% with chemotherapy within the study.
Zegfrovy achieved its effectiveness on its own as a once-daily oral medication despite seemingly weak PFS, whereas Rybrevant is an injection or infusion and must be administered by a medical professional in combination with toxic chemotherapy.
In an interview with Fierce at ASCO 2024, Dizal CEO Dr. Xiaolin Zhang argued that for first-line EGFR exon 20 NSCLC, trying to maximize efficacy with upfront chemotherapy may not be a desirable strategy as the addition of chemotherapy impairs patients’ quality of life.
Based on Wu-Kong28, Disal announced on Thursday that Chinese regulators have accepted the company’s initial application under priority review.
To move Zegfrovy into even earlier stages of treatment, Dr. Disal is evaluating the targeted therapy as an adjuvant therapy for stage 1b to 3a EGFR exon 20 NSCLC in the Wu-Kong16 trial in China, and plans to initiate the Wu-Kong18 global trial in the same setting. Both studies will also enroll patients with P-loop and αC-helix compaction mutations, another subset of rare EGFR mutations.
Meanwhile, LiveLevant’s priority these days is a high-stakes battle with AstraZeneca’s blockbuster tyrosine kinase inhibitor Tagrisso in the much larger market of traditional EGFR-mutated NSCLC. So Dizal is exploring the potential combination of Zegflovy with the company’s fourth-generation EGFR TKI (called DZD6008) in an early proof-of-concept study coded Tian-Shan8.
As DiZal’s research and development program expands and its commercial portfolio deepens, the Shanghai-listed company applied for dual listing on the Hong Kong Stock Exchange in January.
