About three years after a phase 3 flop led Takeda to withdraw its Exkivity from the EGFR exon 20 lung cancer market, Dizal Pharma has data showing its small molecule drug may have what it takes to challenge Johnson & Johnson’s antibody in the first-line setting.
The Chinese company’s Zegfrovy, or sunvozertinib, significantly reduced the risk of disease progression or death by 35% compared with platinum-based chemotherapy as first-line treatment in advanced non-small cell lung cancer 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, median progression-free survival for patients who received Zegfrovy reached 10.3 months, versus 7.5 months for the chemo control group, by blinded independent central review.
Data on overall survival were immature as only about 38.9% of patients in the study had passed away, according to an article published simultaneously in The New England Journal of Medicine. At a median follow-up for overall survival of 26 months between the two groups, 62 patients (38%) in the sunvozertinib group and 64 patients (39.8%) in the chemotherapy group had died.
The two arms’ overall survival curves crossed in the middle of the trial, which the study’s investigators attributed to “a small number of early deaths that were unrelated to the trial treatment and were associated with disease progression or underlying disease with heavy tumor burden.” Further complicating the interpretation of the OS results, 90.2% of patients in the chemotherapy arm crossed over to receive Zegfrovy upon disease progression.
To demonstrate the power of crossover to Zegfrovy, Dizal CEO Xiaolin Zhang, Ph.D., noted that the median OS for the control arm is nearing 29 months, while historically, patients who took chemotherapy only reached a median OS of 17 to 25 months, including in J&J’s Papillon trial.
Zhang also pointed to PFS2, which measures the time from randomization to progression on the next-line therapy, to prove that Zegfrovy first-line treatment did not negatively impact second-line treatment. Here, Zegfrovy improved PFS2 by 30%, with a median of 21.7 months, as compared to 15.5 months for chemotherapy.
Assuming the current data can be interpreted as no potential detriment to patient survival, a statistically significant PFS win will likely be enough for Zegfrovy to secure an FDA approval. The drug already received the FDA’s accelerated approval last year as a second-line therapy.
It’s been more than two years since J&J’s bispecific antibody Rybrevant, used in tandem with the chemo combo of carboplatin and pemetrexed, was cleared by the FDA in first-line EGFR exon 20 NSCLC.
Zegfrovy’s PFS efficacy results appeared slightly weaker than those from the Rybrevant cocktail by cross-trial comparison.
In the phase 3 Papillon trial, Rybrevant plus chemo improved PFS by 60% versus chemo alone in this setting. The median PFS was 11.4 months and 6.7 months in the respective arms.
The J&J regimen’s overall response rate (ORR) reached 67%, with the response lasting a median of 10.1 months, whereas chemotherapy’s 36% ORR came with 5.6 months in median duration of response (DOR).
In Wu-Kong28, ORR was 58.9% for Zegfrovy and 31.1% for chemo, and DOR was 11.2 months and 7.1 months, respectively.
Previously, Takeda’s Exclaim-2 trial found similar efficacy between Exkivity and platinum-based chemo with the same median PFS, 9.6 months, in each treatment arm at an interim analysis. Even though chemo appeared to have performed better than expected in that study compared with Papillon and Wu-Kong28, its 32% ORR was the weakest of the three regimens and was not materially different from 30% with chemo within the study.
Despite its seemingly weaker PFS, Zegfrovy achieved its efficacy all by itself as a once-daily oral drug, whereas Rybrevant is an injection or infusion that must be combined with toxic chemo and administered by a healthcare professional.
During his presentation of the Wu-Kong28 results, John Heymach, M.D., chair of thoracic/head and neck medical oncology at MD Anderson Cancer Center, said Zegfrovy offers “the advantage of a single oral agent administration” but also said the J&J regimen “remains an option there for patients.”
During an interview with Fierce at ASCO 2024, Dizal's CEO Zhang argued that trying to maximize efficacy with chemo up front in first-line EGFR exon 20 NSCLC may not be a desirable strategy, as adding chemo hurts patients’ quality of life.
Based on Wu-Kong28, Dizal announced Thursday that Chinese regulators have accepted the company’s first-line application under priority review. As for the U.S., Zhang said the company files globally.
For the global market, Dizal is in “late-stage discussion with several partners,” Zhang said. The company hasn’t been able to close a deal because, after Exkivity’s flop, potential partners would rather wait for the Wu-Kong28 readout, he explained.
Speaking of the characteristics of an ideal partner, Zhang said Dizal is looking for a partner with global reach that marks a strategic fit portfolio-wise, and who has experience marketing a targeted therapy.
To move Zegfrovy into even earlier treatment, Dizal 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 is launching the Wu-Kong18 global trial in the same setting. Both studies will also enroll patients with P-loop and αC-helix compression mutations, another subset of uncommon EGFR mutations.
Meanwhile, the priority for Rybrevant these days is its high-stakes battle with AstraZeneca’s blockbuster tyrosine kinase inhibitor Tagrisso in the much larger market of traditional EGFR-mutated NSCLC. There, Dizal is exploring Zegfrovy’s potential combination with the firm’s fourth-generation EGFR TKI—dubbed DZD6008— in an early-stage, proof-of-concept study coded Tian-Shan8.
When asked if DZD6008 and Zegfrovy could become a package deal for collaboration, Zhang said, “it depends on the terms.”
As Dizal’s R&D programs expand and its commercial portfolio deepens, the Shanghai-listed company in January filed for double listing on the Hong Kong Stock Exchange.
Editor's Note: The story was updated 12:20 a.m. ET, June 2, with additional comments from Dizal CEO Xiaolin Zhang, Ph.D., and Wu-Kong28's presenter John Heymach, M.D.