Sunvozertinib Earns FDA Breakthrough Therapy Designation in EGFR+ NSCLC

Supporting data for the breakthrough therapy designation came from the international phase 1/2 WU-KONG1 trial (NCT03974022). Investigators previously presented findings from a pooled analysis of the WU-KONG1 trial and the WU-KONG15 trial (NCT05559645) at the 2023 European Society for Medical Oncology Congress (ESMO).

The FDA has granted breakthrough therapy designation to sunvozertinib (DZD9008) as a frontline treatment for patients with locally advanced or metastatic non–small cell lung (NSCLC) with EGFR exon 20 insertion mutations, according to a press release from developers Dizal.¹

Developers hypothesized that the molecular structure of sunvozertinib allows it to overcome difficulties associated with targeting EGFR exon 20 insertion mutations. It is believed that the agent’s design may enable improvements in efficacy, safety, and ease of administration among the aforementioned population.

“We are delighted with the FDA's decision granting the breakthrough therapy designation to sunvozertinib for first-line treatment, coming on the heels of earlier [breakthrough therapy designation] approval in later lines of therapy — a clear indication of sunvozertinib’s transformative potential in the treatment of patients with EGFR exon 20 insertion NSCLC,” Xiaolin Zhang, PhD, chief executive officer at Dizal, said in the press release.¹ “This new [breakthrough therapy designation] will enable us to work more closely with the FDA and accelerate its clinical development and regulatory submission.”

Supporting data for the breakthrough therapy designation came from the international phase 1/2 WU-KONG1 trial (NCT03974022). Investigators previously presented findings from a pooled analysis of the WU-KONG1 trial and the WU-KONG15 trial (NCT05559645) at the 2023 European Society for Medical Oncology Congress (ESMO).

Of 28 evaluable patients with NSCLC harboring EGFR exon 20 insertion mutations, including 19 who received sunvozertinib at 200 mg once daily and 9 who received the agent at 300 mg once daily, the best objective response rate (ORR) was 71.4%.² The median duration of response (DOR) was not reached at the time of the analysis.

Common treatment-emergent adverse effects (TEAEs) in the trial included diarrhea, creatine phosphokinase increases, and skin rash. According to the investigators, most toxicities were grade 1/2 and clinically manageable.

“…The latest research results from the pooled analysis of sunvozertinib provide further evidence to this therapeutic area and showcase its significant tumor response and clinically meaningful outcomes as a potential 'best-in-class' treatment,” Zhang said in a press release on these findings.³

In the WU-KONG1 trial, investigators assessed treatment with sunvozertinib at escalating doses in part A and as part of a dose-extension phase in part B.⁴

The trial’s primary end points included safety and tolerability in part A and ORR based on RECIST v1.1 criteria in part B. The plasma concentration of sunvozertinib was a secondary end point.

Patients 18 years and older with histologically or cytologically confirmed locally advanced or metastatic NSCLC harboring EGFR or HER2 mutations were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, a minimum life expectancy of 12 weeks, measurable disease per RECIST v1.1 guidelines, adequate organ function, and 1 to 3 prior lines of systemic therapy for metastatic or locally advanced disease.

Those who had prior treatment with EGFR or HER2 antibodies, major surgery, or immunotherapy within 4 weeks of entry were ineligible for enrollment on the trial. Patients were also unable to enroll if they had any cytotoxic chemotherapy within 2 weeks of screening, spinal cord compression or leptomeningeal metastasis, prior interstitial lung disease, refractory nausea and vomiting that precluded adequate absorption of study treatment, or any unresolved toxicities from previous therapy greater than grade 1.

According to the press release, sunvozertinib previously received breakthrough therapy designation from the China Center for Drug Evaluation as a treatment for those with relapsed/refractory disease in 2023; the agent was subsequently approved for this indication in China.¹

References

1. FDA grants breakthrough therapy designation to sunvozertinib for the first-line treatment of patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations. News release. Dizal. April 7, 2024. Accessed April 9, 2024. https://tinyurl.com/yjy8jhm4
2. Yang JCH, Wang M, Chiu CH, et al. Sunvozertinib as first-line treatment in NSCLC patients with EGFR Exon20 insertion mutations. Ann Oncol. 2023;34(suppl 2):S765. doi:10.1016/j.annonc.2023.09.2358
3. Sunvozertinib demonstrates best-in-class potential as a first-line treatment for EGFR exon 20 insertion mutation-positive non-small cell lung cancer patients. News release. Dizal. October 23, 2023. Accessed April 9, 2024. https://tinyurl.com/4ffdcvyn
4. Assessing an oral EGFR inhibitor, DZD9008 in patients who have advanced non-small cell lung cancer with EGFR or HER2 mutation (WU-KONG1). ClinicalTrials.gov. Accessed April 9, 2024. https://tinyurl.com/mpm3hf36