SOHO-02 Trial Will Confirm Sevabertinib’s Frontline NSCLC Benefit

The FDA granted accelerated approval to frontline sevabertinib (Hyrnuo) based on the single-arm phase 1/2 SOHO-01 trial (NCT05099172).¹ Among 69 treatment-naive patients in cohort F, sevabertinib produced an objective response rate of 75% (95% CI, 64%-85%). The ongoing, confirmatory phase 3 SOHO-02 trial (NCT06452277) is randomly assigning patients with treatment-naive, HER2 mutation-positive NSCLC to receive sevabertinib or chemoimmunotherapy to confirm this benefit.²

Xiuning Le, MD, PhD, an associate professor in the department of Thoracic/Head and Neck Medical Oncology at UT MD Anderson Cancer Center, spoke with CancerNetwork^® about what confirmatory data are needed to convert the accelerated approval for sevabertinib to a full approval.

Transcript:

CancerNetwork: Because this accelerated approval was based on the response rate and duration of response, what confirmatory data will be needed to convert this to full approval, and how confident are you that it will get there?

I’ll break your question down into a couple [of parts]. The accelerated approval was based on our SOHO-01 cohort F study, where we enrolled [patients with] treatment-naive HER2-mutant metastatic lung cancer.¹ We saw a very impressive response, with a response rate of 75% and a [median] progression-free survival of 13.5 months—very good efficacy.Therefore, the FDA rendered the accelerated approval based on that single-arm study.

The confirmatory study is actually ongoing—that’s called SOHO-02.² In that study, we’re enrolling [patients with] treatment-naive HER2 mutation-positive non–small cell lung cancer and randomly [assigning] them to sevabertinib vs chemoimmunotherapy because, at the time SOHO-02 was activated, chemoimmunotherapy was the standard of care. We’re looking forward to reading out that randomized study to see the PFS and response rate. We’re very encouraged that SOHO-02 will potentially also be positive in the final readout.

That data is supported by a recent report from DESTINY-Lung04 [NCT050487970], which compared trastuzumab deruxtecan [Enhertu] in the frontline setting vs chemoimmunotherapy.³ In the chemoimmunotherapy control arm, the median PFS was approximately [8.3] months. You can imagine that in SOHO-02, if sevabertinib maintains its efficacy in the 13-to-14-month range, that’s clearly going to be superior to chemoimmunotherapy. We’re very confident that once the study reads out, sevabertinib will maintain to be in the frontline setting.

References

1. FDA grants accelerated approval to sevabertinib for locally advanced or metastatic non-squamous non-small cell lung cancer. News release. FDA. September 9, 2026. Accessed September 21, 2026. https://tinyurl.com/mwsay6jf
2. A study to learn more about how well sevabertinib works and how safe it is compared with standard treatment, in participants who have advanced non-small cell lung cancer (NSCLC) with mutations of the human epidermal growth factor receptor 2 (HER2) (SOHO-02). ClinicalTrials.gov. Updated September 10, 2026. Accessed September 21, 2026. https://tinyurl.com/2k32z6wu
3. Rotow J, Okamoto I, Goto K, et al. First-line trastuzumab deruxtecan (T-DXd) in patients with metastatic HER2-mutant NSCLC: DESTINY-Lung04 primary results. Presented at the IASLC 2026 World Conference on Lung Cancer (WCLC); September 12-15, 2026; Seoul, South Korea. PL03.08