ASCO 2026: Sunvozertinib and Selpercatinib Move the Needle in Molecularly Defined Lung Cancer

ASCO 2026: Sunvozertinib and Selpercatinib Move the Needle in Molecularly Defined Lung Cancer

At a Glance

• WU-KONG28 is a phase 3 trial of sunvozertinib vs. platinum-based chemotherapy in untreated advanced NSCLC with EGFR exon 20 insertion mutations; sunvozertinib extended median PFS to 10.3 vs. 7.5 months
• Sunvozertinib offers a chemotherapy-free frontline option for a historically difficult-to-treat NSCLC subgroup
• LIBRETTO-432 is a phase 3 trial of adjuvant selpercatinib vs. placebo in stage IB-IIIA RET fusion–positive NSCLC; median EFS was not reached with selpercatinib vs. 31.8 months with placebo
• Both trials underscore the importance of comprehensive molecular testing in all NSCLC patients

Introduction

At the 2026 ASCO Annual Meeting, some of the most consequential lung cancer data centered on molecularly defined subgroups, reinforcing the field's ongoing shift toward biomarker-driven treatment. Apar Kishor P. Ganti, MD, thoracic oncologist, identified two trials as the meeting's most influential lung cancer updates: WU-KONG28, examining sunvozertinib in EGFR exon 20 insertion–mutant NSCLC, and LIBRETTO-432, examining adjuvant selpercatinib in RET fusion–positive NSCLC. We asked Dr. Ganti for his perspective on both trials and their implications for clinical practice.

WU-KONG28: A Chemotherapy-Free Option for Exon 20 Insertion NSCLC

“WU-KONG28 (NCT05668988) was a global randomized phase 3 study in patients with untreated advanced NSCLC and an exon 20ins mutation,” Ganti explains. “This trial randomized 324 patients to either sunvozertinib (n=163) or platinum-based chemotherapy (n=161). The primary endpoint was progression free survival (PFS) assessed by blinded independent central review using the RECIST 1.1 criteria.”

The results favored sunvozertinib. “The study met its primary endpoint, with the median PFS being significantly longer with sunvozertinib (10.3 vs 7.5 months; HR: 0.65, 95% CI: 0.50, 0.85, p=0.0008),” Ganti says. “In addition, sunvozertinib showed higher confirmed response rate (58.9% vs 31.1%) and these patients had a longer median duration of response (11.2 vs 7.1 months).”

In terms of toxicity, “Sunvozertinib was reasonably well tolerated with 7.4% patients discontinuing the drug due to side effects.”

It is important to note that in current practice, the majority of patients are not using chemotherapy alone. “The current standard of care of these patients is amivantamab + chemotherapy, which was not the control arm in this study,” Ganti says. “Nonetheless, this represents a chemotherapy-free option for the management of these patients.”

LIBRETTO-432: Adjuvant Selpercatinib Sets a New Standard in RET-Positive Early-Stage NSCLC

“LIBRETTO-432 was a randomized, placebo controlled, double-blind, phase 3 trial for patients with stage IB-IIIA RET-positive NSCLC, who had completed definitive local regional treatment,” Ganti says of his second pick for important lung research. “The study randomized 151 patients to selpercatinib (n=75) or placebo (n=76) for up to 3 years.”

Selpercatinib outperformed the placebo. “The primary endpoint of the study was EFS in patients with stage II-IIIA. The median EFS was significantly better with selpercatinib (NR vs. 31.8 m; HR 0.172; 95% CI, 0.058, 0.509; p=0.0003). The 2-year EFS rate was also higher with selpercatinib (91.5% vs. 61.1%).” And in terms of toxicity, “there were no new safety signals seen with selpercatinib.”

“Although RET positive NSCLC is not very common and represents 1-2% of the NSCLC population, adjuvant selpercatinib is the new standard for RET positive patients with early-stage non-small cell lung cancer following definitive local therapy,” Ganti concludes. “These results also demonstrate the importance of obtaining molecular testing in all patients with NSCLC.”

About the Reviewer

Apar Kishor P. Ganti, MD, is a thoracic oncologist at the University of Nebraska Medical Center in Omaha, Nebraska.