New RET Inhibitor Lunbotinib in Lung Cancer: Response Exceeding %80

High Response Rate, Long PFS and Strong Activity in Brain Metastases

Treatment in RET Fusion-Positive NSCLC Is No Longer Measured Solely by the Initial Response Rate

RET fusions occur in approximately %1–2 of NSCLC cases. Although this proportion may appear small, every targetable driver alteration has major clinical significance in advanced lung cancer. When the right molecular target is identified, treatment can become much more selective and effective than conventional chemotherapy or immunotherapy approaches.

However, in RET-targeted therapy, asking only whether the tumor is shrinking is no longer enough. The key questions have become more complex: How durable is the response? Is it effective in brain metastases? Is the treatment discontinuation rate low? What happens when resistance develops? Can dynamic biomarkers such as ctDNA indicate an early response? The lunbotinib data provide promising answers to several of these questions at once.

Two Main Patient Groups Were Evaluated With Lunbotinib 90 mg Once Daily

In the pivotal phase 2 study presented at ASCO 2026, lunbotinib was administered at a dose of 90 mg once daily. The analysis included two main patient groups: treatment-naive patients who had not previously received systemic therapy, and previously treated patients who had received platinum-based chemotherapy and immunotherapy.

The data cutoff date was 29 October 2025. Median follow-up in the previously treated group was 22,6 monthsand in the treatment-naive group was 20,7 months. This follow-up period provides meaningful observation for assessing not only early response rates, but also response durability and the PFS signal.

Response Rate Exceeds %80 in Both Groups

According to independent assessment, the objective response rate in previously treated patients was reported as %87,1and in treatment-naive patients as %81,3 . This result is particularly striking because the response rate was also very high in previously treated patients, who are generally considered more resistant.

Median PFS in the previously treated group was 27,5 months. In the treatment-naive group, median PFS had not yet been reached. The PFS rates at 24 months in the previously treated group were reported as %52,1and in the treatment-naive group as %59,9 . Median OS had not yet been reached in either group.

Strong Responses Also Seen in Patients With Brain Metastases at Baseline

Central nervous system metastases are a clinically important problem in RET fusion-positive NSCLC. The ability of a new RET inhibitor to demonstrate efficacy in brain metastases as well as systemic disease is therefore critical to treatment selection.

The data presented at ASCO 2026 also reported strong activity with lunbotinib in patients with brain metastases at baseline. The response rate in previously treated patients with brain metastases was reported as %82,6and in treatment-naive patients as %75,0 . Both cohorts included patients who achieved an intracranial complete response.

Could ctDNA Clearance at Week 8 Be an Early Signal for PFS?

The ctDNA analysis was another notable topic in the ASCO presentation. PFS appeared longer in patients who were ctDNA-negative at baseline, and markedly better PFS was also observed in patients who were ctDNA-positive at baseline but had ctDNA clearance at week 8. The presentation reported median PFS in patients with ctDNA clearance at week 8 as 27,5 monthsand in those without clearance as 7,3 months. These were the reported durations.

Manageable Safety Profile and Low Rate of Permanent Treatment Discontinuation

Lunbotinib generally showed a manageable safety profile. Most treatment-related adverse events were grade 1–2. The rate of grade 3 or higher treatment-related adverse events was reported as %40,5and the rate of permanent treatment discontinuation due to treatment-related adverse events as %1,2 . No treatment-related deaths occurred.

The presentation slides emphasized that hematologic toxicities were of low severity, rates of interstitial lung disease and hypertension remained low, and no new safety signals were observed. This is important because RET inhibitors are targeted therapies that can be used over long periods, and treatment continuity often depends on adverse event management.

Competition Among a New Generation of RET-Targeted Therapies Begins

The first major breakthrough in RET fusion-positive NSCLC came with the development of selective RET inhibitors such as selpercatinib and pralsetinib. These drugs showed that they could provide higher response rates and longer disease control than chemotherapy. More recently, randomized studies such as LIBRETTO-431 for selpercatinib and AcceleRET-Lung for pralsetinib have strengthened the first-line use of RET-targeted therapies.

Lunbotinib enters this field as a next-generation candidate. The available data are not from a randomized phase 3 study; however, ORR above %80 in both treatment-naive and previously treated groups, a long PFS signal, activity in CNS metastases and a low rate of permanent discontinuation make the drug a strong candidate option that deserves close attention in the RET field.

Molecular Testing, Brain Assessment and Dynamic Monitoring Become Even More Important

The lunbotinib data show that targeted treatment options for RET fusion-positive NSCLC are expanding rapidly. However, using these treatments requires detection of the RET fusion at diagnosis. Starting treatment in advanced nonsquamous NSCLC without comprehensive NGS or a reliable fusion test may therefore delay the opportunity for targeted therapy.

Assessment for brain metastases should also be part of treatment selection. Central nervous system involvement can occur in RET-positive patients, and a new RET inhibitor's CNS activity may provide an important advantage in the treatment algorithm. In addition, ctDNA dynamics may be used more extensively in the future to detect treatment response early and monitor the development of resistance.

Treatment Selection in RET-Positive Lung Cancer Is Becoming More Refined

How Will Lunbotinib's Actual Role Be Determined?

The lunbotinib data are strong, but the current evidence is not at the level of a randomized phase 3 comparison. The drug's actual position relative to selpercatinib, pralsetinib or standard treatment must therefore be clarified with more mature and comparative data.

Lunbotinib Stands Out as a Strong Next-Generation Candidate in RET Fusion-Positive Lung Cancer

The pivotal phase 2 study presented at ASCO 2026 showed that lunbotinib fumarate / A400 / EP0031 can provide high response rates and durable disease control in both treatment-naive and previously treated patients with advanced RET fusion-positive NSCLC. The objective response rate was %87,1 in previously treated patients and %81,3 in treatment-naive patients. Median PFS in the previously treated group was reported as 27,5 months; median PFS in the treatment-naive group had not yet been reached.

The reporting of high response rates and intracranial complete responses in patients with brain metastases at baseline also suggests that the drug has important potential for CNS efficacy. In addition, the association between ctDNA clearance at week 8 and longer PFS opens the way for biomarker studies that could allow us to assess treatment response earlier and more dynamically in the future.

On safety, although the rate of grade 3 or higher treatment-related adverse events was %40,5, the permanent treatment discontinuation rate of %1,2 and treatment-related death rate of %0 indicate a manageable profile. Nevertheless, without a randomized comparison and longer follow-up, lunbotinib's precise role among existing RET inhibitors has not been established. The current message is that targeted therapies for RET fusion-positive NSCLC are moving toward an era of greater selectivity, greater focus on the brain and greater support from dynamic biomarkers.