RET Highlights Presented at the 2026 American Society of Clinical Oncology (ASCO)

Here we summarize the RET cancer studies that were presented at the meeting this year.

Selpercatinib Shows Strong Results in Early-Stage RET+ Lung Cancer

Eli Lilly announced positive phase III LIBRETTO-432 results for Retevmo (selpercatinib) in early-stage RET fusion-positive NSCLC. Results were presented at ASCO 2026 on Sunday 31st May and published in NEJM. The study shown a reduction of the risk of recurrence or death by 83% vs. placebo and significantly improving event-free survival.

Some key findings from the study:

• A total of 151 patients were assigned to receive selpercatinib (75 patients) or placebo (76 patients).
• Median follow-up was 24 months and 27 months in the respective groups.
• Among 109 patients with stage II or IIIA disease, the event-free survival was 92% with selpercatinib and 61% with placebo.
• Among the 151 patients with stage IB, II, or IIIA NSCLC, the event-free survival at 2 years was 94% with selpercatinib and 70% with placebo.
• The most common adverse events during the treatment period were increased levels of alanine aminotransferase and aspartate aminotransferase. Three deaths occurred, all in the placebo group, owing to disease progression.

Conclusions: Among patients with stage II or IIIA RET fusion–positive NSCLC, event-free survival was significantly longer with adjuvant selpercatinib than with placebo. 

Eli Lilly plans to submit the results to global health authorities.

More info here: https://investor.lilly.com/news-releases/news-release-details/lillys-retevmo-selpercatinib-demonstrated-83-reduction-risk

Find the publication here: https://www.nejm.org/doi/full/10.1056/NEJMoa2602628?utm_source=conf&utm_medium=qr&utm_campaign=ASCO2026

Lunbotinib Shows Promising Results in RET Fusion-Positive Lung Cancer

New data presented at ASCO highlighted the efficacy and safety of lunbotinib (A400/EP0031), a next-generation selective RET inhibitor, in patients with RET fusion-positive advanced non-small cell lung cancer (NSCLC).

The results come from a pivotal Phase 2 study (NCT05265091) conducted in China by Kelun-Biotech, which is co-developing lunbotinib (EP0031/A400) with Ellipses Pharma (in the US, EU, UK and UAE). The study evaluated the treatment in both previously treated (SRI naïve, but prior chemotherapy +/- immunotherapy) and treatment-naïve patients with locally advanced or metastatic RET fusion-positive NSCLC.

Presented by Dr. Qing Zhou, the study demonstrated encouraging and durable clinical activity across multiple patient groups.

Patient population:

92 patients were enrolled in the treatment-naïve cohort and 71 patients in the previously treated cohort (prior chemotherapy or immunotherapy; no prior RET inhibitors). The study was conducted exclusively in an Asian patient population.

Efficacy:

Treatment-Naïve Patients:

• Objective Response Rate (ORR): 81.3%
• Median Progression-Free Survival (PFS): Not yet reached
• 24-month PFS rate: 59.9%

Previously Treated Patients:

• Objective Response Rate (ORR): 87.1%
• Median Progression-Free Survival (PFS): 27.5 months

Brain Metastases

• Lunbotinib demonstrated robust efficacy in patients with baseline brain metastases, an important consideration for many people living with RET-positive lung cancer.

Safety

• Lunbotinib showed a manageable safety and tolerability profile.
• No unexpected safety signals were observed during the study.

Ongoing Global Clinical Development

Lunbotinib is also being evaluated in an ongoing international Phase 1/2 study (EP0031-101; NCT05443126) taking place in the United States, Europe, the United Kingdom, and the United Arab Emirates.

The current phase 2 cohort is investigating lunbotinib in combination with platinum-doublet chemotherapy for patients with RET fusion-positive NSCLC who are new to treatment with selective RET inhibitors (treatment naïve).

Phase 3 AcceleRET-Lung Trial Shows Pralsetinib Improves Outcomes in RET Fusion-Positive NSCLC

At the 2026 ASCO Annual Meeting, Dr. Sanjay Popat presented the final results from the Phase 3 AcceleRET-Lung trial, evaluating GAVRETO® (pralsetinib) as a first-line treatment for patients with RET fusion-positive advanced or metastatic non-small cell lung cancer (NSCLC). The study compared pralsetinib with the current standard of care (SOC), consisting of platinum-based chemotherapy with or without immunotherapy.

Overall, these findings support the use of pralsetinib as a first-line treatment option for RET fusion-positive NSCLC, consistent with current clinical guidelines.

About the Study Population:

Most patients enrolled in the trial were from Europe (71%). The majority had little or no smoking history, with 59% never smokers and 30% former smokers. This reflects the patient population commonly seen in RET fusion-positive lung cancer.

Efficacy:

Pralsetinib demonstrated a significant improvement compared with standard treatment:

• Median progression-free survival (PFS): 18.7 months with pralsetinib vs. 9.0 months with standard of care
• Objective Response Rate (ORR): 65.5% with pralsetinib vs. 41.6% with standard of care
• Median Duration of Response (DOR): 20.6 months with pralsetinib vs. 9.7 months with standard of care
• Overall Survival: At the time of analysis, overall survival (OS) data were not yet mature enough to draw definitive conclusions. More than 70% of patients in both treatment arms were still alive at the end of the study, and approximately 34% of patients assigned to standard treatment crossed over to receive pralsetinib after disease progression, which may influence future OS analyses.

Safety and Side Effects:

The safety profile of pralsetinib was generally consistent with previous studies. The most commonly reported side effects included:

• Anemia
• Hypertension
• Pneumonia

Treatment discontinuation due to side effects occurred in 16% of patients receiving pralsetinib and 24% of patients receiving standard of care

Dose interruptions or reductions were reported in 74% of patients receiving pralsetinib and 54% of patients receiving standard of care

Infection Risk and Protocol Changes:

During the trial, eight infection-related deaths occurred among patients receiving pralsetinib. In response, the study protocol was amended in 2024 to include enhanced infection monitoring and earlier intervention for patients showing signs of infection.

Importantly, after these measures were implemented:

• 28 patients remained on treatment under the updated monitoring protocol
• No additional infection-related deaths were reported in this group

These findings suggest that proactive monitoring and prompt management may help reduce the risk of serious infections in patients receiving pralsetinib.

Patients experienced longer periods without disease progression, higher response rates, and more durable responses compared with standard treatment options. The study also highlights the importance of ongoing vigilance regarding infection risk and demonstrates how enhanced monitoring strategies can improve patient safety while maintaining access to effective targeted therapies.

Final Analysis of the ARROW Study: Pralsetinib Shows Durable Responses in RET-Altered Thyroid Cancers

Dr. Vivek Subbiah presented the final results of the phase 1/2 ARROW trial designed to evaluate the long-term efficacy and safety of pralsetinib in patients with RET-altered thyroid cancers.

The international phase 2 ARROW study enrolled patients from 84 sites across 13 countries. Researchers assessed treatment response and safety in patients with advanced or metastatic thyroid cancer (TC) and medullary thyroid cancer (MTC) who received pralsetinib.

At the time of the analysis (May 2024), 145 patients with RET-mutant MC and 28 patients with RET fusion-positive TC received pralsetinib.

Efficacy Findings:

• In patients with RET-mutant medullary thyroid cancer (MTC), the overall response rate (ORR) was 79% among treatment-naïve patients (n=62) and 57% among those previously treated with cabozantinib and/or vandetanib (C/V) (n=60). The median duration of response (DOR) was not reached in the treatment-naïve group and was 21.7 months in the previously treated group.
• Among patients with RET fusion-positive thyroid cancer (TC) (n=24), the ORR was 92%, and the median DOR was not reached, indicating durable responses.
• The median treatment duration was approximately 24.7 months for patients with TC and 35.4 months for those with MTC, reflecting sustained long-term treatment exposure.

These results demonstrate strong and durable antitumor activity, particularly in patients with RET-altered thyroid cancer.

Safety Profile:

Treatment-related adverse events were common but generally consistent with previous reports:

• 96% of TC patients and 98% of MTC patients experienced treatment-related side effects.
• Approximately 66% of patients experienced grade 3 or higher adverse events.
• The most frequent side effects included:
  • Elevated liver enzymes (AST and ALT)
  • Decreased white blood cell counts
  • Anemia

Serious treatment-related deaths were rare, with one case of liver injury in a thyroid cancer patient and one case of pneumonia in a medullary thyroid cancer patient.

Phase I Study: APS03118 in RET Fusion-Positive NSCLC

A Phase I study conducted only in China evaluated APS03118, a next-generation RET inhibitor  in patients with advanced RET fusion-positive NSCLC, including treatment-naïve patients and those previously treated with selective RET inhibitors (SRIs).

APS03118 demonstrated strong clinical activity, with an objective response rate (ORR) of 80% in treatment-naïve patients, 55% in patients previously treated with systemic therapy, and encouraging responses in some patients whose disease had progressed on prior RET inhibitors. Notably, tumor shrinkage of up to 50% was observed in patients with RET resistance mutations (G810S and G810C), suggesting potential activity against known resistance mechanisms.

The treatment showed a manageable safety profile, with mostly reversible elevations in muscle and liver enzymes, supporting further clinical development of APS03118 for RET fusion-positive NSCLC. The studies are being conducted in China only.

Phase III Trial: Soxataltinib in First-Line RET Fusion-Positive NSCLC

A pivotal Phase III trial conducted in China evaluated soxataltinib (SY-5007), a highly selective RET inhibitor, as a first-line treatment for patients with advanced RET fusion-positive NSCLC.

The study showed very high response rates, with an objective response rate (ORR) of 90.0% in the key efficacy population and 87.4% in the overall study population, while median progression-free survival and duration of response had not yet been reached. Disease control rates exceeded 93%, and the majority of patients maintained durable responses and disease control beyond one year of treatment.

Soxataltinib was generally well tolerated, with manageable side effects and no treatment-related deaths or permanent treatment discontinuations, supporting its potential as a best-in-class RET inhibitor in the first-line setting. The studies are being conducted in China only.