Epidermal growth factor receptor (EGFR) gene mutations are the most common oncogenic driver mutations in non-small cell lung cancer (NSCLC) patients in China, with a significantly higher incidence compared to Caucasian populations. At the recent ESMO Asia Congress 2024, Dr. Li Zhang from the Sun Yat-sen University Cancer Center presented results from the Phase II BOOSTER clinical trial investigating Becotarug (JMT101) combined with Osimertinib for the treatment of classic EGFR-mutant NSCLC patients. Oncology Frontier interviewed Professor Zhang to discuss the background and key findings of this study.

Oncology Frontier: EGFR exon 20 insertion mutations (ex20ins) rank third among EGFR gene mutations, following exon 19 deletion (ex19del) and exon 21 L858R point mutations. Could you elaborate on the occurrence of EGFR 20ins and the unmet medical needs for patients with this mutation? Please share insights into your research in this area.

Dr. Li Zhang: The significant progress in targeted therapies for NSCLC has greatly improved patient outcomes and quality of life. However, compared to patients with common EGFR mutations, those with EGFR exon 20 insertions have poorer prognoses and derive limited benefits from EGFR-TKI therapies.

Currently, first-line treatment for advanced NSCLC patients with ex20ins primarily involves chemotherapy. Approved targeted therapies are only available for second-line or later treatments. In China, the only second-line targeted option is Sunvozertinib, while internationally, amivantamab—a bispecific antibody targeting EGFR and MET—is also available. The U.S. FDA initially approved amivantamab monotherapy for second-line treatment based on CHRYSALIS study data and recently approved its combination with chemotherapy (carboplatin and pemetrexed) for first-line treatment based on the PAPILLON trial.

Two years ago, we initiated a study combining Becotarug, a humanized IgG1 monoclonal antibody targeting EGFR, with Osimertinib in NSCLC patients carrying EGFR 20ins mutations, yielding promising results. The Phase II BECOME trial, presented at the 2024 ELCC conference, showed an objective response rate (ORR) of 50% in the intention-to-treat (ITT) population, a median progression-free survival (PFS) of 6.9 months, and a median overall survival (OS) of 17.2 months—comparable to the efficacy of Sunvozertinib in second-line therapy. We are now conducting a Phase III trial comparing Becotarug plus Osimertinib versus chemotherapy (cisplatin plus pemetrexed) as a first-line treatment, hoping this innovative therapy offers new hope and possibilities for EGFR ex20ins patients.

Oncology Frontier: At ESMO ASIA 2024, you presented the results of the Phase II BOOSTER trial (Abstract No. 614MO), where you served as the principal investigator. This study focused on classic EGFR-mutant NSCLC. Could you share details on the BOOSTER study design and its latest results?

Dr. Li Zhang: After observing promising outcomes of the Becotarug regimen in the rare EGFR 20ins patient group, the BOOSTER trial took a step forward by exploring this regimen in the broader population of classic EGFR-mutant NSCLC patients.

We know that amivantamab has been approved not only for EGFR 20ins mutations but has also shown positive results in the MARIPOSA study, where it was combined with the third-generation EGFR-TKI lazertinib for first-line treatment of EGFR-mutant advanced NSCLC, and in the MARIPOSA-2 study for second-line treatment combined with chemotherapy ± lazertinib. Similarly, we extended the use of Becotarug to EGFR-mutant advanced NSCLC patients.

In the Phase II BOOSTER trial, Becotarug was combined with the third-generation EGFR-TKI Osimertinib to treat patients with typical EGFR-mutant NSCLC across multiple cohorts. In the cohort of 33 newly diagnosed stage IV EGFR-mutant NSCLC patients, the combination of Becotarug (6 mg/kg every 3 weeks) and Osimertinib (80 mg daily) achieved an ORR of 78.8%, a disease control rate (DCR) of 81.8%, and a median PFS of 20.8 months (data not yet mature). The median OS has not been reached. The incidence of all-grade adverse events (AEs) was 100%, with grade ≥3 AEs at 30.3% and serious AEs at 15.2%.

Although the PFS and OS follow-up data from the BOOSTER trial are still immature, the efficacy is comparable to the MARIPOSA and FLAURA2 studies. Notably, the BOOSTER trial showed no infusion reactions, interstitial lung disease, or venous thrombosis, which are common adverse events in similar treatments.

Based on the Phase II BOOSTER results, we have initiated a Phase III trial to evaluate Becotarug combined with Osimertinib versus Osimertinib alone as first-line therapy for patients with EGFR-mutant locally advanced or metastatic non-squamous NSCLC. We eagerly anticipate that the Phase III trial will provide better treatment options for these patients.

Dr. Li Zhang

• Second-level Professor, Chief Physician of Internal Medicine
• Doctoral Supervisor, Chief Lung Cancer Expert
• Deputy Director, Lung Cancer Research Institute, Sun Yat-sen University
• Chair, Tumor Rehabilitation and Palliative Care Committee, Chinese Anti-Cancer Association
• Vice Chair, Clinical Trial Committee, Chinese Anti-Cancer Association
• Executive Director, Chinese Society of Clinical Oncology (CSCO)
• Chair-Elect, CSCO Immunotherapy Expert Committee
• Chair, Chemotherapy Committee, Guangdong Anti-Cancer Association
• Vice Chair, Lung Cancer Committee, Guangdong Anti-Cancer Association
• Guangdong Provincial Leading Medical Talent, “Special Support Plan” Distinguished Talent (Nan Yue Top 100)
• Principal Investigator, National Key R&D Program on Precision Medicine Research for Lung Cancer Diagnosis and Treatment