While the ESMO 2023 annual meeting is close, pharma companies, namely Janssen, AstraZeneca, Roche, Boehringer Ingelheim, Daiichi Sankyo, Yuhan Corporation, and others are looking at this opportunity to present the data readouts of their therapies for EGFR NSCLC. The 2023 ESMO Annual Meeting Program will offer presentations on the latest research in cancer care. DelveInsight, maintaining an essence of brevity, has compiled some of the important EGFR NSCLC therapies abstracts while discussing a few. 

Therapies for EGFR NSCLC Therapy Highlights

1. Abstract Number – #LBA5, #LBA14, and #LBA15

• Abstract Type – Proffered Paper Session (LBA)
• Indication – NSCLC
• Target – EGFR-mutated Advanced NSCLC

Title: Janssen's Advances in EGFR-mutated NSCLC: ESMO 2023 Unveils a New Horizon

Executive Summary – Janssen Pharmaceuticals is set to revolutionize NSCLC treatment with groundbreaking data from their PAPILLON, MARIPOSA, and MARIPOSA-2 trials. RYBREVANT (amivantamab-vmjw), in combination with innovative approaches, demonstrates statistically significant advancements, ushering in a new era for EGFR-mutated and EGFR-positive NSCLC care.

Main Content – Janssen's Phase III PAPILLON study marks a significant milestone by assessing RYBREVANT in combination with carboplatin-pemetrexed against carboplatin-pemetrexed alone as first-line treatment for patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. Topline data showed a statistically significant and clinically meaningful advancement in PFS, cementing the potential of RYBREVANT in reshaping the treatment landscape for these challenging mutations.

Two other trials being investigated by Janssen include the MARIPOSA and MARIPOSA-2 study Janssen's Phase III MARIPOSA study is set to disrupt the paradigm of EGFR-positive NSCLC treatment. This pivotal trial evaluates RYBREVANT in combination with the novel third-generation EGFR TKI, lazertinib. The study compares this combination against osimertinib and lazertinib alone in first-line treatment. Early findings revealed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients receiving RYBREVANT plus lazertinib, thus challenging the status quo of NSCLC care.

In the Phase III MARIPOSA-2 study, Janssen investigates the efficacy of RYBREVANT with or without lazertinib in combination with carboplatin-pemetrexed, compared to carboplatin-pemetrexed alone. Promisingly, topline data from this trial showed statistically significant and clinically meaningful PFS improvements in patients who received RYBREVANT combined with chemotherapy, both with and without lazertinib, after experiencing disease progression post-osimertinib treatment.

The MARIPOSA trial's clinical results would be crucial in whether RYBREVANT would triumph against AstraZeneca's rival. Additionally, RYBREVANT will have access to a larger patient cohort through the MARIPOSA-2 study, which accounts for up to 90% of all EGFR mutations in NSCLC. However, it is important to note that RYBREVANT may have an uphill struggle against TAGRISSO.

2 Abstract Number – #LBA68

• Abstract Type – Mini Oral Session 
• Indication – NSCLC
• Target – EGFR-mutated Advanced NSCLC

Title: FLAURA2 Trial Breakthrough: TAGRISSO Combo Delivers Impressive Results in EGFR mutated Lung Cancer Treatment

Executive Summary – In the FLAURA2 Phase III trial, TAGRISSO combined with chemotherapy significantly improves progression-free survival, even in patients with central nervous system metastases. While overall survival data is pending, the safety profile is manageable, marking a promising development in first-line NSCLC treatment.

Main Content – In the FLAURA2 Phase III trial, TAGRISSO in combination with chemotherapy reduced the risk of disease progression or death by 38% compared to TAGRISSO monotherapy, the first-line global standard of care. By investigator assessment, the combination extended median PFS by 8.8 months versus TAGRISSO alone. PFS results from the blinded independent central review were consistent, showing the drug plus chemotherapy extended median PFS by 9.5 months. Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including patients with central nervous system metastases. In this group, the combination reduced the risk of disease progression or death by 53% compared to TAGRISSO monotherapy, extending median PFS by 11.1 months versus TAGRISSO alone. At the time of this analysis, the OS data were immature, however, a favorable trend was observed for TAGRISSO plus chemotherapy. The trial continues to assess OS as a key secondary endpoint. The safety profile of TAGRISSO plus chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event rates were higher in the combination arm, driven by well-characterized chemotherapy-related adverse events. Additional safety information will be presented at a forthcoming meeting.

The US FDA has granted a priority review to the supplemental new drug application (sNDA) filed by AstraZeneca for TAGRISSO, in combination with chemotherapy, to treat adults with locally advanced or metastatic EGFR-mutated NSCLC. In August 2023, the company also received a breakthrough therapy designation from the US FDA for TAGRISSO in the same indication.

The drug combination with chemotherapy is estimated to generate a market of  ~USD 19 million in the first line setting in 2024 in the United States. The drug is also estimated to enter the second line in 2024 in the United States and generate a revenue of ~USD 1 million in the launch year.

 

3 Abstract Number – #LBA12

• Abstract Type – Proffered Paper Session 
• Indication – NSCLC
• Technology – DXd ADC technology

Title: Revolutionizing EGFR NSCLC Treatment: Dato-DXd Shines in TROPION-Lung01 Phase III Trial

Executive Summary –  The TROPION-Lung01 Phase III trial reveals datopotamab deruxtecan (Dato-DXd) as a promising breakthrough for EGFR NSCLC treatment, showing significant progress in progression-free survival compared to chemotherapy. This milestone trial signifies a potential paradigm shift in lung cancer care, offering renewed hope for patients in need.

Main Content – In a groundbreaking revelation, the TROPION-Lung01 Phase III trial has unveiled compelling results for the treatment of EGFR NSCLC. The trial showcases datopotamab deruxtecan (Dato-DXd) as a shining beacon of hope for patients battling locally advanced or metastatic NSCLC who have previously undergone therapy. This study has demonstrated a statistically significant improvement in progression-free survival (PFS) when compared to the current standard of care chemotherapy, docetaxel. While the data for OS is yet to reach maturity, early indications favor Dato-DXd over docetaxel. The trial will persist as planned, ensuring OS is rigorously assessed along with the safety profiles. The incidence of interstitial lung disease, even with some Grade 5 events, remains consistent with earlier trials, primarily in the low-grade category. The triumph of TROPION-Lung01 marks a significant milestone in the pursuit of alternatives to chemotherapy for previously treated and unselected patients. Dato-DXd challenges the entrenched standard of care, offering a ray of hope where one was long overdue. 

Datopotamab deruxtecan is estimated to enter the market in 2024 and generate a revenue of ~USD 0.4 million in the United States.

Some important abstracts upcoming in the session