Patritumab deruxtecan demonstrates a statistically significant progression-free survival improvement in this EGFR-mutated non-small cell lung cancer population with high unmet need following prior EGFR TKI treatment
The HERTHENA-Lung02 phase III trial evaluating patritumab deruxtecan in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who received prior EGFR tyrosine kinase inhibitor (TKI) treatment met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement versus platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy
Overall survival (OS) data were immature at the time of the analysis and the trial will continue to further assess OS, a secondary endpoint. Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck( known as MSD outside of the United States and Canada).
NSCLC accounts for approximately 85% of all lung cancers worldwide with up to 70% of NSCLC cases diagnosed at an advanced stage and EGFR-activating mutations occur in 14% to 38% of all NSCLC tumors worldwide. Following initial treatment for metastatic EGFR-mutated NSCLC with an EGFR TKI, many patients experience disease progression and currently available therapies in the second-line setting are limited, highlighting the need for new approaches to improve outcomes. Data from the HERTHENA-Lung02 trial will be presented at an upcoming medical meeting and shared with global regulatory authorities.
“We are encouraged by these results demonstrating a statistically significant progression-free survival improvement compared to platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer who received prior tyrosine kinase inhibitor treatment,” said Marjorie Green, MD, Senior Vice President and Head of Oncology, Global Clinical Development, Merck. “Together with Daiichi Sankyo, we are committed to helping patients with previously treated EGFR-mutated non-small cell lung cancer, where there is a high unmet need.”
The safety profile seen in HERTHENA-Lung02 was consistent with that observed for patritumab deruxtecan in previous lung cancer clinical trials with no new safety signals identified. The majority of interstitial lung disease (ILD) events were low grade (grade 1 and 2). There were two grade 5 ILD events observed.
About HERTHENA-Lung02: HERTHENA-Lung02 is a global, multicenter, open-label, phase III trial evaluating the efficacy and safety of patritumab deruxtecan (5.6 mg/kg every three weeks) versus four cycles of pemetrexed and platinum chemotherapy in patients with metastatic or locally advanced NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) after failure of third-generation (e.g., osimertinib, lazertinib, aumolertinib, alflutinib) EGFR TKI therapy. Patients in the comparator arm without disease progression after four cycles of pemetrexed and platinum chemotherapy are able to continue treatment with maintenance pemetrexed with no restriction on the number of cycles.
The primary endpoint of HERTHENA-Lung02 was PFS as assessed by blinded independent central review (BICR). Secondary endpoints included OS, objective response rate, duration of response, clinical benefit rate, time to response, disease control rate, and safety. Patients enrolled in the study underwent brain imaging to allow for assessment of intracranial endpoints, including intracranial PFS as assessed by BICR. HERTHENA-Lung02 enrolled 586 patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov.
About EGFR-Mutated Non-Small Cell Lung Cancer: Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. Lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. Approximately 85% of lung cancer is classified as NSCLC with EGFR-activating mutations occurring in 14 to 38% of all NSCLC tumors worldwide. NSCLC is diagnosed at an advanced stage in up to 70% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy. Following initial treatment for metastatic EGFR-mutated NSCLC with an EGFR TKI, many patients experience disease progression and currently available therapies in the second-line setting are limited, highlighting the need for new approaches to improve outcomes.
About HER3 :HER3 is a member of the HER family of receptor tyrosine kinases. It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment. HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival. There is currently no HER3 directed therapy approved for the treatment of any cancer.
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