Patritumab Deruxtecan Demonstrates Significant Survival Improvement in Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

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Data from the Phase III HERTHENA-Lung02 trial found that patritumab deruxtecan demonstrated a statistically significant improvement in progression-free survival (PFS) in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who received prior EGFR tyrosine kinase inhibitor (TKI) treatment. As part of the trial, the treatment was compared to standard platinum-based doublet chemotherapy According to investigators, the HER3-directed antibody-drug conjugate (ADC) jointly developed by Daiichi Sankyo and Merck demonstrated superior results to platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy.¹

“These results from HERTHENA-Lung02 demonstrate the potential of patritumab deruxtecan to become an important treatment option for certain patients with EGFR-mutated non-small cell lung cancer with prior tyrosine kinase inhibitor treatment,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in a press release. “We plan to share these findings with regulatory authorities to discuss next steps.”

The global, multicenter, open-label, HERTHENA-Lung02 trial evaluated the efficacy and safety of patritumab deruxtecan every three weeks versus four cycles of pemetrexed and platinum chemotherapy in patients with metastatic or locally advanced NSCLC with an EGFR-activating mutation after failure of third-generation EGFR TKI therapy. Consisting of 586 patients across Asia, Europe, North America, and Oceania, the primary endpoint of the study was PFS as assessed by blinded independent central review. Secondary endpoints included overall survival, objective response rate, duration of response, clinical benefit rate, time to response, disease control rate, and safety.

Full results from the trial are expected to be presented at an upcoming medical meeting and shared with global regulatory authorities. The safety profile of patritumab derutecan in the HERTHENA-Lung02 trial was consistent with previous lung cancer clinical trials and no new safety signals were identified.

According to Merck, NSCLC accounts for 85% of lung cancers globally, with EGFR mutations found in 14%-38% of all cases. Further, it is diagnosed in the advanced stages around 70% of the time and often has a poor prognosis, with worsening outcomes after each line of subsequent therapy. Following initial treatment, many patients experience disease progression and currently available therapies in the second-line setting are limited, underscoring the significance of this trial’s results. In 2022, an estimated 2.5 million lung cancer cases were diagnosed globally.¹

According to the Centers for Disease Control and Prevention, lung cancer is the third most common form of cancer in the United States. Additionally, more people die from lung cancer than any other cancer in the United States.2 In 2021, there were 209,500 new cases reported in the United States.3 The American Lung Association states that men are 23% more likely than women to be diagnosed with lung cancer at some point during their lifespan. Despite accounting for the highest cancer death rate, lung cancer only accounts for 3% of patients ever diagnosed with cancer due to its low survival rate compared to other leading cancers.⁴

“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, SVP, head, oncology, global clinical development, Merck, in the press release. “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.”

References

1. Patritumab Deruxtecan Demonstrated Statistically Significant Improvement in Progression-Free Survival Versus Doublet Chemotherapy in Patients with Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer in HERTHENA-Lung02 Phase 3 Trial. Merck. September 17, 2024. Accessed September 19, 2024. https://www.merck.com/news/patritumab-deruxtecan-demonstrated-statistically-significant-improvement-in-progression-free-survival-versus-doublet-chemotherapy-in-patients-with-locally-advanced-or-metastatic-egfr-mutated-non-small/

2. Lung Cancer Statistics. CDC. Accessed September 19, 2024. https://www.cdc.gov/lung-cancer/statistics/index.html

3. Cancer Statistics At a Glance. CDC. Accessed September 19, 2024. https://gis.cdc.gov/Cancer/USCS/#/AtAGlance/

4. Lung Cancer Trends Brief: Prevalence and Incidence. American Lung Association. Accessed September 19, 2024. https://www.lung.org/research/trends-in-lung-disease/lung-cancer-trends-brief/lung-cancer-prevalence-and-incidence-(1)