For the treatment of locally advanced or metastatic EGFR-mutated non-small cell lung cancer, patritumab deruxtecan did not meet statistical significance for overall survival in the HERTHENA-Lung02 trial.
BLA withdrawn due to lack of OS benefit: The Phase III HERTHENA-Lung02 trial failed to meet its overall survival endpoint, prompting BLA withdrawal.
Regulatory decision unrelated to safety: FDA’s CRL cited manufacturing inspection findings, not clinical efficacy or safety concerns.
Patient stratification in focus: Biomarker analyses are underway to refine future trial populations and optimize therapeutic outcomes.
Daiichi Sankyo and Merck have voluntarily withdrawn their Biologics License Application (BLA) based on the HERTHENA-Lung01 Phase II clinical trial for the accelerated approval of patritumab deruxtecan (HER3-DXd) in the US. The decision to pull back the BLA is based on data from the Phase III HERTHENA-Lung02 study of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies.1
In the confirmatory HERTHENA-Lung02 trial (NCT05338970), patritumab deruxtecan did not meet statistical significance for overall survival (OS). According to the companies, the decision to withdraw its BLA was not related to the FDA’s Complete Response Letter (CRL) received in June 2024. While the CRL did not identify any issues with efficacy or safety, it referenced findings pertaining to an inspection of a third-party manufacturing facility.2
In a press release, Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, said: “EGFR-mutated non-small cell lung cancer has proven to be difficult-to-treat in the second-line metastatic setting and beyond. While we are disappointed with the overall survival results of HERTHENA-Lung02, we are conducting further biomarker analyses to better identify patients that may benefit from patritumab deruxtecan to guide our continued development in lung cancer. We remain confident in the broad development program of this HER3 directed antibody drug conjugate, which currently includes multiple clinical trials across 15 types of cancer.”1
Patritumab deruxtecan was discovered by Daiichi Sankyo and is being jointly developed by both Daiichi Sankyo and Merck. It is a specifically engineered HER3 directed DXd antibody drug conjugate.
The now withdrawn BLA was based on positive results from the Phase II HERTHENA-Lung01 trial (NCT04619004). Daiichi Sankyo shared data from the study in September 2023. Patritumab deruxtecan demonstrated clinically meaningful and durable responses in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy.3
In the trial, patritumab deruxtecan showed a confirmed objective response rate (ORR) of 29.8% in 225 patients with EGFR-mutated NSCLC. Additional results include a median duration of response of 6.4 months, a disease control rate of 73.8%, a median progression-free survival (PFS) of 5.5 months, and a median OS of 11.9 months.
Meanwhile, Daiichi Sankyo and Merck shared results from the HERTHENA-Lung02 trial in September 2024. While OS data were immature at the time of this analysis, the study met its primary endpoint of PFS by demonstrating a statistically significant improvement versus platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy.4
HERTHENA-Lung01 enrolled 277 patients in Asia, Europe, North America, Oceania, while HERTHENA-Lung02 enrolled 586 patients across the same regions. HERTHENA-Lung01 featured an additional arm for uptitration regimen. However, the arm was later discontinued following a risk-benefit analysis conducted from a separate Phase I study which selected the 5.6 mg/kg dose of patritumab deruxtecan.
In the press release announcing the withdrawn BLA, Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said: “Lung cancer is one of the leading causes of cancer-related deaths worldwide and these results are a reminder of how challenging it can be to treat patients with EGFR-mutated non-small cell lung cancer in the second and later line settings. We would like to thank the patients, their families and investigators for their participation in this study.”1
1. Patritumab Deruxtecan Biologics License Application for Patients with Previously Treated Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer Voluntarily Withdrawn. Daiichi Sankyo and Merck. News release. May 29, 2025. Accessed May 29, 2025. https://www.businesswire.com/news/home/20250529890099/en/Patritumab-Deruxtecan-Biologics-License-Application-for-Patients-with-Previously-Treated-Locally-Advanced-or-Metastatic-EGFR-Mutated-Non-Small-Cell-Lung-Cancer-Voluntarily-Withdrawn
2. Patritumab Deruxtecan BLA Submission Receives Complete Response Letter from FDA Due to Inspection Findings at Third-Party Manufacturer. Daiichi Sankyo. News release. June 26, 2024. Accessed May 29, 2025. https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer
3. Patritumab Deruxtecan Demonstrated Clinically Meaningful and Durable Responses in Patients with EGFR-Mutated Metastatic Non-Small Cell Lung Cancer in HERTHENA-Lung01 Phase 2 Trial. News release. Daiichi Sankyo. September 10, 2023. Accessed May 29, 2025. https://daiichisankyo.us/press-releases/-/article/patritumab-deruxtecan-demonstrated-clinically-meaningful-and-durable-responses-in-patients-with-egfr-mutated-metastatic-non-small-cell-lung-cancer-in-
4. 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. Daiichi Sankyo and Merck. News release. September 17, 2024. Accessed May 29, 2025. https://www.businesswire.com/news/home/20240917471670/en/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
Unifying Industry to Better Understand GCP Guidance
May 7th 2025In this episode of the Applied Clinical Trials Podcast, David Nickerson, head of clinical quality management at EMD Serono; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, discuss the newest ICH E6(R3) GCP guidelines as well as how TransCelerate and ACRO have partnered to help stakeholders better acclimate to these guidelines.
