FDA BLA Pulled for Patritumab Deruxtecan in EGFR+ NSCLC
The FDA biologics license application for patritumab deruxtecan in EGFR+ NSCLC has been withdrawn following discussions with the agency.
US FDA
- Merck has voluntarily withdrawn its biologics license application (BLA) for patritumab deruxtecan (HER3-DXd) in previously treated EGFR-mutated advanced non–small cell lung cancer (NSCLC).
- The application had sought accelerated approval for patients who had received ≥2 prior lines of systemic therapy.
- This decision is based on data from the phase 3 HERTHENA-Lung02 trial (NCT05338970).
The FDA biologics license application for patritumab deruxtecan in previously treated EGFR-mutated advanced NSCLC has been voluntarily withdrawn following the agency’s discussions with Merck.1
The decision follows topline overall survival (OS) data from the phase 3 HERTHENA-Lung02 trial, which did not meet the OS statistical threshold, a key requirement for conversion to full approval. While discussions with the FDA factored into the withdrawal, it is not related to the June 2024 complete response letter regarding third-party manufacturing inspection.
Notably, HERTHENA-Lung02 had previously shown a statistically significant improvement in progression-free survival (PFS) with patritumab deruxtecan vs platinum/pemetrexed-based chemotherapy.2 However, OS data were immature at that earlier time point.
Further, safety findings from the HERTHENA-Lung02 study showed the profile of patritumab deruxtecan to be consistent with that seen in prior studies of the agent in patients with lung cancer, and no new safety signals were observed.1
“EGFR-mutated NSCLC has proven to be difficult to treat in the second-line metastatic setting and beyond,” said Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, stated in a press release.1 “While we are disappointed with the OS 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.”
Additional data from the HERTHENA-Lung02 trial will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
About the HERTHENA-Lung02 Trial
The randomized, open-label, phase 3 HERTHENA-Lung02 enrolled adult patients with EGFR-mutated metastatic or locally advanced NSCLC after disease progression on 1 or 2 prior lines of an approved EGFR tyrosine kinase inhibitor (TKI) in the metastatic or locally advanced setting, including a third-generation TKI.3
Enrollment in the study was open to patients with at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate bone marrow and organ function. Patients treated with any other prior systemic therapies in the metastatic or locally advanced setting were not eligible for enrollment. Further, patients were eligible to receive neoadjuvant and/or adjuvant therapy if disease progression occurred at least 12 months after receiving the final dose of a third-generation TKI.
Once enrolled, patients were randomly assigned to receive patritumab deruxtecan via intravenous (IV) infusion at a dose of 5.6 mg/kg every 3 weeks or platinum-based chemotherapy. In the chemotherapy arm, patients were given 500 mg/m2 of IV pemetrexed plus 75 mg/m2 of cisplatin or carboplatin for a target area under the plasma concentration time curve of 5 once every 3 weeks.
For those in the chemotherapy arm, treatment continued for 4 cycles. Patients without disease progression after 4 cycles were permitted to continue receiving treatment with maintenance pemetrexed with no restriction on the number of cycles.
PFS per blinded independent central review per RECIST 1.1 criteria served as the study’s primary end point. Secondary end points consisted of OS, PFS as assessed by the investigator, objective response rate, duration of response, clinical benefit rate, disease control rate, time to response, intracranial PFS, quality of life, and safety.
“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 these patients with EGFR-mutated NSCLC in the second and later line settings,” said Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, in the press release. “We would like to thank the patients, their families, and investigators for their participation in this study.”
