Patritumab Deruxtecan BLA Withdrawn in Non-Small Cell Lung Cancer

The FDA application for patritumab deruxtecan in treated EGFR-mutant lung cancer was withdrawn after confirmatory trial data missed survival goals.

The biologics license application (BLA) seeking accelerated approval for patritumab deruxtecan (HER3-DXd) for adult patients with previously treated, locally advanced/metastatic EGFR-mutated non-small cell lung cancer (NSCLC) in the U.S. has been voluntarily withdrawn.

This decision is based on data from the confirmatory phase 3 HERTHENA-Lung02 trial, according to a news release from Merck, which announced the withdrawal.

“EGFR-mutated non-small cell lung cancer has proven to be difficult-to-treat in the second-line metastatic setting and beyond,” said Dr. Ken Takeshita, Global Head of R&D at Daiichi Sankyo, stated in the news release. “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.”

“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,” continued Dr. Eliav Barr, senior vice president, head of Global Clinical Development, and chief medical officer at Merck Research Laboratories. “We would like to thank the patients, their families and investigators for their participation in this study.”

Diving into the Data that Lead to the Withdrawal

Topline overall survival data from HERTHENA-Lung02 fueled the decision to withdraw the patritumab deruxtecan BLA in this patient population, as the overall survival results did not meet statistical significance. Discussions with the U.S. Food and Drug Administration (FDA) supported the regulatory withdrawal, as well. Notably, the complete response letter that Merck received from the FDA in June of 2024 is not related to this withdrawal, as the letter detailed findings pertaining to an inspection of a third-party manufacturing facility, according to the news release.

More information on the phase 3 trial which led to the withdrawal will be shared during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on Sunday, June 1, 2025, where investigators will also share previously reported statistically significant progression-free survival in addition to topline overall survival results.

“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 news release said on safety with patritumab deruxtecan.

The global, multicenter, open-label HERTHENA-Lung02 trial is investigating the efficacy and safety of patritumab deruxtecan monotherapy (5.6 milligrams per kilogram [mg/kg]) every three weeks) monotherapy compared with the four cycles of doublet chemotherapy consisting of platinum plus pemetrexed induction followed by pemetrexed maintenance. This is being evaluated in patients with advanced NSCLC harboring EGFR mutations (exon 19 deletion or L858R) whose disease has progressed following treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI).

Per the study protocol, patients who experience a tumor response will continue treatment with either patritumab deruxtecan or chemotherapy until disease progression, as determined by the investigator. Contrarily, for patients on receiving the chemotherapy regimen without disease progression after four cycles are allowed to continue maintenance pemetrexed treatment with no restriction on the number of cycles

The primary end point of the trial is progression-free survival as evaluated by blinded independent central review (BICR). Secondary end points include overall survival, objective response rate, duration of response, clinical benefit rate, time to response, disease control rate and safety. Brain imaging was performed for enrolled patients to enable evaluation of intracranial end points, including intracranial progression-free survival as determined by BICR.

Across Asia, Europe, North America and Oceania, HERTHENA-Lung02 enrolled 586 patients.

More Information on EGFR-Mutated NSCLC and Patritumab Deruxtecan

In 2022, approximately 2.5 million lung cancer cases were diagnosed globally. Lung cancer remains the most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Non–small cell lung cancer (NSCLC) represents approximately 87% of all lung cancer cases, and in the United States and Europe, approximately up to 15% of patients with NSCLC have an EGFR mutation.

For patients whose tumors harbor EGFR mutations, the standard first-line treatment in the metastatic setting includes EGFR-targeted therapy, with or without platinum-based chemotherapy, improving patient outcomes. However, disease progression occurs in most cases, necessitating additional lines of therapy.

To address this unmet need, investigators are evaluating patritumab deruxtecan. The agent is an investigational antibody-drug conjugate targeting HER3 and consists of a fully human anti-HER3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload through cleavable tetrapeptide-based linkers.

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