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FDA Issues Complete Response Letter to Merck and Daiichi Sankyo for Patritumab Deruxtecan for Advanced, Metastatic EGFR-Mutated Non-Small Cell Lung Cancer


The Complete Response Letter was issued as a result of inspection findings at a third-party manufacturing facility, unrelated to patritumab deruxtecan’s efficacy or safety in patients with advanced or metastatic EGFR-mutated non-small cell lung cancer.

Diseases of the lungs in the picture lung cancer concept. Image Credit: Adobe Stock Images/CraftyImago

Image Credit: Adobe Stock Images/CraftyImago

The FDA has issued a Complete Response Letter (CRL) to Merck and Daiichi Sankyo regarding their Biologics License Application (BLA) for patritumab deruxtecan, a treatment for advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). According to the companies, the CRL resulted from inspection findings at a third-party manufacturing facility and was not related to the drug's efficacy or safety.1

“We will work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible in order to bring the first HER3 directed medicine to patients with previously treated EGFR-mutated non-small cell lung cancer,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in a press release. “We remain confident in the ability to develop this medicine to its full potential.”

Initially granted Breakthrough Therapy Designation in 2021, the BLA for patritumab deruxtecan was accepted by the FDA based on results from the global, multicenter, open-label, two-arm HERTHENA-Lung01 Phase II trial evaluating the safety and efficacy of the medication in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR tyrosine kinase inhibitor and platinum-based chemotherapy. As part of the trial, 225 patients were split up to receive either 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The primary endpoint of the trial was objective response rate (ORR) as assessed by blinded independent central review (BICR), with secondary endpoints including duration of response (DoR), progression-free survival, disease control rate, and time to response— which were also evaluated by BICR and investigator assessment—and investigator-assessed ORR, overall survival, safety and tolerability.

Results found an ORR of 29.8% in patients treated with patritumab deruxtecan. Additionally, there was one complete response reported and 66 partial responses, with a median DoR of 6.4 months.

The safety profile of patritumab deruxtecan remained consistent with previous studies, with 7.1% of trial participants discontinuing treatment as a result of treatment-emergent adverse events (TEAEs), while Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common TEAEs of this grade were thrombocytopenia, neutropenia, anemia, leukopenia, fatigue, hypokalemia, and asthenia. Investigators found that 5.3% of patients had confirmed treatment-related interstitial lung disease (ILD), with one grade 5 ILD reported.1,2

“The FDA’s prioritization of the BLA submission reflects the strength of the data from HERTHENA-Lung01 and emphasizes the need to provide new options to patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer previously treated with two or more systemic therapies,” said Takeshita, in an earlier press release. “If approved, patritumab deruxtecan could become the first HER3-directed medicine approved in the US and the second DXd antibody drug conjugate approved from Daiichi Sankyo’s oncology pipeline.”

According to Merck, an estimated 226,000 lung cancer cases were diagnosed in the United States in 2022, making it the third most common cancer in the country and the leading cause of cancer-related deaths. Additionally, NSCLC makes up 81% of all lung cancers in the United States. Further, Merck reported that EGFR mutations occur in one out of every five patients with NSCLC in Western countries.1

“Patients with previously treated EGFR-mutated non-small cell lung cancer often experience recurrence and have limited treatment options,” said Marjorie Green, MD, SVP, head of oncology, global clinical development, Merck Research Laboratories, in the press release. “We are committed to working with Daiichi Sankyo and the FDA to prioritize making patritumab deruxtecan available to these patients in need.”


1. Complete Response Letter from FDA Due to Inspection Findings at Third-Party Manufacturer. Merck. June 26, 2024. Accessed June 27, 2024. https://www.merck.com/news/patritumab-deruxtecan-bla-submission-receives-complete-response-letter-from-fda-due-to-inspection-findings-at-third-party-manufacturer/

2. Patritumab Deruxtecan Granted Priority Review in the U.S. for Certain Patients with Previously Treated Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer. Merck. December 22, 2023. Accessed June 27, 2024. https://www.merck.com/news/patritumab-deruxtecan-granted-priority-review-in-the-u-s-for-certain-patients-with-previously-treated-locally-advanced-or-metastatic-egfr-mutated-non-small-cell-lung-cancer/

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