Patritumab Deruxtecan BLA Submission Receives Complete Response Letter from FDA Due to Inspection Findings at Third-Party Manufacturer
- The letter did not identify any issues with the efficacy or safety data submitted in the application
The CRL results from findings pertaining to an inspection of a third-party manufacturing facility. The CRL did not identify any issues with the efficacy or safety data submitted.
Patritumab deruxtecan is a specifically engineered potential first-in-class HER3 directed DXd antibody drug conjugate (ADC) discovered by
“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
“Patients with previously treated EGFR-mutated non-small cell lung cancer often experience recurrence and have limited treatment options,” said
The BLA is based on the primary results from the HERTHENA-Lung01 pivotal phase 2 trial that were presented at the IASLC 2023
In HERTHENA-Lung01, patritumab deruxtecan was studied in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy, which demonstrated an objective response rate (ORR) of 29.8% (95% CI: 23.9-36.2), including one complete response and 66 partial responses. The median duration of response (DoR) was 6.4 months (95% CI: 4.9-7.8).
The safety profile of patritumab deruxtecan observed in HERTHENA-Lung01 was consistent with previous phase 1 clinical trials in NSCLC with a treatment discontinuation rate of 7.1% due to treatment-emergent adverse events (TEAEs). Grade 3 or higher TEAEs occurred in 64.9% of patients. The most common (≥5%) grade 3 or higher TEAEs were thrombocytopenia (21%), neutropenia (19%), anemia (14%), leukopenia (10%), fatigue (6%), hypokalemia (5%) and asthenia (5%). Twelve patients (5.3%) had confirmed treatment-related interstitial lung disease (ILD) as determined by an independent adjudication committee. One grade 5 ILD event was observed.
About HERTHENA-Lung01
HERTHENA-Lung01 is a global, multicenter, open-label, two-arm phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from the phase 1 trial assessing the doses in a similar patient population.
The primary endpoint of HERTHENA-Lung01 was ORR as assessed by blinded independent central review (BICR). Secondary endpoints included DoR, progression-free survival, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, overall survival, safety and tolerability.
HERTHENA-Lung01 enrolled patients in
About EGFR-Mutated Non-Small Cell Lung Cancer
Approximately 226,000 lung cancer cases were diagnosed in the
About HER3
HER3 is a member of the EGFR family of receptor tyrosine kinases.5 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.6,7 HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival.8,9 There is currently no HER3 directed therapy approved for the treatment of any cancer.
About Patritumab Deruxtecan
Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Patritumab deruxtecan was granted Breakthrough Therapy Designation by the
Patritumab deruxtecan is currently being evaluated as both a monotherapy and in combination with other therapies in a global development program, which includes HERTHENA-Lung02, a phase 3 trial evaluating the efficacy and safety of patritumab deruxtecan versus platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression on or after treatment with a third-generation EGFR TKI; HERTHENA-Lung01, a phase 2 trial in metastatic or locally advanced NSCLC with an activating EGFR mutation previously treated with at least one EGFR TKI and one platinum-based chemotherapy-containing regimen; HERTHENA-PanTumor01, a phase 2 trial in locally advanced or metastatic solid tumors, including melanoma, gastric and head and neck cancer, among other types of cancer, previously treated with at least one prior systemic therapy; a phase 1 trial in combination with osimertinib in EGFR-mutated locally advanced or metastatic NSCLC; and a phase 1 trial in previously treated patients with advanced NSCLC. A phase 1/2 trial in HER3 expressing metastatic breast cancer also has been completed.
About the
About the DXd ADC Portfolio of
The DXd ADC portfolio of
Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About
Merck’s Focus on Cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/.
About
At
Forward-Looking Statement of
This news release of
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended
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References:
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3 SEER. Adenocarcinoma of the Lung and Bronchus Stage Distribution of SEER Incidence Cases. 2012-2021. Accessed
4 Tan AC, et al. J Clin Oncol. 2022;40(6):611-625.
5 Mishra R, et al. Onco Rev. 2018; 12(355):45-62.
6 Scharpenseel H, et al. Scientific Reports. 2019; 9:7406.
7 Yonesaka K, et al.
8 Gandullo-Sánchez L et al. J Exp Clin Cancer Res. 2022; 41:310.
9 Yu H.A., et al. Annals of Oncology. 2024; 35(5): P437-447.
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