Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.

Start Date22 Dec 2015

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

NCT02350712

/ CompletedPhase 1

An Open Label, Phase 1B Safety Evaluation of Patritumab (U31287) in Combination With Cetuximab Plus Platinum Containing Therapy In Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

The purpose of this study is to test a study drug called patritumab. Patritumab may work when combined with other medications that are approved in the UK for treating Squamous Cell Carcinoma of the Head and Neck (SCCHN), called cetuximab, cisplatin or carboplatin. It is hoped that patritumab may have some benefit in treating patients with cancer. This study will help identify how much patritumab can be given in combination with cetuximab, and cisplatin or carboplatin. This study will show how safe and how well tolerated patritumab is when these medications are given together.

Start Date01 Dec 2014

Sponsor / Collaborator

Daiichi Sankyo, Inc.

NCT02134015

/ TerminatedPhase 3

Phase 3, Randomized, Placebo-Controlled, Double-Blind, Multi-Center, Two-Part Study of Patritumab (U3-1287) In Combination With Erlotinib in EGFR Wild-type Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on at Least One Prior Systemic Therapy

1. Part A: Subjects will receive Patritumab or placebo with erlotinib. Progression-free survival will be the primary outcome. Subjects will need to have Epidermal Growth Factor Receptor (EGFR) wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2 (Human Epidermal Growth Factor Receptor 2), anti-HER3, or anti-HER4 therapy. Subjects may have high heregulin or low heregulin.
2. Part B: Subjects will receive Patritumab or placebo with erlotinib. Overall survival will be the primary outcome. Subjects will need to have EGFR wild-type, locally advance or metastatic NSCLC and have their cancer progressed after at least one prior systemic anti-cancer therapy, available recent or archival tumor specimen and may not have had previous EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy. Only subjects with high heregulin will be enrolled.

Start Date01 Mar 2014

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

[+1]

100 Clinical Results associated with Patritumab

100 Translational Medicine associated with Patritumab

100 Patents (Medical) associated with Patritumab

Literatures (Medical) associated with Patritumab

01 May 2025·REVUE DES MALADIES RESPIRATOIRES

Pneumopathies interstitielles diffuses induites par les anticorps conjugués

Review

Author: Sagan, C ; Maurier, L ; Pons-Tostivint, E ; Chéné, A-L ; Hulo, P ; Chen, J

INTRODUCTION:

Antibody-drug conjugates (ADCs) represent a promising new therapeutic class in non-small-cell lung cancer (NSCLC) patients. Studies assessing ADC have highlighted a pulmonary toxicity profile in the form of interstitial lung disease (ILD).

STATE OF THE ART:

Several ADCs for NSCLC are currently being developed. In studies evaluating Trastuzumab-Deruxtecan (Her-2 target), incidence of drug-induced ILD ranged from 10.7 to 26.0%, and from 3.6 to 25.0% in those evaluating Datopotamab-Deruxtecan (TROP-2 target). Incidence of 9.9 and 5% of ILD was observed with Telisotuzumab-Vedotin (c-MET target) and Patritumab-Deruxtecan (Her-3 target), respectively. No cases of ILD have been reported with Sacituzumab-Govitecan (TROP-2 target) or Tusamitamab-Ravtansine (CEACAM5 target).

PERSPECTIVES:

Several risk factors for ADC-induced ILD seem to emerge, including respiratory comorbidities, renal insufficiency, or type and dosage of ADC. Current studies are focusing on the combination of ADC and immunotherapy, although there are few data now available on pulmonary toxicity profiles.

CONCLUSION:

Among the many ADCs being developed, several can cause ILD of varying grades and intensity. Knowledge of their risks, diagnostic and therapeutic modalities is required in order to quickly detect and treat ADC-induced ILD.

01 Jan 2025·Current medicinal chemistry

Review

Author: Ding, Ke ; Zhang, Jinwei ; Trinder, Amelia

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered “undruggable” due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

15 Apr 2024·Clinical cancer research : an official journal of the American Association for Cancer Research

Article

Author: Brister, Eileen ; Reizine, Natalie M. ; Weinfeld, Michael S. ; Kregel, Steven ; Wu, Yaqi ; Kirkpatrick, Brenna J. ; Sverdlov, Maria ; Liu, Li ; Xu, Ziqiao ; Morales, Mathias ; Nonn, Larisa ; Brown, Ryan M. ; Vander Griend, Donald J. ; Nguyen, Ryan H. ; Maienschein-Cline, Mark ; Vellky, Jordan E. ; Gutgesell, Lisa C. ; Notardonato, Lucia D.

Abstract:

Purpose::

Despite successful clinical management of castration-sensitive prostate cancer (CSPC), the 5-year survival rate for men with castration-resistant prostate cancer is only 32%. Combination treatment strategies to prevent disease recurrence are increasing, albeit in biomarker-unselected patients. Identifying a biomarker in CSPC to stratify patients who will progress on standard-of-care therapy could guide therapeutic strategies.

Experimental Design::

Targeted deep sequencing was performed for the University of Illinois (UI) cohort (n = 30), and immunostaining was performed on a patient tissue microarray (n = 149). Bioinformatic analyses identified pathways associated with biomarker overexpression (OE) in the UI cohort, consolidated RNA sequencing samples accessed from Database of Genotypes and Phenotypes (n = 664), and GSE209954 (n = 68). Neutralizing antibody patritumab and ectopic HER3 OE were utilized for functional mechanistic experiments.

Results::

We identified ERBB3 OE in diverse patient populations with CSPC, where it was associated with advanced disease at diagnosis. Bioinformatic analyses showed a positive correlation between ERBB3 expression and the androgen response pathway despite low dihydrotestosterone and stable expression of androgen receptor (AR) transcript in Black/African American men. At the protein level, HER3 expression was negatively correlated with intraprostatic androgen in Black/African American men. Mechanistically, HER3 promoted enzalutamide resistance in prostate cancer cell line models and HER3-targeted therapy resensitized therapy-resistant prostate cancer cell lines to enzalutamide.

Conclusions::

In diverse patient populations with CSPC, ERBB3 OE was associated with high AR signaling despite low intraprostatic androgen. Mechanistic studies demonstrated a direct link between HER3 and enzalutamide resistance. ERBB3 OE as a biomarker could thus stratify patients for intensification of therapy in castration-sensitive disease, including targeting HER3 directly to improve sensitivity to AR-targeted therapies.

136

News (Medical) associated with Patritumab

31 May 2025

·pipelinereview.com

ENHERTU® Reduced the Risk of Death by 30% Versus Ramucirumab Plus Paclitaxel as a Second-Line Therapy in Patients with HER2 Positive Unresectable or Metastatic Gastric Cancer in DESTINY-Gastric04 Phase 3 Trial

TOKYO, Japan & BASKING RIDGE, NJ, USA I May 31, 2025 I Positive results from the DESTINY-Gastric04 phase 3 trial showed ENHERTU ® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to ramucirumab plus paclitaxel in patients with second-line HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Results will be presented today as a late-breaking oral presentation ( LBA #4002 ) at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting and simultaneously published in The New England Journal of Medicine . ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). In the primary endpoint analysis of OS, ENHERTU reduced the risk of death by 30% versus ramucirumab plus paclitaxel (hazard ratio [HR]: 0.70; confidence interval [CI]: 0.55-0.90; p=0.0044). Median OS was 14.7 months with ENHERTU (n=246) versus 11.4 months with ramucirumab plus paclitaxel (n=248). In the secondary endpoint analysis of progression-free survival (PFS), ENHERTU demonstrated a 26% reduction in the risk of disease progression or death versus ramucirumab plus paclitaxel (HR: 0.74; 95% CI: 0.59-0.92; p=0.0074) as assessed by investigator. Median PFS was 6.7 months with ENHERTU versus 5.6 months with ramucirumab plus paclitaxel. A confirmed objective response rate (ORR) of 44.3% (95% CI: 37.8-50.9) was seen in patients treated with ENHERTU with seven complete responses (CR) and 97 partial responses (PR) versus an ORR of 29.1% (95% CI: 23.4-35.3) with three CRs and 66 PRs in the ramucirumab plus paclitaxel arm (p=0.0006). Median duration of response (DOR) was 7.4 months (95% CI: 5.7-10.1) in the ENHERTU arm and 5.3 months (95% CI: 4.1-5.7) in the ramucirumab plus paclitaxel arm. Disease control rate (DCR) was 91.9% (95% CI: 87.7-95.1) with ENHERTU versus 75.9% (95% CI: 70.0-81.2) with ramucirumab plus paclitaxel. Improvements in OS and PFS with ENHERTU were consistent across subgroups. “Gastric cancer is particularly challenging to treat, especially in the advanced stages where the five-year survival rate remains low,” said Kohei Shitara, MD, Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan and lead investigator in the DESTINY-Gastric04 trial. “The superior overall survival demonstrated in DESTINY-Gastric04 confirms that ENHERTU could become the global standard of care in the second-line metastatic setting of HER2 positive gastric cancer or gastroesophageal junction cancer.” The safety profile of ENHERTU in DESTINY-Gastric04 was consistent with previous gastric cancer clinical trials with no new safety concerns identified. The most common grade 3 or higher treatment related adverse events occurring in patients treated with ENHERTU were neutropenia (28.7%), anemia (13.9%), thrombocytopenia (8.6%), leukopenia (7.4%) and fatigue (7.0%). Interstitial lung disease (ILD) or pneumonitis occurred in 13.9% of patients treated with ENHERTU and 1.3% treated in the ramucirumab plus paclitaxel arm. In the ENHERTU arm, the majority of ILD or pneumonitis events were low grade (grade 1 [n=7; 2.9%] or grade 2 [n=26; 10.7%]) except for one grade 3 ILD event (0.4%) as determined by an independent adjudication committee. In the ramucirumab plus paclitaxel arm, there were two grade 3 (0.9%) and one grade 5 (0.4%) ILD events. “ENHERTU continues to deliver impressive results with these new data from DESTINY-Gastric04, which represent the first time a HER2 directed medicine has demonstrated a survival benefit in a randomized phase 3 trial in the second-line HER2 positive metastatic gastric cancer setting,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “Similar to our strategy in other tumor types, we continue to pursue the development of ENHERTU in earlier stages of gastric cancer and have recently initiated phase 3 trials evaluating ENHERTU as part of a combination regimen as a first-line treatment in patients HER2 positive metastatic disease.” “Patients with HER2 positive metastatic gastric cancer who experience progression after first-line treatment have historically faced poor outcomes,” said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. “These results showed that ENHERTU reduced the risk of death by nearly one-third in patients with previously treated HER2 positive metastatic gastric cancer, reinforcing the benefit of ENHERTU in this setting.” ENHERTU is currently approved in more than 70 countries in the second-line or third-line metastatic setting of HER2 positive gastric cancer based on DESTINY-Gastric01 , a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06 , two single-arm phase 2 trials. Daiichi Sankyo and AstraZeneca are currently evaluating ENHERTU in the first-line metastatic setting through the DESTINY-Gastric05 and ARETEMIDE-Gastric01 phase 3 trials. The majority of patients in the DESTINY-Gastric04 trial had received no prior treatment with an immune checkpoint inhibitor (84.1% in the ENHERTU arm and 84.7% in the ramucirumab plus paclitaxel arm) and had two or more metastatic sites (70.3% in the ENHERTU arm and 69.8% in the ramucirumab plus paclitaxel arm). Median duration of follow-up was 16.8 months in the ENHERTU arm and 14.4 months in the ramucirumab plus paclitaxel arm. Median treatment duration was 5.4 months (range: 0.7-30.3) with ENHERTU and 4.6 months (range: 0.9-34.9) with ramucirumab plus paclitaxel. Of the patients that discontinued treatment from the ramucirumab plus paclitaxel arm, 52 (21.0%) proceeded to receive ENHERTU and 12 (4.8%) disitamab vedotin post-trial. As of the data cut-off of October 24, 2024, 18.9% of patients receiving ENHERTU and 18.5% receiving ramucirumab plus paclitaxel remained on study treatment. Summary of DESTINY-Gastric04 Primary Analysis Results About DESTINY-Gastric04 DESTINY-Gastric04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint is OS. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate and safety. In March 2025, an Independent Data Monitoring Committee recommended unblinding DESTINY-Gastric04 based on the superior efficacy of ENHERTU seen at a planned interim analysis. DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America. For more information about the trial, visit ClinicalTrials.gov . About HER2 Positive Gastric Cancer Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. 1 Approximately one million cases of gastric cancer were diagnosed in 2022. 1 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer. 3 Approximately one in five gastric cancers are considered HER2 positive. 3,4 Prior to the results of the DESTINY-Gastric04 trial of ENHERTU, no other HER2 directed medicine has demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial. 5 About ENHERTU ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that has progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 ( ERBB2 ) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 , DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia, Saudi Arabia, Taiwan, U.K. and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY ® in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where 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. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . SOURCE: Daiichi Sankyo

Clinical ResultPhase 3Drug ApprovalASCOLicense out/in

30 May 2025

·www.fiercepharma.com

Fierce Pharma Asia—Former China FDA head under investigation; Daiichi pulls ADC filing

An anti-graft investigation in China, Daiichi's antibody-drug conjugate setback and a Novartis collaboration made our news this week. China's anti-graft watchdog is investigating Bi Jingquan, the former head of the China Food and Drug Administration. Daiichi Sankyo, along with partner Merck & Co., has pulled an FDA approval filing for an antibody-drug conjugate cancer prospect. Novartis expanded a commercial collaboration with Shanghai Pharma. Plus more.1. China investigating former head of food and drug watchdog (Reuters)Bi Jingjuan, the former head of the China FDA, is under investigation in the country for suspected corruption, the Central Commission for Discipline Inspection announced (Chinese) Thursday. Bi was appointed to the CFDA in 2015 and is credited for the country's efforts to streamline drug approvals. In 2018, the CFDA was renamed the National Medical Products Administration as part of a government overhaul.2. Daiichi, Merck pull HER3-DXd filing at FDA after confirmatory trial misses survival endpointEven though a phase 3 trial for Daiichi Sankyo and Merck & Co.'s patritumab deruxtecan hit its primary endpoint of progression-free survival, the trial failed to show a statistically significant benefit in overall survival. This result prompted the partners to pull a biologics license application for the drug as a potential treatment for certain adults with locally advanced or metastatic EGFR-mutated non-small cell lung cancer. The drug previously suffered an FDA rejection last year.3. Novartis expands strategic collaboration with Shanghai Pharma in China to cover eye drugsAs Novartis works to become a top 3 multinational drugmaker in China by sales, the company has enlisted Shanghai Pharma to grow the reach of certain drugs for ocular infections and glaucoma. Last year, Novartis signed on Shanghai Pharma to help build a local supply chain for radioligand therapies. As for Shanghai Pharma, the company is one of the largest pharma distributors and contract sales organizations (CSOs) in the country. Its CSO unit managed 65 drugs last year, contributing around 8 billion Chinese yuan ($1.1 billion) toward those medicines' global sales.4. Drugmakers, trade groups and others voice concerns with pharma-specific tariffsAs the Trump administration weighs sector-specific tariffs with a Section 232 investigation into pharmaceuticals, the Chinese government and the China Chamber of Commerce for Import & Export of Medicines & Health Products offered their thoughts during the public comment process. In its comment, the Chinese government asserted that since 2017, the U.S. has "continuously extended the concept of ‘national security,’ using it as a pretext to launch Section 232 investigations to impose trade protectionist measures" in various industries. Besides the Chinese government, several other entities opposed potential pharma-specific tariffs.5. Sanofi eyes vaccine manufacturing in Vietnam amid tech transfer with local firmSanofi has initiated a tech transfer process with the Vietnam Vaccine Company (VNVC) with the goal to eventually produce certain Sanofi vaccines in the country. As part of the collaboration, Sanofi will also help the VNVC with human resources training and quality management linked to vaccine research and production. Besides the Sanofi project, the VNVC revealed that it will be building a new 26,000-square-meter (279,862-square-foot) production facility in the Long An province in Vietnam.Other News of Note:6. Biotech incubated by TCG Labs inks $210M deal for EpimAb's T-cell engager7. AACE Pharma slammed with FDA warning letter for contract manufacturer's shortfalls

Phase 3Vaccine

30 May 2025

·pipelinereview.com

Patritumab Deruxtecan Biologics License Application for Patients with Previously Treated Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer Voluntarily Withdrawn

BASKING RIDGE, NJ & RAHWAY, NJ. USA I May 29, 2025 I The Biologics License Application (BLA) seeking accelerated approval in the U.S. for Daiichi Sankyo (TSE: 4568) and Merck’s (NYSE: MRK), known as MSD outside of the United States and Canada, patritumab deruxtecan (HER3-DXd) based on the HERTHENA-Lung01 phase 2 trial for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies has been voluntarily withdrawn. The decision to withdraw the BLA is based on topline overall survival (OS) results from the confirmatory HERTHENA-Lung02 phase 3 trial where OS did not meet statistical significance as well as discussions with the U.S. Food and Drug Administration. The decision is unrelated to the Complete Response Letter that was received in June 2024 and outlined findings pertaining to an inspection of a third-party manufacturing facility. Patritumab deruxtecan is a specifically engineered HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck. Results from the HERTHENA-Lung02 phase 3 trial, including previously reported statistically significant progression-free survival (PFS) along with topline OS results, will be presented during an oral presentation (# 8506 ) at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting on Sunday, June 1, 2025. HERTHENA-Lung02 is evaluating patritumab deruxtecan monotherapy versus doublet chemotherapy, consisting of platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy, in patients with EGFR-mutated (exon 19 deletion or L858R mutated) advanced NSCLC after disease progression with a third generation EGFR tyrosine kinase inhibitor (TKI) treatment. Patients achieving tumor response will continue to receive patritumab deruxtecan or chemotherapy until disease progression, per investigator assessment. “EGFR-mutated non-small cell lung cancer has proven to be difficult-to-treat in the second-line metastatic setting and beyond,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “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,” said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. “We would like to thank the patients, their families and investigators for their participation in this study.” 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. 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 a separate phase 1 trial assessing the doses in a similar patient population. The primary endpoint of HERTHENA-Lung01 was objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints included duration of response, PFS, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, OS, safety and tolerability. The ORR data and additional results for key secondary endpoints of HERTHENA-Lung01 were published in the Journal of Clinical Oncology in September 2023. HERTHENA-Lung01 enrolled 277 patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov . About HERTHENA-Lung02 HERTHENA-Lung02 is a global, multicenter, open-label, phase 3 trial evaluating the efficacy and safety of patritumab deruxtecan (5.6 mg/kg every three weeks) monotherapy versus four cycles of doublet chemotherapy (pemetrexed and platinum chemotherapy) in patients with metastatic or locally advanced NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) after failure of third-generation (e.g., osimertinib, lazertinib, aumolertinib, alflutinib) EGFR TKI therapy. Patients in the chemotherapy arm without disease progression after four cycles of pemetrexed and platinum chemotherapy are able to continue treatment with maintenance pemetrexed with no restriction on the number of cycles. The primary endpoint of HERTHENA-Lung02 is PFS as assessed by BICR. Secondary endpoints included OS, ORR, duration of response, clinical benefit rate, time to response, disease control rate, and safety. Patients enrolled in the study underwent brain imaging to allow for assessment of intracranial endpoints, including intracranial PFS as assessed by BICR. HERTHENA-Lung02 enrolled 586 patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov . About EGFR-Mutated Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. Lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. 1 NSCLC accounts for about 87% of all lung cancers. 2 Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation. 3,4 NSCLC is diagnosed at an advanced stage in up to 70% of patients. 5 For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting includes EGFR-directed therapy with or without platinum-based chemotherapy. 6 While these therapies have improved outcomes, most patients eventually experience disease progression and receive subsequent therapies. 7-10 About HER3 HER3 is a member of the HER family of receptor tyrosine kinases. 11 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment. 12 HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival. 13,14 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. About the Patritumab Deruxtecan Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of patritumab deruxtecan across multiple cancers. Trials in combination with other anticancer treatments also are underway. About the Daiichi Sankyo and Merck Collaboration Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024 , the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for gocatamig. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where 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. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com . 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 Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Daiichi Sankyo

ASCOClinical ResultPhase 3Phase 2License out/in

100 Deals associated with Patritumab

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 3	United States	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Belgium	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Canada	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Czechia	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Germany	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Hungary	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Italy	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Poland	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	Spain	Daiichi Sankyo Co., Ltd.	01 Mar 2014
metastatic non-small cell lung cancer	Phase 3	United Kingdom	Daiichi Sankyo Co., Ltd.	01 Mar 2014

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01211483 (HERALD, CTgov)	Phase 1/2	Advanced Lung Non-Small Cell Carcinoma	222	Erlotinib+U3-1287 (Phase 2: U3-1287 18 mg/kg + Erlotinib)	qruvoawfan(rvrhqkspzf) = qgwhbkpydv akvflcbwvr (uhlrvqxfih, aechrvddaw - ujifadlgtq) View more	-	16 Jun 2021
				Erlotinib+U3-1287 (Phase 2: U3-1287 9 mg/kg + Erlotinib)	qruvoawfan(rvrhqkspzf) = tivqfszdor akvflcbwvr (uhlrvqxfih, ghljexatmo - pnnjdvfkwq) View more
NCT02350712 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Squamous Cell Carcinoma of Head and Neck First line	15	Cetuximab+cisplatin+carboplatin+Patritumab	ftlvxeidzi(joviwlraor) = waloehlayj rcmzarhvcx (uriuoiujkr ) View more	Positive	15 Jan 2019
NCT02633800 (CTgov)	Phase 2	Squamous cell carcinoma of head and neck metastatic	87	Cetuximab+Patritumab+Carboplatin+Cisplatin (Patritumab)	ychdsvbpaw(vbgnuqtpem) = fjzxgwliwg jtxrpdaxbc (nbucntdfgj, nsxdqvonnt - uhyezmdeuv) View more	-	07 Jan 2019
				Placebo+Cetuximab+Carboplatin+Cisplatin (Placebo)	ychdsvbpaw(vbgnuqtpem) = qgrzarlcux jtxrpdaxbc (nbucntdfgj, frodjhkjnf - bijolpnaci) View more
NCT02134015 (HER3-Lung, CTgov)	Phase 3	metastatic non-small cell lung cancer	145	Placebo+Erlotinib (Placebo + Erlotinib)	hrsdwvmajj = holmqnahyl anifwshobk (qflxmwcihn, ssgdqkibqd - lzxcufqxql) View more	-	23 Jan 2018
				Erlotinib+Patritumab (Patritumab + Erlotinib)	hrsdwvmajj = tlvfmkysol anifwshobk (qflxmwcihn, fuivdcwdig - iepsuqrjkt) View more
NCT01211483 (HERALD, ASCO2016)	Phase 2	Non-Small Cell Lung Cancer	212	Patritumab + Erlotinib	ldmcourqtu(fcyjaevbkd): HR = 0.41 (95% CI, 0.18 - 0.9), P-Value = 0.02	Positive	20 May 2016
				Placebo + Erlotinib
NCT01211483 (ASCO2014)	Phase 1/2	Advanced Lung Non-Small Cell Carcinoma	145	Patritumab 18 mg/kg every three weeks	erapcwpqnp(diczuiliya) = rrotljpjic ktvcevbnlq (eehxsosylc ) View more	-	20 May 2014
				Patritumab 9 mg/kg every three weeks	erapcwpqnp(diczuiliya) = kmwxoatuwu ktvcevbnlq (eehxsosylc ) View more
NCT01211483 (HERALD, ASCO2014)	Phase 2	Non-Small Cell Lung Cancer	215	High Dose Patritumab	wllrowlyfl(mlnifijphn) = yurvjwtvmn zfudvasddw (lawcxhqprn )	-	20 May 2014
				Low Dose Patritumab	wllrowlyfl(mlnifijphn) = nfztxlnigt zfudvasddw (lawcxhqprn )

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