patritumab deruxtecan (U3-1402) / Daiichi Sankyo, Merck (MSD) - LARVOL DELTA

U31402-A-U103: HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=246 | Active, not recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Feb 2026 ➔ Apr 2027 | Trial primary completion date: Jun 2025 ➔ Jan 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non-Small Cell Lung Cancer After Platinum-Based Chemotherapy and Immunotherapy. (PubMed, J Clin Oncol) - "The previously reported efficacy and safety of HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC are also observed in those with other NSCLC subtypes and warrant further clinical evaluation."

IO biomarker • Journal • Interstitial Lung Disease • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • ERBB3

PARAMETer: A Window of Opportunity Study of Patritumab Deruxtecan in Patients With Brain Metastases (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Mustafa Khasraw, MBChB, MD, FRCP, FRACP | N=15 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Cholangiocarcinoma • Oncology • Solid Tumor • ERBB3 • HER-2 • PGR

A Study of Patritumab Deruxtecan in Pediatric Participants With Relapsed or Refractory Solid Tumors (MK-9999-01C/LIGHTBEAM-U01) (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Pediatrics • Solid Tumor

Multimodal cancer therapy consisting of antibody-drug conjugates and radiotherapy in cancer treatment (AACR 2025) - "Accordingly, combination of RT with ADCs targeting HER2: trastuzumab emtansine/deruxtecan/duocarmazine (T-DM1/T-DXd/T-Duo) and disitamab vedotin, TROP2: datopotamab deruxtecan and sacituzumab govitecan, EGFR: depatuxizumab MMAE, HER3: patritumab deruxtecan, Nectin4: enfortumab vedotin and CEACAM5: tusamitamab ravtansine were evaluated. Together, this study demonstrates that inherent sensitivity of tumor cells to different payload classes, DAR and TAA dynamic are of relevance for the efficacy of ADC. Informed selection of ADC exhibited synergistic effects with RT providing a novel multimodal and promising strategy for efficient cancer eradication."

Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • CEACAM5 • EGFR • ERBB3 • HER-2 • NECTIN4

Patritumab deruxtecan (HER3-DXd) in active brain metastases (BM) from metastatic breast (mBC) and non–small cell lung cancers (aNSCLC), and leptomeningeal disease (LMD) from advanced solid tumors: Results from the TUXEDO-3 phase II trial. (ASCO 2025) - P2 | "TUXEDO-3 is the first trial evaluating efficacy and safety of HER3-DXd in pts with BM or LMD. HER3-DXd showed substantial CNS activity in parenchymal metastases and LMD, and may be a potential novel treatment for CNS disease in cancer pts."

Metastases • P2 data • CNS Disorders • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

Patritumab deruxtecan: "Primary analysis of the HERTHENA-Lung02 study demonstrated a statistically significant improvement in PFS for HER3-DXd vs PBC in patients with EGFR-mutated NSCLC that progressed on thirdgeneration TKI therapy (HR 0.77, p=0.011)"; Non small cell lung cancer (Daiichi Sankyo) - ASCO 2025

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

KEYMAKER-U01 substudy 01A: Phase 1/2 study of pembrolizumab plus ifinatamab deruxtecan (I-DXd) or patritumab deruxtecan (HER3-DXd) with or without chemotherapy in untreated stage IV non–small-cell lung cancer. (ASCO 2025) - P1/2 | "KEYMAKER-U01 substudy 01A (NCT04165070) is a phase 1/2, two-part, rolling arm, open-label study assessing the efficacy and safety of pembrolizumab plus an investigational agent (part A: vibostolimab, boserolimab, MK-4830, and MK-0482; part B: I-DXd and HER3-DXd), with or without chemotherapy in untreated stage IV NSCLC...In Arms 5 and 6, participants will receive I-DXd plus pembrolizumab 200 mg Q3W (Arm 5) or I-DXd plus pembrolizumab with 4 cycles of carboplatin area under the curve 5 or 6 mg/ml/min (Arm 6); I-DXd dose will be at 8mg/kg...The primary endpoint is incidence of dose-limiting toxicities until the start of cycle 2, and AEs and treatment discontinuations due to AEs until 40 days after last treatment (90 days for serious AEs); secondary endpoints include ORR and DOR, both per RECIST v1.1 by BICR, and pharmacokinetic parameters, including maximum concentration (Cmax) and maximum trough concentration (Ctrough) of I-DXd and HER3-DXd. Enrollment will be..."

IO biomarker • Metastases • P1/2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ERBB3 • HER-2 • ROS1

Patritumab deruxtecan (HER3-DXd) in resistant EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) after a third-generation EGFR TKI: The phase 3 HERTHENA-Lung02 study. (ASCO 2025) - P3 | "HER3‑DXd demonstrated statistically significant improvement in PFS vs PBC in pts with EGFRm NSCLC post EGFR TKI therapy. The safety profile was manageable, consistent with prior reports. Most common TEAEs were hematologic and gastrointestinal."

Metastases • P3 data • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • ERBB3

HERTHENA-Breast03: A phase 2, randomized, open-label study evaluating neoadjuvant patritumab deruxtecan + pembrolizumab before or after pembrolizumab + chemotherapy for early-stage TNBC or HR-low+/HER2− breast cancer. (ASCO 2025) - P2 | "There is a need for improved neoadjuvant therapy to increase the rate of pCR, as patients who do not achieve pCR have a high risk of recurrence, and to reduce risk of long-term toxicities associated with cyclophosphamide and anthracyclines...This phase 2 study (NCT06797635) will evaluate neoadjuvant HER3-DXd + pembro before or after carboplatin + paclitaxel + pembro for early-stage TNBC or HR-low+/HER2− breast cancer...Enrollment is ongoing. a200 mg Q3W; bAUC 1.5 mg/mL/min QW; c80 mg/m2 QW; d60 mg/m2 Q3W; e90 mg/m2 Q3W; f600 mg/m2 Q3W."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

TUXEDO-3: A phase 2 trial of patritumab deruxtecan for patients with leptomeningeal metastasis. (PubMed, Neuro Oncol) - No abstract available

Journal • P2 data • Oncology

Patritumab deruxtecan induces immunogenic cell death. (PubMed, Oncoimmunology) - "Tumor-free mice developed immune memory that led to the rejection of syngeneic tumors after rechallenge. In conclusion, patritumab deruxtecan is equipped with a cytotoxic payload that induces hallmarks of ICD in vitro and elicits antitumor immunity in vivo."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CALR • ERBB3 • HMGB1

Diffuse interstitial lung disease induced by antibody-drug conjugates (PubMed, Rev Mal Respir) - "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."

Journal • Review • Interstitial Lung Disease • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Solid Tumor • CEACAM5 • ERBB3 • HER-2 • MET

Efficacy and Safety of Antibody-Drug Conjugates for Lung Cancer Therapy: A Systematic Review of Randomized and Non-Randomized Clinical Trials. (PubMed, Pharmaceutics) - "Five ADCs were evaluated: trastuzumab deruxtecan (T-DXd), trastuzumab emtansine (T-DM1), telisotuzumab vedotin, patritumab deruxtecan, and datopotamab deruxtecan (Dato-DXd)...Dato-DXd demonstrated improved ORR (26.4% vs. 12.8%) and PFS (4.4 vs. 3.7 months) compared to docetaxel...While ADCs offer significant clinical benefits, careful patient selection and proactive management of adverse events remain crucial. Ongoing and future trials will further refine the role of ADCs in personalized NSCLC treatment, potentially expanding their tumor-agnostic use to broader patient populations."

Clinical • IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2 • MET • TACSTD2

HER3-DXd Does Not Yield Improved OS in EGFR-Mutated NSCLC (Cancer Network) - P3 | N=586 | HERTHENA-Lung02 (NCT05338970) | Sponsor: Daiichi Sankyo | "For patients with EGFR mutation–positive locally advanced or metastatic non–small cell lung cancer (NSCLC), patritumab deruxtecan (HER3-DXd) did not elicit improved overall survival (OS), according to results from the phase 3 HERTHENA-Lung02 trial (NCT05338970) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The median OS was 16.0 months (95% CI, 13.7-18.7) in the patritumab deruxtecan arm vs 15.9 months (95% CI, 14.6-17.9) in the chemotherapy arm (HR, 0.98; 95% CI, 0.79-1.22). The median follow-up was 18.7 vs 18.6 months in the 2 arms, respectively....The median progression-free survival (PFS) was 5.8 months with patritumab deruxtecan vs 5.4 months with chemotherapy (HR, 0.77; 95% CI, 0.63-0.94; P =.011). The 9-month probability of PFS was 29% (95% CI, 23%-35%) vs 19% (95% CI, 14%-25%), respectively."

P3 data • Non Small Cell Lung Cancer

Patritumab deruxtecan in leptomeningeal metastatic disease of solid tumors: the phase 2 TUXEDO-3 trial. (PubMed, Nat Med) - P2 | "TUXEDO-3 showed clinically relevant HER3-DXd activity in patients with LMD. ClinicalTrials.gov identifier: NCT05865990 ."

Journal • P2 data • Breast Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Oncology • Pain • Solid Tumor • Thrombocytopenia • ERBB3

PARAMETer: A Window of Opportunity Study of Patritumab Deruxtecan in Patients With Brain Metastases (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Mustafa Khasraw, MBChB, MD, FRCP, FRACP | Not yet recruiting ➔ Recruiting

Enrollment open • Cholangiocarcinoma • Oncology • Solid Tumor • ERBB3 • HER-2 • PGR

Preclinical studies of BR-2302: A HER3xEGFR bi-specific Exd-containing ADC (AACR 2025) - "To combat this issue, novel HER3-targeting therapies are under investigation, including antibody-drug conjugates (ADCs) such as Patritumab Deruxtecan (U3-1402), which have shown encouraging results in clinical trials, underscoring the potential of HER3 targeting to overcome resistance...Izalonatamab brengitecan (BL-B01D1), an ADC designed for simultaneous targeting of EGFR and HER3, has demonstrated substantial clinical benefits in heavily pretreated patients with EGFR-mutant non-small cell lung cancer (NSCLC)...Collectively, our findings indicate that BR-2302 possesses promising anti-tumor properties. This innovative therapeutic approach has the potential to improve treatment outcomes for patients with solid tumors expressing both HER3 and EGFR, warranting further clinical exploration."

Preclinical • Colon Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

Patritumab Deruxtecan Biologics License Application for Patients With Previously Treated Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer Voluntarily Withdrawn (Merck (MSD) Press Release) - "The Biologics License Application (BLA) seeking accelerated approval in the U.S. for Daiichi Sankyo (TSE: 4568) and Merck’s...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."

FDA event • Non Small Cell Lung Cancer

HER3-DXd shows promising results in the phase II TUXEDO-3 study for patients with limited therapeutic options (PRNewswire) - P2 | N=63 | TUXEDO-3 (NCT05865990) | "Leading international medical research company, MEDSIR announced today the positive results of the TUXEDO-3 trial at the American Society of Clinical Oncology (ASCO) Annual Meeting 2025....The TUXEDO-3 study aimed to assess whether HER3-DXd could be an effective treatment option for patients with mBC and aNSCLC with active brain metastases, and leptomeningeal disease from solid tumors. The study met its primary objectives, with 23.8% and 30% patients achieving intracranial responses in active brain metastases from patients with mBC and aNSCLC, respectively, and 65% patients with leptomeningeal disease alive after 3 months. Side effects were consistent with previous studies using HER3-DXd. Tests evaluating quality of life and neurocognitive functions showed that patients remained stable or improved during the treatment follow-up."

P2 data • Breast Cancer • HER2 Positive Breast Cancer • Lung Non-Small Cell Squamous Cancer

Integrated Two-Analyte Population Pharmacokinetics Model of Patritumab Deruxtecan (HER3-DXd) Monotherapy in Patients with Solid Tumors. (PubMed, Clin Pharmacokinet) - "The final integrated population PK model characterized the PK of both anti-HER3-ac-DXd and DXd in patients with solid tumors treated with HER3-DXd and supported the selected 5.6 mg/kg Q3W dosing regimen. Consistent with current data, dose adjustment based on the covariates investigated is not warranted."

Journal • Monotherapy • PK/PD data • Colorectal Cancer • Hepatology • Oncology • Solid Tumor • ERBB3 • HER-2

CS5007: A novel EGFR and HER3 dual-targeted antibody-drug conjugate (ADC) with potent antitumor activity in preclinical studies (AACR 2025) - "For instance, MRG003, an EGFR-targeted ADC, has shown encouraging clinical outcomes in NPC and HNSCC...Daiichi's HER3-ADC, U3-1402, has shown promising clinical results in advanced EGFR-mutant NSCLC, confirming HER3 as a valid therapeutic target for ADC. Additionally, BL-B01D1, an EGFR/HER3 bispecific ADC, has shown encouraging phase 1 data in advanced cancers... CS5007 is a promising dual-targeted ADC that demonstrates potent antitumor efficacy with a favorable safety and PK profile. These preclinical findings support its further IND-enabling studies and clinical investigations for the treatment of various advanced solid tumors."

Preclinical • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ERBB3

Additional Data and Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio at ASCO (Daiichi Sankyo Press Release) - "Oral presentations also will highlight initial results from the TUXEDO-3 phase 2 trial (#2005) evaluating patritumab deruxtecan in patients with metastatic breast cancer or advanced NSCLC and active brain metastases and in patients with leptomeningeal carcinomatosis/disease from advanced solid tumors, as well as results from a phase 1 trial (#10003) evaluating valemetostat, a dual EZH1 and EZH2 inhibitor, in pediatric patients with malignant solid tumors...Additional DXd ADC trials-in-progress poster presentations include the REJOICE-PanTumor01 phase 2 trial (TPS3158) evaluating raludotatug deruxtecan (R-DXd) in patients with locally advanced or metastatic gynecologic or genitourinary cancers, IDeate-PanTumor02 phase 1b/2 trial (TPS3157) evaluating ifinatamab deruxtecan in patients with recurrent or metastatic solid tumors and a substudy of KEYMAKER-U06, a phase 1/2 trial (TPS4209) evaluating ifinatamab deruxtecan in combination with pembrolizumab..."

Clinical data • Trial status • Acute Myelogenous Leukemia • Esophageal Squamous Cell Carcinoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

An evaluation of patritumab deruxtecan for the treatment of EGFR-mutated non-small cell lung cancer. (PubMed, Expert Opin Biol Ther) - "Patients with advanced EGFR-mutant NSCLC who have received TKI therapy and chemotherapy have limited treatment options. Patritumab deruxtecan demonstrates clinical activity in this population with manageable side effects, addressing an unmet need for patients."

Journal • Review • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • ERBB3 • HER-2