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

Patritumab deruxtecan in HR+HER2- advanced breast cancer: a phase 2 trial. (PubMed, Nat Med) - P2 | "Overall, HER3-DXd showed promising activity and manageable tolerability in patients with HR+HER2- metastatic breast cancer who progressed on CDK4/6 inhibitors. These findings highlight the need for larger trials to define HER3-DXd efficacy relative to other drugs, including antibody-drug conjugates (ClinicalTrials.gov Identifier: NCT04965766 )."

Journal • P2 data • Alopecia • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Immunology • Oncology • Solid Tumor • ER • ERBB3 • HER-2

JS212, a novel bispecific ADC targeting EGFR and HER3, demonstrates superior and broad antitumor activity in preclinical evaluation (AACR 2026) - "JS212 also had better antitumor activity than BL-B01D1 in an osimertinib-resistant HCC827 model. Additionally, JS212 induced near complete regression in either BL-B01D1 or patritumab-deruxtecan resistant SW620 model... JS212 is a promising EGFR and HER3 dual targeting ADC that shows superior and broad-spectrum antitumor activities and a favorable safety and pharmacokinetic profiles in preclinical evaluation, supporting its first-in-human studies. Its phase I clinical trial is ongoing, and results will be reported elsewhere."

ADC • Bispecific • First-in-human • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3

Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06) (clinicaltrials.gov) - P1/2 | N=210 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Dec 2026 ➔ May 2028

Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ERBB3 • HER-2

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=32 | Recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=190 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=32 ➔ 190

Enrollment change • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

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

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=190 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=57 ➔ 190

Enrollment change • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=57 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=32 ➔ 57

Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov) - P1/2 | N=190 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2036 ➔ May 2037

Enrollment open • Trial completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Limited efficacy of HER3-DXd in colorectal cancer PDX models reveals molecular resistance mechanisms and informs rational combinatorial strategies (AACR 2026) - "We evaluated HER3-DXd in a panel of 17 molecularly characterized mCRC patient-derived xenograft (PDX) models, the majority of which were derived from patients previously treated with and resistant to irinotecan. Phospho-proteomic data supported adaptive pathway rewiring following HER3 blockade. These findings highlight the complexity of HER3 signaling in chemotherapy-refractory mCRC and support the development of biomarker-driven combination strategies to enhance therapeutic efficacy of HER3-targeted ADCs (and conceivably other ADCs with topoisomerase inhibitor payload) in this setting."

Clinical • Breast Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3

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

Payload-centric determinants of sustained benefit from HER3-DXd and other TOP1-inhibitor ADCs in breast cancer: A systematic review of clinical, translational and preclinical evidence (ESMO-TAT 2026) - "Integrated evidence indicates HRD/BRCAness, replication stress and R-loop dysfunction, with SLFN11/RB1 contexts, associate with durable HER3-DXd benefit, while heavy prior cytotoxics and payload resistance predict relapse. We recommend RAD51 foci, SLFN11 testing and targeted TOP1 sequencing in clinical trials to inform clinical ADC sequencing strategies."

ADC • Preclinical • Review • Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • ERBB3 • RAD51 • RB1 • SLFN11 • TOP1

Exploring HER3; A potentially targetable biomarker in rare metaplastic breast cancers (Sarcoma-RC 2026) - "This work also highlights a potential treatment strategy for this chemo-refractory rare cancer and supports further investigation of HER3-targeting antibodies (such as Patritumab-deruxtecan) with or without checkpoint blockade for mTNBC...Legal entity responsible for the study Nour Abuhadra. Funding Has not received any funding."

Biomarker • IO biomarker • Tumor mutational burden • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ERBB3 • KMT2C • PD-L1 • PIK3CA • PTEN • RB1 • TERT • TMB • TP53

HERTHENA-PanTumor01 (NCT06172478): Expansion of a Global Phase 2 Trial of HER3-DXd in Patients With Advanced/Metastatic HR+/HER2− Breast Cancer (MBCC 2026) - P2 | No abstract available

Clinical • Metastases • P2 data • Pan tumor • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

A MODULAR ONCOLOGY REFERENCE MODEL FOR EARLY ECONOMIC EVALUATION: A CASE STUDY IN EGFR-MUTATED NSCLC (ISPOR 2026) - P2 | "Our analysis illustrated that combining reusable model structures with indication-specific early phase trial inputs, real-world ECA and architecture designed for future AI-assisted automation enables a reference model platform for timely, high-quality decision support for oncology assets in early stage."

Case study • Clinical • HEOR • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • ERBB3

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=312 | Active, not recruiting | Sponsor: Daiichi Sankyo | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Oct 2017 ➔ Feb 2020

Enrollment open • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=309 | Recruiting | Sponsor: Daiichi Sankyo | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Jan 2022 ➔ Mar 2026

Enrollment open • Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=271 | Active, not recruiting | Sponsor: Daiichi Sankyo, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=271 | Active, not recruiting | Sponsor: Daiichi Sankyo, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=264 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=216 | Active, not recruiting | Sponsor: Daiichi Sankyo, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=63 | Not yet recruiting | Sponsor: Daiichi Sankyo, Inc.

New P1 trial • Lung Adenocarcinoma • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Thoracic Cancer • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=198 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | N=130 ➔ 198

Enrollment change • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • ROS1

U31402-A-U102: U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Daiichi Sankyo, Inc. | N=63 ➔ 130 | Trial completion date: Feb 2020 ➔ Oct 2023 | Trial primary completion date: Feb 2020 ➔ Oct 2021

Enrollment change • Trial completion date • Trial primary completion date • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • ROS1