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

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

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

Health-related quality of life outcomes in SOLTI VALENTINE: A trial of neoadjuvant HER3-DXd +/- letrozole for high-risk hormone receptor positive/HER2-negative early breast cancer (ESMO-BC 2025) - P2 | "HER3-DXd is associated with similar QoL outcomes to standard multi-agent CT. Together with the efficacy and safety results, QoL data provide further support for the continued investigation of HER3-DXd in hormone receptor positive/HER2-negative breast cancer."

Clinical • HEOR • 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 • ERBB3 • HER-2

Patritumab deruxtecan: Primary PFS data from P3 HERTHENA-Lung02 trial (NCT05338970) 2L EGFR mutated NSCLC at ASCO (May 30-Jun 03, 2025) (Daiichi Sankyo) - FY2024 Results

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

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

CS2011: A novel bispecific antibody targeting EGFR and HER3 that demonstrates promising antitumor activity in preclinical evaluation (AACR 2025) - "Approved anti-EGFR therapies, including cetuximab, pantitumumab, and necitumumab, are widely used in treating the aforementioned malignancies. Amivantamab, a bispecific antibody targeting EGFR and c-MET, has been approved for treating advanced NSCLC with EGFR mutations...Daiichi's HER3-ADC, U3-1402, has shown promising clinical results in advanced EGFR-mutant NSCLC, confirming HER3 as a valid therapeutic target... CS2011 is a promising bispecific antibody for the treatment of various advanced solid tumors. Current preclinical data support further IND-enabling development and clinical research on CS2011."

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 • EGFR • ERBB3 • MET • NRG1

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

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

Evolving treatment for advanced Non-small cell lung cancer harbouring common EGFR activating mutations. (PubMed, Crit Rev Oncol Hematol) - "Efforts to extend disease control have led to various upfront intensification strategies, including combining EGFR TKIs with antiangiogenics or chemotherapy (e.g., the FLAURA-2 trial), and pairing novel bispecific antibodies such as amivantamab with third-generation TKIs...Emerging therapies targeting MET amplification (e.g., savolitinib plus osimertinib), leveraging antibody-drug conjugates (e.g., patritumab deruxtecan), or adding immunotherapy and antiangiogenics have shown preliminary promise in overcoming resistance...Ultimately, the evolving landscape of EGFR-mutant NSCLC underscores the need for refined biomarker-driven approaches and personalized regimens to achieve further gains in survival. In this review, we discuss these strategies in detail, highlighting current evidence and future directions for EGFR-mutant NSCLC treatment."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A) (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Feb 2039 ➔ Feb 2032 | Trial primary completion date: Feb 2039 ➔ Feb 2032

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

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 | "Clinical Trial Registration Number: NCT05865990 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

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 | "Clinical Trial Registration Number: NCT04165070 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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 | "Clinical Trial Registration Number: NCT05338970 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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 | "Clinical Trial Registration Number: NCT06797635 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

Preclinical discovery and characterization of EO-1022, a site-specific glycan-conjugated anti-HER3 vc-MMAE ADC for treating solid tumors (AACR 2025) - "EO-1022 is comprised of the highly selective and clinically validated HER3 antibody, seribantumab, that is site-specifically glycan-conjugated with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload to give a drug-to-antibody ratio (DAR) of 4. EO-1022 was evaluated in vitro and in vivo, with patritumab deruxtecan (patri-DXd) as a comparator. EO-1022 demonstrated target-dependent in vitro cytotoxicity and in vivo anti-tumor activity in a HER3-expressing breast cancer CDX model. Additional results on the optimization and characterization of EO-1022 will be presented, including bystander effect assays and in vivo models of HER3-positive breast cancer and EGFR mutant NSCLC. Results from preclinical studies highlight the therapeutic potential of EO-1022 for patients living with HER3-expressing cancers."

Late-breaking abstract • Preclinical • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Beyond HER2 & TROP2: New Targets and Strategic Advances (GBCC 2025) - "Patritumab deruxtecan, the novel anti-HER3 monoclonal antibody-containing ADC, has been investigated in a Phase II single arm study...Other ADCs targeting newer proteins are in earlier studies. A particular focus will be placed on next-generation antibody-drug conjugates (ADCs), bispecific ADCs as innovative approaches to overcoming therapeutic resistance."

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 • CD276 • CEACAM5 • HER-2 • ROR1

Nursing best practices and adverse event management for patients receiving patritumab deruxtecan (HER3-DXd) in the HERTHENA-Lung01 study (ONS 2025) - "Discussion Nurses/NPs, as part of the multidisciplinary team, play a critical role in the management of patients' AEs. Through education, counseling, and provision of care where appropriate, nurses/NPs were able to manage patient expectations, enhance knowledge, and assist in home management of significant AEs, contributing to an optimal patient experience while receiving treatment with HER3-DXd."

Adverse events • Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3

Secretory EMT fuels ERBB3 axis activation in resistance to EGFR inhibitors (AACR 2025) - "Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations, such as exon 19 deletions (del746-750) and the L858R point mutation in exon 21, respond well to third-generation tyrosine kinase inhibitors (TKIs) like osimertinib...Clinical evidence has demonstrated the therapeutic potential of targeting HER3, notably with antibody-drug conjugates (ADCs) like patritumab deruxtecan...Notably, our preclinical models demonstrated that the combination of an NRG1-neutralizing antibody with a dual EGFR blockade—achieved through a TKI and an anti-EGFR antibody—completely eradicated tumors in vivo. These results highlight the critical role of HER3 signaling and its interplay with the tumor microenvironment in mediating TKI resistance and suggest a compelling therapeutic strategy for overcoming resistance in NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ERBB3 • NRG1

Antitumor effect and underlying mechanism on DNA damage response in breast cancer cells treated with HER3-DXd (AACR 2025) - "HER3-DXd is an antibody-drug conjugate (ADC) that combines patritumab, an anti-HER3 antibody and DXd, a topoisomerase I inhibitor, which is linked via a peptide-cleavable linker. HER3-DXd induces DNA damage, apoptotic cell death, and micronuclei formation in sensitive breast cancer cells, but not in insensitive cells. Thus, the induction of DNA damage, rather than protein expression levels of HER3 or internalization rates of HER3-DXd, may be associated with sensitivity to HER3-DXd in these cell lines, suggesting the payload could be particularly important for HER3-DXd activity in these models."

Late-breaking abstract • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • CASP3 • ERBB3 • H2AX • HER-2

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 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1/2 trial • Oncology • Pediatrics • Solid Tumor

A novel dual-payload HER3-directed antibody-drug conjugate, shows potent antitumor efficacy in HER3-low in vivo tumor models (AACR 2025) - "To date, patritumab deruxtecan (U3-1402) is the only HER3-targeting therapy that has demonstrated clinical efficacy in both non-small cell lung cancer. The non-GLP toxicity study in cynomolgus monkeys provided evidence of the favorable safety profile of KHN922, the highest non-severely toxic dose (HNSTD) is 50 mg/kg/dose.In summary, KHN922, an ADC with dual toxins and unique mechanisms of action, displayed superior anti-tumor effects, the ability to overcome treatment-resistance and tumour recurrences, and an acceptable safety profile in preclinical studies. These findings support the potential of KHN922 as a promising advanced therapeutic candidate for HER3 tumors."

Preclinical • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ERBB3

SDP01873, a novel HER3×c-Met bispecific antibody-drug conjugate (ADC) targeting EGFR tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and beyond (AACR 2025) - "SDP01873 showed higher internalization activity than the HER3 ADC, U3-1402 analog (synthesized in-house), indicating an augment to internalization activity through dual targeting. SDP01873 represents a novel HER3×c-Met ADC with superior internalization activity and higher anti-tumor activity in preclinical models of NSCLC and CRC, and efficacy in PDX models resistant to EGFR TKI was also observed. The promising preclinical data support its advancing into clinical testing, and an Investigational New Drug (IND) application to NMPA has been approved in 2024."

Late-breaking abstract • Colorectal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ERBB3 • MET

Efficacy, Safety, and Biomarker Analysis of ICARUS-BREAST01: A Phase 2 Study of Patritumab Deruxtecan (HER3-DXd) in Patients With HR+/HER2– Advanced Breast Cancer (MBCC 2025) - P2 | "Conclusion HER3-DXd showed clinically meaningful activity and a manageable safety profile in patients with HR+/HER2− advanced breast cancer that progressed after ˚2 lines of therapy. Further studies are warranted to confirm the role of HER3-DXd in this setting."

Biomarker • Clinical • Metastases • P2 data • Breast Cancer • Fatigue • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ERBB3 • HER-2

Exposure-Response Relationships in Patients with Non-Small-Cell Lung Cancer and Other Solid Tumors Treated with Patritumab Deruxtecan (HER3-DXd). (PubMed, Clin Pharmacol Ther) - "This observation was supported by low predicted rates of adjudicated drug-related ILD and adverse events leading to treatment discontinuation with the 5.6 mg/kg Q3W regimen. Overall, these results support the selection of HER3-DXd 5.6 mg/kg Q3W as the recommended dosing regimen for patients with NSCLC, and these data inform the optimal dosing regimen for other tumor types."

Journal • Breast Cancer • Colorectal Cancer • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ERBB3 • HER-2

Standard of care of EGFR mutated metastatic NSCLC in first treatment and beyond progression (PubMed, Bull Cancer) - "The combination of TKI/chemotherapy (osimertinib/carboplatine-pemetrexed) and TKI/bispecific antibodies (e.g., amivantamab/lazertinib) are alternatives under evaluation, with benefits in PFS but increased toxicity. Other emerging approaches include conjugated antibodies (patritumab deruxtecan, datopotamab deruxtecan) and next-generation TKIs. In the future, personalized treatment based on the molecular profile and early response to TKIs could optimize management, particularly by integrating predictive markers such as EGFR clearance under treatment."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR