Portrazza (necitumumab) / Eli Lilly, Nippon Kayaku - LARVOL DELTA

Antibody therapeutics: A new era for EGFR-mutant NSCLC treatment. (PubMed, Biochim Biophys Acta Rev Cancer) - "We first summarize the mechanisms of monoclonal antibodies directly targeting EGFR, including cetuximab and necitumumab, and discuss their therapeutic limitations...In addition, we review combination strategies integrating EGFR inhibition with antibodies directed against alternative oncogenic pathways or the tumor microenvironment, including anti-angiogenic agents such as bevacizumab...Finally, we explore advanced antibody modalities, including immune-engaging bispecific antibodies and next-generation ADCs. Collectively, antibody-based therapies are reshaping the treatment landscape through diverse mechanisms, offering renewed promise for overcoming resistance and improving outcomes in EGFR-mutant NSCLC."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD24 • CD55 • CD59 • CD73 • EGFR • ERBB3 • HER-2

ORCHARD: Osimertinib + necitumumab in patients (pts) with advanced NSCLC whose disease progressed on first-line (1L) osimertinib (ESMO Asia 2022) - P2 | "Conclusions Osimertinib + necitumumab showed no new safety signals in this population; however, futility criterion was met and recruitment was closed. These results suggest that this combination may not have the requisite clinical activity for further clinical development in this pt population."

Clinical • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

ORCHARD: Osimertinib Plus Necitumumab in Patients With Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer With a Secondary Epidermal Growth Factor Receptor Alteration Whose Disease Had Progressed on First-Line Osimertinib. (PubMed, JCO Precis Oncol) - P2 | "Osimertinib plus necitumumab demonstrated modest clinical benefit, and the overall risk-benefit analysis indicates that further evaluation of the regimen is not warranted in these molecularly defined subsets of osimertinib resistance."

Journal • Cardiovascular • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • EGFR

Osimertinib plus necitumumab in EGFR-mutant NSCLC: Final results from an ETCTN California Cancer Consortium phase I study. (ASCO 2022) - P1 | "Osi/Neci is feasible and tolerable at the RP2D. EGFR ctDNA was detectable at baseline in the majority of pts with decrease in AF on treatment. Osi/Neci was active in select settings of EGFR-TKI resistance, meeting its prespecified efficacy endpoint in T790Mneg PD on 1st/2nd gen TKI as last therapy (ExC A), EGFR ex20ins post-chemo (ExC D) and PD on 1L osimertinib (ExC E)."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A phase II basket study of necitumumab for EGFR amplification–positive metastatic solid tumors: WJOG15021M (ESMO 2025) - "No treatment-related deaths were noted. Conclusions Although the primary endpoint was not met, necitumumab exhibited promising efficacy in patients with ESCC and GC who harbored EGFR amplification in ctDNA just before necitumumab initiation, supporting further therapeutic development in these settings."

Metastases • P2 data • Pan tumor • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Genito-urinary Cancer • Oncology • Small Intestinal Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Urothelial Cancer • EGFR

Establishment and functional characterization of an EGFR-amplified tumoroid from squamous cell carcinoma of unknown primary. (PubMed, Hum Cell) - "Notably, the therapeutic sensitivity observed in the tumoroids was generally consistent with the patient's clinical response to platinum-based chemotherapy combined with necitumumab. These findings demonstrate that a CUP-derived tumoroid can be successfully established while preserving the key molecular and pathological features of the original tumor. This model provides a platform for functional evaluation of therapeutic vulnerabilities and offers proof-of-concept for integrating patient-derived tumoroids into therapeutic decision-making in CUP."

Journal • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Unknown Primary • EGFR

Drug-induced paronychia: a disproportionality and time-to-onset pharmacovigilance study using FAERS and JADER. (PubMed, Cutan Ocul Toxicol) - "The ten drugs with the strongest disproportionality signals (ranked by ROR) were Dacomitinib [ROR 374.77; 95% CI 276.31-508.31], Selumetinib [304.66; 228.55-406.10], Afatinib [296.98; 264.27-333.74], Panitumumab [204.37; 183.10-228.11], Amivantamab [167.61; 124.71-225.26], Necitumumab [151.38; 67.14-341.35], Mobocertinib [117.03; 71.21-192.34], Erdafitinib [59.36; 33.57-104.99], Lapatinib [48.09; 39.71-58.24], and Gefitinib [47.28; 37.09-60.27]...Time-to-onset analysis of 30 drugs with valid TTO data revealed that median onset times ranged from 4 days (Necitumumab) to 575.5 days (Alendronate), with several of the most frequently reported EGFR and MEK inhibitors exhibiting an early-failure pattern (Weibull β < 1), supporting concentrated monitoring during the first weeks of therapy...These findings, derived from spontaneous reporting data, indicate associations rather than causal risk and require further clinical and epidemiologic evaluation. The signals identified may..."

Adverse events • Journal • Oncology • Pain

Efficacy and safety of necitumumab and pembrolizumab combination therapy in advanced non-small-cell lung cancer with ≥50% PD-L1 expression: A nonrandomized phase II trial. (PubMed, Clin Cancer Res) - "The pembrolizumab and necitumumab combination exhibited a promising ORR of 76.0% with a manageable safety profile in patients with NSCLC who had high PD-L1 expression. These findings highlight the need for further research on this regimen for patients with advanced NSCLC who have high PD-L1 expression."

IO biomarker • Journal • P2 data • Cardiovascular • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • PD-L1

Multitask learning of longitudinal circulating biomarkers and clinical outcomes: identification of optimal machine-learning and deep-learning models. (PubMed, BMC Med Inform Decis Mak) - P3 | "In conclusion, we identified that MFPCA-Cox represents a robust and versatile joint modeling algorithm for high-dimensional biomarker longitudinal data with irregular and missing data, capturing complex relationships within the data, yielding accurate predictions for both longitudinal biomarkers and survival outcomes, and gaining insights into the underlying dynamics."

Biomarker • Clinical • Clinical data • Journal • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pharmacovigilance analysis of cutaneous adverse drug reactions for cetuximab, panitumumab, and necitumumab based on EudraVigilance and WHO VigiAccess. (PubMed, Front Pharmacol) - "These findings highlight distinct agent-specific dermatologic toxicity signatures among anti-EGFR monoclonal antibodies and demonstrate the value of real-world pharmacovigilance data in complementing clinical trial evidence. Improved recognition of differential toxicity patterns may support personalized monitoring and management strategies for patients receiving EGFR-targeted therapies."

Adverse drug reaction • Adverse events • Journal • Dermatitis • Dermatology • Immunology • Oncology • Pruritus • Solid Tumor

Durable efficacy of first-line necitumumab plus pembrolizumab in PD-L1–high advanced NSCLC: Final results of the phase II K-TAIL-202 study. (ASCO 2026) - P2 | "At final analysis, first-line necitumumab plus pembrolizumab demonstrated durable antitumor activity and encouraging long-term survival as a chemotherapy-free regimen in patients with PD-L1–high advanced NSCLC. Toxicities were consistent with the known profiles of EGFR-targeted antibodies and PD-1 inhibitor therapy, underscoring the need for careful monitoring. These findings warrant further confirmation in a randomized phase III clinical trial."

Clinical • IO biomarker • Metastases • P2 data • Dermatitis • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Solid Tumor • PD-L1 • TIGIT

Necitumumab plus pembrolizumab and chemotherapy for untreated advanced squamous NSCLC: Phase I/II NEJ048A/NEXUS. (ASCO 2026) - " Patients received necitumumab (400–800 mg on days 1 and 8), pembrolizumab (200 mg on day 1), nab-paclitaxel (100 mg/m² on days 1, 8, and 15), and carboplatin (AUC 5 on day 1) every 3 weeks for four cycles, followed by necitumumab plus pembrolizumab maintenance. The addition of necitumumab to pembrolizumab and platinum-based chemotherapy demonstrated manageable toxicity and resulted in a high ORR in patients with untreated squamous NSCLC. These findings support the potential activity of EGFR blockade–based immunochemotherapy and warrant further clinical investigation."

IO biomarker • Metastases • P1/2 data • Constipation • Dental Disorders • Dermatitis • Gastroenterology • Gastrointestinal Disorder • Immunology • Leukopenia • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • Stomatitis • EGFR

Promotive clinical effects of pembrolizumab with necitumumab in patients having advanced non-small cell lung cancer with PD-L1 expression of 50% or higher in a phase II study (K-TAIL-202) (AACR 2024) - P2 | "However, combination therapies comprising pembrolizumab and ipilimumab, tiragolumab, or lenvatinib have not demonstrated superior efficacy in this patient group. Combination therapy comprising pembrolizumab and necitumumab demonstrated a 76.0% ORR, meeting the primary endpoint, with manageable toxicities. The regimen showed promising clinical activity in patients with NSCLC and high PD-L1 expression, warranting further investigation. Clinical trial ID: jRCT2031200248."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

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...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."

Bispecific • 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

UCLA l-08: Necitumumab and Trastuzumab in Combination With Osimertinib for the Treatment of Refractory Epidermal Growth Factor Receptor (EGFR)-Mutated Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

Mes8 : Designing Future Treatment Strategy for Squamous Cell Lung Cancer - Skillfully Manipulating Necitumumab - (JSMO 2026) - "Sponsored by: Nippon Kayaku Co., Ltd."

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

Effects of N361 Glycosylation on Epidermal Growth Factor Receptor Biological Function. (PubMed, Cancers (Basel)) - "Disruption of glycosylation at N361, located near the ligand binding and dimerization regions, created a dominant negative form of EGFR, which non-productively co-localized with HER2, resulting in a blockage in proliferation. These findings underline the critical relevance of post-translational glycosylation modifications on EGFR function."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

A novel approach for inhibiting the CD16a cleavage and promoting antibody-dependent cellular cytotoxicity against tumors (SITC 2025) - "We discovered that F9H4 synergized with cetuximab and necitumumab to inhibit tumor growth and that activity was associated with CD16a upregulation by blood NK cells, attesting to the inhibition of shedding in vivo.Conclusions F9H4 is a novel approach for prolonging the CD16a native state on the cellular surface to enable engagement by tumor cell-opsonizing antibodies. (B-C) Mice were inoculated subc with LLC1-hEGFR. mAbs were given by ip injections"

IO biomarker • Lung Cancer • Oncology • Solid Tumor • EGFR • FCGR3A

CS-01: a next-generation active immunotherapy that depletes epidermal growth factor in squamous NSCLC (AACR-NCI-EORTC 2025) - "EGFR signaling often drives sqNSCLC, yet broad anti-EGFR monoclonal antibodies (mAbs), necitumumab and cetuximab, provide limited benefit and cause substantial toxicity, underscoring the need for better patient selection...In addition to overcoming its CMC limitations, CS-01 surpasses CIMAvax-EGF in both immunogenicity and potency...Our approach offers key advantages over monoclonal antibody therapies, including reduced resistance, fewer doses, and minimal risk of anti‑drug antibodies (ADA). Given the limited accessibility of monoclonal antibodies in many parts of the world, our platform offers a practical, scalable, cost-effective alternative to chronic mAb therapy across oncology, autoimmune, and infectious diseases."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TGFA

Detection and warning of drug-induced hypomagnesemia: a pharmacovigilance study of the FDA Adverse Event Reporting System. (PubMed, Magnes Res) - "Omeprazole led with 1,556 reports (20.75%), followed by pantoprazole, panitumumab, cetuximab, and esomeprazole. Disproportionality analysis revealed necitumumab as the drug with the strongest signal, followed by capreomycin, panitumumab, pantoprazole, and omeprazole...We issue warnings regarding drugs associated with specific combination therapies that cause adverse reactions leading to hypomagnesemia. Furthermore, to delve deeper into the relationship between drugs and hypomagnesemia, reliance on more credible research in this field is required."

Adverse events • Journal

Final Analysis of Phase Ib/II Study of Osimertinib, Necitumumab and Trastuzumab for Refractory EGFR-Mutated Lung Cancer (IASLC-WCLC 2025) - "Biomarker analysis is underway. Conclusions : Combination osimertinib, necitumumab and trastuzumab toxicities are manageable, and the combination has promising preliminary efficacy in refractory EGFR -mutated metastatic NSCLC."

P1/2 data • Cardiovascular • Hypertension • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR • HER-2

Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor (clinicaltrials.gov) - P1 | N=138 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Jun 2027

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

Skin disorder within 30 days is a favorable prognostic factor in patients with lung squamous cell carcinoma treated with necitumumab plus gemcitabine and cisplatin: a sub-analysis of the NINJA study. (PubMed, Ther Adv Med Oncol) - "Skin disorders are major adverse events associated with necitumumab plus gemcitabine and cisplatin (Neci + GC) administration. A skin disorder within 30 days was a favorable prognostic factor for patients with LSCC administered Neci + GC. Additionally, minocycline administration may be beneficial in patients who develop skin disorders within 30 days."

Biomarker • Journal • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

A Case of EGFR-mutant Squamous Cell Lung Cancer Treated With Necitumumab Combination Therapy. (PubMed, In Vivo) - "The combination therapy of cisplatin, gemcitabine, and necitumumab was effective in treating pretreated EGFR-mutant squamous cell lung cancer in this case. It is necessary to accumulate more evidence to determine the most effective treatment for advanced EGFR-mutant squamous cell lung cancer."

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

A Phase II study of cisplatin and gemcitabine plus necitumumab after immuno-chemotherapy: WJOG14120L NESSIE study (JSMO 2025) - No abstract available

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer