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

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

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

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

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

Evening Seminar 22 Revisiting the Treatment Strategies for Squamous Cell Lung Cancer-Positioning of Necitumumab- (JSMO 2025) - "Sponsored by Nippon Kayaku Co.,Ltd."

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

Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study. (PubMed, Ther Adv Med Oncol) - "On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival."

Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

Afatinib and Necitumumab in EGFR-Mutant NSCLC with Acquired Resistance to Tyrosine Kinase Inhibitors. (PubMed, JTO Clin Res Rep) - "Afatinib plus necitumumab was safe but had limited activity in patients with EGFR-mutated NSCLC. Biomarker studies may identify patient subgroups that are more likely to benefit."

Journal • Preclinical • Cardiovascular • Lung Cancer • Mucositis • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Stomatitis • EGFR

A Case of Advanced Biliary Tract Cancer With EGFR Amplification That Responded to Necitumumab. (PubMed, Cancer Rep (Hoboken)) - "This report supports the clinical benefit of anti-EGFR antibodies for EGFR-amplified biliary tract cancers and the importance of genomic analysis in personalized therapy and drug resistance research."

Journal • Metastases • Biliary Cancer • Biliary Tract Cancer • Gallbladder Cancer • Hepatology • Oncology • Solid Tumor • EGFR

Phase I study of afatinib + necitumumab in #JTOCRR for pts with #EGFR NSCLC after previous TKI. No responses and 32% with G3+ AEs. I was optimistic about TKI / mAB combos for #EGFR NSCLC in the past but not enough signal in the resistant setting.

P1 data

Afatinib and Necitumumab in EGFR-Mutant Non-Small Cell Lung Cancer with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors (JTO Clinical and Research Reports) - P1 | N=22 | NCT03054038 | "A total of 22 patients with EGFR-mutated NSCLC were enrolled. The maximum tolerated dose (MTD) was afatinib 40 mg oral daily plus necitumumab 600 mg intravenous on days 1 and 15 every 28 days. There were no Grade 4-5 adverse events observed, and seven patients (32%) experienced Grade 3 treatment-related adverse events (3 rash; 1 each oral mucositis, diarrhea, headache, and ventricular arrhythmia and tachycardia). In the entire cohort, there were no responses observed, the median progression-free survival (PFS) was 1.8 months, and the disease control rate (DCR) was 36% but varied between subgroups."

P1 data • Non Small Cell Lung Cancer

Taking on Acquired Resistance in EGFR-Mutant NSCLC - TKIs are the first-line of defense, but "the more options we have the better," expert says (MedPageToday) - "Velcheti said that more data are needed to fully understand when to continue targeting EGFR and when to switch to other classes of drugs. To that end, the phase II ORCHARD trialopens in a new tab or window will test different agents in combination with osimertinib based on the identified TKI resistance mechanisms. These other agentsopens in a new tab or window include savolitinib, gefitinib (Iressa), Dato-DXd, necitumumab (Portrazza), and other drugs specific to MET alterations, C797X mutations, or no identified biomarker."

Media quote

Transforming Lung Cancer Management: A Promising Case Study of Immune Checkpoint Inhibitor Success Following a Multidisciplinary Approach. (PubMed, Diagnostics (Basel)) - "Two years after initial treatment, cancer relapse led to the administration of nivolumab, which was halted due to the development of drug-induced pneumonitis...Four years after her diagnosis, the patient received a ninth-line therapy combining cisplatin, gemcitabine, and necitumumab, followed by palliative neck radiation due to increasing lymph node size. Remarkable tumor regression occurred three months after introducing atezolizumab as the tenth-line treatment, suggesting that previous treatments, particularly radiotherapy and cisplatin, might have enhanced PD-L1 expression, aligning with the existing literature. This case highlights the urgent need for further research to elucidate the intricate interplay between treatment history and PD-L1 expression in squamous cell carcinoma, emphasizing the importance of accumulating case studies to inform therapeutic strategies."

Checkpoint inhibition • IO biomarker • Journal • Lung Cancer • Oncology • Pneumonia • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Multicenter phase II study of cisplatin and gemcitabine plus necitumumab in patients with unresectable, advanced lung squamous cell carcinoma who have progressed on or after initial treatment with immune checkpoint inhibitors plus platinum-based chemotherapy: WJOG14120L NESSIE study (ESMO 2024) - "CGN demonstrated moderate efficacy and good tolerability in patients who have progressed on or after front-line ICIs plus PBC, although the primary endpoint was not met."

Checkpoint inhibition • Clinical • Metastases • P2 data • Non Small Cell Lung Cancer • Oncology

QUILT-3.090: NANT Squamous Cell Carcinoma (SCC) Vaccine: Subjects With SCC Who Have Progressed (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: ImmunityBio, Inc. | N=65 ➔ 4 | Unknown status ➔ Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Enrollment change • Trial termination • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

SQUIRE: First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin (clinicaltrials.gov) - P3 | N=1093 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Metastases • Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS

Effects of N361 Glycosylation on Epidermal Growth Factor Receptor Biological Function. (PubMed, bioRxiv) - "EGFR transduces signals from growth factors into cell proliferation and is frequently hyperactivated in tumors. Glycosylation of EGFR at N361 regulates EGFR dimerization, growth factor stimulation of proliferative signaling, and susceptibility to targeted inhibition. Insights into EGFR glycosylation may expand therapeutic opportunities to benefit cancer patients."

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

Enhancing neutrophil cytotoxicity of a panel of clinical EGFR antibodies by Fc engineering to IgA3.0. (PubMed, Mol Cancer Ther) - "Therefore, we reformatted six therapeutic EGFR antibodies (cetuximab, panitumumab, nimotuzumab, necitumumab, zalutumumab, and matuzumab) into the IgA3.0 format, which is an IgA2 isotype that has been adapted for clinical application. IgA3.0 matuzumab exhibited reduced receptor internalization compared to the other antibodies, possibly accounting for its superior in vivo Fc-mediated tumor cell killing efficacy. In conclusion, reformatting EGFR antibodies into an IgA3.0 format increased Fc-mediated killing while retaining Fab-mediated functions and could therefore be a good alternative for the currently available antibody therapies."

Journal • Oncology • EGFR

A case of stage I breast cancer in which CR was achieved with FOLFIRI + Panitumumab for concurrent stage IV rectal cancer (JBCS 2024) - "Regarding breast cancer treatment with EGFR targeted drugs, necitumumab, the same anti-EGFR antibody drug that is currently only applicable to lung squamous cell carcinoma, is used as advanced medical treatment for breast cancer, esophageal cancer, gastric cancer, etc., and research into treatments for TNBC and inflammatory breast cancer is also underway, so there may be new developments in the future. Conclusion We experienced a case of breast cancer that achieved CR after drug therapy for rectal cancer. The possibility that the anti-EGFR antibody drug contributed to the therapeutic effect could not be denied"

Clinical • Metastases • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Rectal Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • ER • HER-2 • PGR

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 | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • 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 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Jun 2025

Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • 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) - "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

SQUIRE: First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin (clinicaltrials.gov) - P3 | N=1093 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2023 ➔ Jun 2024

Metastases • Trial completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KRAS

Association between skin toxicity and efficacy of necitumumab in squamous non-small-cell lung cancer: a pooled analysis of two randomized clinical trials-SQUIRE and JFCM. (PubMed, ESMO Open) - "A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy."

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