HuMax-EGFR (zalutumumab) / Genmab - LARVOL DELTA

Evaluating Antigen-Antibody Interactions: A Comparative Study of Higher-Order Structural MS Methods. (PubMed, J Am Soc Mass Spectrom) - "In this study, we probed interaction sites of epidermal growth factor receptor (EGFR) with cetuximab and zalutumumab using HDX, covalent labeling, and cross-linking techniques. DEPC labeling has more residue coverage compared to sulfo-NHS acetate but faces unique challenges like faster hydrolysis and more complex modifications. We further extended the use of covalent labeling experiments in a cellular environment with the same model system and with results consistent with purified proteins, making covalent labeling a suitable method to screen epitopes for complex targets and receptors directly from cells."

Clinical • Journal • EGFR

Verification study of Genomic Adjusted Radiation Dose (GARD) in HNSCC patients from the DAHANCA19 trial (ESTRO 2026) - "Cisplatin 40 mg/m2 was given concomitantly to majority of patients (n=144)...DAHANCA 19: A Randomized Phase III Study of Primary Curative (Chemo)-Radiotherapy and the EGFRInhibitor Zalutumumab for Squamous Cell Carcinoma of the Head and Neck... The GARD stratification has a limited prognostic value for locoregional failure in Danish HNSCC patients. References: 1.Scott JG, Berglund A, Schell MJ, et al. A genomebased model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study."

Clinical • Head and Neck Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IBI3001: A potentially first-in-class site-specifically conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors (AACR 2024) - "We previously demonstrated in IBI334 (B7-H3/EGFR bsAb) study that (1) B7-H3 and EGFR are co-expressed in multiple solid tumors; (2) B7-H3-aided EGFR signaling inhibition was significantly more potent than Zalutumumab (EGFR mAb) and Amivantamab (c-met/EGFR bsAb); and (3) IBI334 has favorable safety profile in cynomolgus monkey at 120 mg/kg/week. IBI3001 has a favorable PK profile in BALB/c mice with the half-life at 282 hours, and is well-tolerated in cynomolgus monkeys up to 90 mg/kg/week. In conclusion, IBI3001 is a novel bispecific ADC that demonstrated strong anti-tumor efficacy cross multiple solid tumors, and has excellent PK and safety profile."

ADC • Bispecific • Late-breaking abstract • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD276 • EGFR • MET

IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors (AACR 2024) - "Antibodies that inhibit EGFR signaling, such as Cetuximab, show clinical efficacy but are associated with on-target toxicities that potentially limit the drug efficacy...With the aid of B7-H3, IBI334 showed enhanced EGFR signal inhibition than Zalutumumab (EGFR mAb) and Amivantamab (c-met/EGFR bsAb)...In conclusion, IBI334 is a potent B7-H3/EGFR bispecific antibody with broad application in many EGFR-driven solid tumors. The large therapeutic window enables safe and effective cancer treatment at high exposure levels."

ADC • Bispecific • Late-breaking abstract • Preclinical • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • CD276 • KRAS • MET

Radiotherapy quality assurance of patients with squamous cell carcinoma of the head and neck included in the DAHANCA 19 randomised phase III trial. (PubMed, Radiother Oncol) - "The treatment plans in DAHANCA 19 adhered well to national guidelines. Most major deviations were observed in the experimental arm but did not affect the local treatment control. No indication that compromised RT-QA affected the conclusions of DAHANCA 19 was found."

Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DAHANCA19: A randomized phase III study of primary curative (chemo)-radiotherapy and the EGFR-inhibitor zalutumumab for squamous cell carcinoma of the head and neck. (PubMed, Radiother Oncol) - "Addition of concomitant zalutumumab to primary (chemo-)radiotherapy and concomitant nimorazole for HNSCC did not increase locoregional control nor disease-specific or overall survival."

Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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

Anti‑epidermal growth factor receptor monoclonal antibody therapy in locally advanced head and neck cancer: A systematic review of phase III clinical trials. (PubMed, Med Int (Lond)) - "Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC."

Journal • Metastases • P3 data • Review • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

MACH-EGFR: Individual patient data (IPD) meta-analysis of anti-EGFR monoclonal antibodies (Ab) in patients (pts) with locally advanced (LA) squamous cell carcinomas of head and neck (SCCHN) (ESMO 2023) - "Table: 857O Comparison 1 Comparison 2 Trials Nb trials (Nb pts) 9 (3097) 10 (3036) Anti-EGFR Ab cetuximab 5 (1686) 8 (2565) nimotuzumab 2 (642) 0 panitumumab 1 (150) 2 (471) zalutumumab 1 (619) 0 Patients/tumors Nb pts (%) Male 2617 (85%) 2602 (86%) < 60 years 1854 (60%) 1700 (56%) ≥ 60 years 1243 (40%) 1336 (44%) ECOG PS 0 1861 (60%) 2181 (72%) 1 1185 (38%) 847 (28%) 2 33 (1%) 4 (<1%) Location Larynx 691 (22%) 219 (7%) Hypopharynx 437 (14%) 295 (10%) Oral cavity 89 (3%) 185 (6%) Oropharynx 1875 (61%) 2329 (77%) p16 positive/negative/UK 631/413/831 1784/100/445 Stage (AJCC 7) I-II 67 (2%) 15 (<1%) III 552 (18%) 383 (13%) IV 2476 (80%) 2634 (87%) Median follow-up (years) 4.0 3.9 Number of deaths (% of pts) 1209 (39%) 798 (26%) Conclusions There was no survival benefit with the addition of Ab to LRT for either comparison. Importantly, replacing CT with anti-EGFR Ab, as systemic treatment added to LRT, results in inferior survival."

Metastases • Retrospective data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Comparison of Second-Line Treatments for Patients with Platinum-Resistant Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Systematic Review and Bayesian Network Meta-Analysis. (PubMed, Cancers (Basel)) - "These studies compared 20 different treatments, including the standard of care (SOC: docetaxel, methotrexate, or cetuximab), PD-1 inhibitors (nivolumab or pembrolizumab), durvalumab, tremelimumab, durvalumab + tremelimumab, palbociclib + SOC, tivantinib + SOC, sorafenib + SOC, EMD1201081 + SOC, vandetanib + SOC, PX-866 + SOC, 5-fluorouracil + SOC, cixutumumab + SOC, gefitinib + SOC, cabazitaxel, nolatrexed, duligotuzumab, zalutumumab, gefitinib, and afatinib. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS."

Journal • Retrospective data • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Epidermal Growth Factor Receptor as Target for Perioperative Elimination of Circulating Colorectal Cancer Cells. (PubMed, J Oncol) - "Three different anti-EGFR mAbs (cetuximab, zalutumumab, and panitumumab) were equally efficient in the opsonization of tumor cell lines. These data support the use of a low dose of anti-EGFR mAbs prior to resection of the tumor to eliminate CTCs without interfering with the healing of the anastomosis. Ultimately, this may reduce the risk of metastasis development, consequently improving long-term patient outcome significantly."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CTCs • EGFR

Management of recurrent and metastatic oral cavity cancer: Raising the bar a step higher. (PubMed, Oral Oncol) - "The backbone of cytotoxic chemotherapy remains cisplatin with 5-fluorouracil or a taxane. In contrast to cisplatin, the tumoricidal activity of carboplatin monotherapy is debatable...Interestingly, three large randomized trials (EXTREME, SPECTRUM, and ZALUTE) evaluating different anti-EGFR monoclonal antibodies (cetuximab, panitumumab, and zalutumumab, respectively) demonstrated preferential anti-tumour efficacy in patients with primary cancer in the oral cavity. Modern immunotherapy with immunomodulating antibodies, dubbed immune checkpoint inhibitors, such as anti-programmed cell death protein-1 (anti-PD-1) inhibitors nivolumab and pembrolizumab, showed unprecedented activity in one first-line (KEYNOTE-048) and several second-line trials (CheckMate-141, KEYNOTE-012, KEYNOTE-055, and KEYNOTE-040)...In oligometastatic disease, emerging data indicate long-term benefit with locally ablative techniques including metastasectomy and stereotactic radiotherapy of pulmonary but..."

Journal • Head and Neck Cancer • Immune Modulation • Inflammation • Oncology • Oral Cancer • Palliative care • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis. (PubMed, Immunotherapy) - " Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments."

Checkpoint inhibition • Journal • Retrospective data • Head and Neck Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Zalutumumab in non-small cell lung cancer (NSCLC) patients refractory to tyrosine kinase inhibitors (clinicaltrials.gov) - P2, N=0; Withdrawn prior to enrollment (Trial never initiated)

Trial withdrawn • Oncology

An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck (Cancer Chemother Pharmacol) - P2, N=90; Sponsor: Genmab; NCT00542308; “Median OS was 5.3 months (95 % CI [4.1, 7.1]), and median PFS was 2.1 months (95 % CI [2.0, 2.6]). Subgroup analysis by ECOG PS revealed median OS of 6.3 months for PS = 0-1 and 2.5 months for PS = 2. Objective response rate was 5.7 %, and disease control rate was 39.8 %."

P2 data • Head and Neck Cancer • Oncology

[Late breaking abstract] DAHANCA 19: First results of a randomized phase III study of the importance of the EGFR-inhibitor zalutumumab for the outcome of primary curative radiotherapy for squamous cell carcinoma of the head and neck (ESMO-ECCO-ESTRO 2013) - Presentation time: 30 September 2013, 13:50; Abstract# 12; P3, N=619; NCT00496652; “The 3-year LRC rate was 78% in the zalutumumab-arm vs. 79% in the control-arm, HR: 0.8 [95% CI: 0.6-1.2]. This outcome was reflected in DSS: HR 1.0 [0.7-1.7] and OS: HR 0.9 [0.6-1.3]. Effect of zalutumumab was not influenced by p-16 positivity (HR 1.0 [0.6-1.8]) nor p-16 negativity (HR 0.8 [0.5-1.4]).”

P3 data • Head and Neck Cancer • Oncology