TheraCIM (nimotuzumab)

P2, N=20, Enrolling by invitation, The First Affiliated Hospital of Xiamen University

We used the combined chemotherapy of gemcitabine (1,000 mg/m2) + oxaliplatin (135 mg/m2) + nimotuzumab (400 mg). Then, the patients were treated with oral olaparide (600 mg/day) for one year, and survived without tumor progress for more than 1.5 years. These two cases achieved excellent effects of precise chemotherapy, which provided an important reference for the treatment of pancreatic cancer patients with wild KRAS and mutant BRCA.

P=N/A, N=980, Completed, Xiangya Hospital of Central South University; Xiangya Hospital of Central South University

P2, N=37, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | Trial completion date: Oct 2020 --> Oct 2027 | Trial primary completion date: Oct 2018 --> Oct 2025

P3, N=354, Recruiting, Biotech Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

EGFR and PD-L1 are highly expressed in OSCC, the combination of which is important for a precise prognosis of OSCC. EGFR and PD-L1 expression can be sensitively detected using the newly synthesized multispectral fluorescence imaging probes Nimotuzumab-ICG and Atezolizumab-Cy5.5, which can facilitate the sensitive and specific detection of OSCC and improve treatment outcomes.

P3, N=416, Not yet recruiting, Sun Yat-sen University

P2, N=30, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=31, Not yet recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital

P2, N=31, Recruiting, Fujian Cancer Hospital; Fujian Cancer Hospital

In a HNSCC tumor-bearing model, nimotuzumab significantly decreased PD-L1 expression during tumor progression or chemotherapy, and this reduction was accompanied by increased sensitivity of the tumor to docetaxel and atezolizumab. Additionally, nimotuzumab reversed PD-L1 upregulation when combined with Taxol + Cisplatin (TP) induction chemotherapy regimens and improved the CD4+ and CD8+ T cells infiltration in HNSCC patients. These findings provide new insights into the anticancer mechanisms of nimotuzumab in HNSCC.

P2, N=20, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

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.

Our study highlights a more superior combined efficacy of nimotuzumab and gemcitabine than the control regimen, exhibiting improved survival and reduced levels of CA724, CA19-9, and CEA in patients with advanced pancreatic cancer.

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.

P=N/A, N=299, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P2, N=37, Recruiting, Fujian Cancer Hospital

P2, N=55, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=31, Active, not recruiting, Peking Union Medical College Hospital

P2, N=73, Not yet recruiting, Peking University Third Hospital

P2, N=55, Completed, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Recruiting --> Completed | Trial completion date: Aug 2022 --> Jun 2023

P2, N=30, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=53, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2/3, N=146, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=30, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=30, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=30, Completed, Zhejiang Cancer Hospital | Unknown status --> Completed | Trial completion date: Dec 2019 --> Dec 2023

P2, N=50, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

This proposition was validated in our in vitro and in vivo studies where melatonin synergistically augmented cytotoxicity and apoptosis in Nimotuzumab-treated glioma cells. Thus, melatonin shows promise as a beneficial addition to Nimotuzumab treatment in glioma patients.

P3, N=90, Completed, Biotech Pharmaceutical Co., Ltd. | Unknown status --> Completed | N=276 --> 90

P3, N=420, Not yet recruiting, Biotech Pharmaceutical Co., Ltd.

In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG-b-P(GMA-ss-DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.

Anti-CD20 [225Ac]Ac-macropa-rituximab was developed and used as a nonspecific radioimmunoconjugate. Compared with untreated mice, [225Ac]Ac-macropa-nimotuzumab more than doubled (16 vs. 41 d) the median survival of mice bearing SW620 xenografts. [225Ac]Ac-macropa-nimotuzumab is effective against KRAS mutant and BRAFV600E mutant CRC models.

Whole-exome sequencing showed that DYNC1I2, THSD7A, and FAT1 mutations were associated with patient prognosis. Combination therapy involving tislelizumab plus nimotuzumab is a promising, low-toxicity treatment for recurrent or metastatic OSCC in patients with a PS score ≥ 2.

P2, N=48, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Jun 2024

P3, N=710, Active, not recruiting, National Cancer Centre, Singapore | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1/2, N=36, Recruiting, University of Saskatchewan | Trial completion date: Mar 2024 --> Oct 2026 | Trial primary completion date: Sep 2023 --> Sep 2026

P1/2, N=14, Recruiting, University of Saskatchewan | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Jun 2023 --> Sep 2026

P2, N=292, Recruiting, Sun Yat-sen University Cancer Center ; Sun Yat-sen University Cancer Center | Not yet recruiting --> Recruiting

In patients with locally advanced or metastatic K-Ras wild-type PC, nimotuzumab plus gemcitabine significantly improved OS and PFS with a good safety profile.

Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.