TheraCIM (nimotuzumab)

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.

P1/2, N=7, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed

Concurrent nimotuzumab with IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC medically unfit for concomitant chemotherapy. Further clinical trials are needed to confirm these findings.

Nimotuzumab combined with concurrent chemo-radiotherapy improved the ORR, and prolonged PFS and OS in unresectable ESCC patients with a good tolerance.

The neoadjuvant chemoradiotherapy combined with nimotuzumab and camrelizumab was with high surgical conversion rate and acceptable safety in initially inoperable patients with locally advanced esophageal cancer.

In summary, our data indicated that miR-199a/214 cluster play a crucial role in enhancing the inhibitory effect of nimotuzumab on PCa development by downregulating TBL1XR1 and modulating Wnt/β-catenin and EGFR signaling pathways. These findings offer a novel therapeutic approach for the treatment of prostate cancer.

Meanwhile, treatment with theasinensin A and nimotuzumab prevented xenograft growth, whereas the single agents had limited effect. Thus, the combination therapy of theasinensin A with nimotuzumab is a powerful candidate for treatment of wild-type EGFR cancers.

These results identified low-dose obinituzumab as a promising treatment option in children with steroid-dependent or frequently relapsing nephrotic syndrome, including those resistant to rituximab. The tolerance profile of obinutuzumab appears similar to that of rituximab, but hemogram and immunoglobulin levels should be monitored.

Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted.

P=N/A, N=46, Recruiting, Tianjin Medical University Second Hospital

For A549 cells, the IC value of the AuNP-NmAb conjugate was 163.6 µg/mL, while the IC value of free NmAb was 1,082.0 µg/mL. Therefore, this study highlights the unique therapeutic potential of AuNP-NmAb in EGFR+ cancers and shows the potential to develop other mAb nanoparticle complexes for a superior therapeutic efficacy.

In conclusion, our work uncovers that EGFR-mAb Nimotuzumab combined with Wee1 inhibitor AZD1775 elicited potentiated anticancer activity against ESCC cell line and PDXs partially through PI3K/Akt and MAPK pathways blockade. These pre-clinical data raise the promising that ESCC patients may benefit from dual target EGFR and Wee1.

P3, N=354, Not yet recruiting, Biotech Pharmaceutical Co., Ltd.

Methods All patients with locally advanced cervical squamous cell carcinoma were randomized (1:1) to receive nimotuzumab (400mg, iv, weekly, for 6 weeks) combined with CCRT (cisplatin: 40 mg/m2, weekly, for 6 weeks; IMRT/VMAT: 45-50.4 Gy/25-28f; high-dose rate brachytherapy: 30-40 Gy, in 8 weeks) or CCRT alone. The incidence of grade 3 or higher adverse reactions had no significant difference between the two groups (P>0.05). Conclusions Nimotuzumab combined with concurrent chemo-radiotherapy showed longer survival trend and significantly improved the ORR in patients of locally advanced cervical squamous cell carcinoma with a good tolerance.

We found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC.

In a phase III study, intensity-modulated radiotherapy alone showed comparable survival to combined radiochemotherapy with cisplatin in selected low-risk patients. In high-risk patients, addition of the EGFR antibody nimotuzumab to definitive radiochemotherapy showed an increased 5‑year survival rate compared to placebo (phase III study). Although an immediate change in clinical practice in Europe based on these studies is questionable, the concept of risk-adapted therapy taking into account biological characteristics (Epstein-Barr virus [EBV] DNA level) is future orientated. Similar to previous years, the contributions on recurrent/metastatic salivary gland and thyroid cancer emphasized the importance of targeted therapies based on vulnerable molecular target lesions.

Nab-paclitaxel-based regimen could be a safe and effective option as second- or later-line treatment in patients with advanced ESCC, regardless of their previous exposure to PD-1 inhibitors.

P2, N=55, Recruiting, Health Science Center of Xi'an Jiaotong University | Active, not recruiting --> Recruiting

Survival benefits were increased in those patients who received 8 or more doses of nimotuzumab. This trial is registered with RPCEC00000245 in the Cuban Registry of Clinical Trials, part of the World Health Organization's International Clinical Trials Registry Platform (ICTRP).

The first line treatments included acalabrutinib based 42(12.8%), Ibrutinib based 43(13.1%), Zanubrutinib 23(7%) venetoclax/obinituzumab 23(7%), Ibrutinib/venetoclax 9(2.7%), Idelalisib/Rituximab 6 (1.8%), fludarabine based 82(25%), chlorambucil based 60(18.3%), bendamustine based 22(6.7%), alemtuzumab based 15(4.6%) and others 3(0.9%). In this real word study, it has been shown that there is no OS advantage from initiating patients on targeted therapy as first line compared to chemoimmunotherapy followed by targeted therapy on relapse. This concept should be validated from multi-centric data and possibly tested in prospective trials. B-CLL

Although some Mabs have shown promising outcomes in SCC therapy, their application as a part of cancer treatment depends on further investigations regarding cost-effectiveness and predictors of response. FDA has approved several Mabs in SCC therapies, and Mabs may have a crucial role in this era in the near future, especially in treating head and neck and esophageal SCC and metastatic lung cancer.

P2, N=57, Not yet recruiting, Peking Union Medical College Hospital

CCRT of CC may have a short-term negative impact on the peripheral T-cell immune micro-environment, and the combination of nimotuzumab, cisplatin-based chemotherapy, and radiotherapy enhances the frequency of Tregs in peripheral blood. Our findings illustrated that nimotuzumab combined with CCRT can improve the imbalance of T lymphocyte subsets in peripheral blood of patients with middle-advanced CC. A better understanding of the mechanisms of these therapies will optimise the selection of patients most likely to benefit from treatment, serving as a reference for further research on the relationship between EGFR-specific T cells and clinical benefit in patients treated with nimotuzumab in combination with CCRT.

P3, N=459, Recruiting, Fudan University

For locally advanced NPC patients treated with concurrent chemoradiotherapy, the addition of NTZ can significantly improve their survival outcome. However, it is necessary to guard against the associated increase in hematological toxicity and acute oral mucositis.

P3, N=384, Recruiting, Sun Yat-sen University | Trial primary completion date: Feb 2022 --> Feb 2024

Nimo combined with CRT can protect the immune function of patients, improve the effective rate, and prolong the survival rate of patients with IACC.

Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability.