P1/2, N=360, Recruiting, Merus N.V. | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2024

SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy.

SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Further, these hit compounds were observed to interact with critical residues of the EGFR, suggesting their potential as inhibitors of the receptor. In addition, these hits possess good drug-like properties and merit further exploration for their potential application in cancer management.

In vitro experiments, Orlistat combined with BPI-7711 had reduced IC50 (508.08nM) in comparison with BPI-7711 alone (1328nM)...Meanwhile, fatty acids downregulated FASN and upregulated CPT1A expression, which may reduce the de nove synthesis of fatty acids and influence fatty acid oxidation. Conclusions This study revealed the metabolic landscape of advanced T790M-mutant NSCLC patients, providing the potential guide of personalized third-generation EGFR-TKI treatment and therapeutic target for overcoming resistance.

Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

P1/2, N=81, Completed, Sunshine Lake Pharma Co., Ltd. | Recruiting --> Completed | N=45 --> 81 | Trial completion date: Apr 2023 --> Dec 2022

1 esophageal cancer pt died due to unrelated G5 GI bleeding. Petosemtamab demonstrated promising clinical efficacy among patients with pretreated GEA having EGFR gene amplification and/or overexpression, with a manageable safety profile.

Pts received a median of 2 (range 1-4) lines of prior systemic therapy, including anti-PD-1/PD-L1 in 96% of pts and platinum-based chemotherapy in 92% of pts; 2 pts received prior cetuximab. Petosemtamab demonstrates promising clinical efficacy with a manageable safety profile in pretreated HNSCC pts. Further clinical development in HNSCC is planned with petosemtamab monotherapy and in combination with SOC.

QU524 (CID:46916170), QU571 (CID:44968219) and QU297 (CID:70702306) as the potential anti-EGFR compounds possessing higher binding energy of -8.64 kcal/mol, -8.24 kcal/mol -8.10 kcal/mol, respectively compared to control drug, erlotinib with binding energy of -7.72 kcal/mol. The above selected leads also cleared ADME, toxicity, metabolic reactivity and cardiotoxicity profile filters. Based on the good binding affinity, pharmacokinetic profiling and stability of the bound complexes we propose the selected leads as prominent EGFR inhibitors to halt the phenomenon of tumor angiogenesis.

P2, N=40, Recruiting, National Cancer Center, Korea

P1/2, N=360, Recruiting, Merus N.V. | Unknown status --> Recruiting | Phase classification: P1 --> P1/2 | N=120 --> 360 | Trial completion date: Jan 2021 --> Jun 2024 | Trial primary completion date: Jan 2021 --> Jun 2023

Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting.

The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. MTT assay, gene expression analysis (BAX, BCL-2, and β-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549.

P1, N=40, Completed, RTOG Foundation, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Feb 2022

SCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC.

No abstract available

P1, N=120, Recruiting, Sinocelltech Ltd.

Rezivertinib demonstrated promising efficacy and favorable safety profile for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation.

Fentanyl activates ovarian cancer via simulating EGFR signaling pathways in an opioid µ receptor-dependent manner. The activation of EGFR signaling by fentanyl may provide a new guide in clinical use of fentanyl in ovarian cancer patients.

P3, N=416, Recruiting, Sunshine Lake Pharma Co., Ltd. | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Aug 2022 --> Aug 2023

P2, N=83, Recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Recruiting

The top three TRAEs were white blood cell count decreased (44.2%), platelet count decreased (39.5%), neutrophil count decreased (30.2%). Conclusions Rezivertinib showed promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation at first-line setting.

GE11-modified graphene quantum dots (GQDs@GE11) were used as drug carriers for clinical chemotherapeutics cisplatin (CDDP) and doxorubicin (DOX). In vivo experiments have confirmed that GQDs@GE11/CDDP/DOX nanoprobe can be enriched to tumor site through specific targeting effect, and significantly inhibit tumor cell proliferation. This new type of targeted therapy fluorescent probe provides new ideas for the study of drug release process and the treatment of nasopharyngeal carcinoma.

P1/2, N=45, Recruiting, Sunshine Lake Pharma Co., Ltd. | Active, not recruiting --> Recruiting | Trial completion date: Jun 2021 --> Apr 2023 | Trial primary completion date: Apr 2021 --> Dec 2022

Our drug discovery strategy resulted in the generation of MCLA-158, a bAb that specifically triggers epidermal growth factor receptor degradation in leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cancer stem cells but shows minimal toxicity toward healthy LGR5+ colon stem cells. MCLA-158 exhibits therapeutic properties such as growth inhibition of KRAS-mutant colorectal cancers, blockade of metastasis initiation and suppression of tumor outgrowth in preclinical models for several epithelial cancer types.

Rezivertinib demonstrated promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation.

CPGJ602 plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) may have efficacy in KRAS/NRAS/BRAF wild-type metastatic colorectal cancer. CPGJ602 plus mFOLFOX6 could be an option for KRAS/NRAS/BRAF wild-type metastatic colorectal cancer.

Rezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.

P2, N=83, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Initiation date: Nov 2021 --> Mar 2022 | Trial primary completion date: Mar 2023 --> Oct 2023

SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.

Antagonizing EGFR function with shRNAs, small molecule inhibitors (afatinib, neratinib), or an anti-EGFR antibody (cetuximab) inhibited proliferation of DSRCT cells. Finally, treatment of mice bearing DSRCT xenografts with a combination of cetuximab and afatinib significantly reduced tumor growth. These data provide a rationale for evaluating EGFR antagonists in patients with DSRCT.

P2, N=83, Not yet recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Larotinib demonstrated promising antitumor activity and manageable safety profiles in patients with pre-treated advanced ESCC with EGFR overexpression or amplification, especially at the dose of 350 mg, which showed better efficacy and acceptable safety. A phase 3 study is underway on 350 mg larotinib in ESCC patients with EGFR overexpression.

P2, N=75, Recruiting, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting | Trial completion date: Dec 2021 --> Mar 2022 | Trial primary completion date: Aug 2021 --> Dec 2021

Drug interactions do not occur when panitumumab is combined with chemotherapy drugs including irinotecan, paclitaxel, and carboplatin. The incidence of anti-panitumumab antibodies is low; when anti-panitumumab antibodies are produced, they do not affect the efficacy, safety, or pharmacokinetics of panitumumab. In summary, the pharmacokinetic and pharmacodynamic profile of panitumumab is well suited for standard dosing, and the approved body weight-based dosing regimen maintains efficacy and safety in the treatment of wild-type RAS metastatic colorectal cancer across a broad range of patients.

Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.

This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

The radiomics model based on MRI might have the potential to predict EGFR mutation in patients with lung adenocarcinoma. The multi-sequence model had better performance than other models.

The EGFR mutation status alone was not an independent predictor of objective radiographic response to palliative thoracic radiotherapy. Acquired resistance to TKI therapy may be associated with disease cross-resistance to palliative radiotherapy.