ATG-031 for Cancer
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Antengene Biologics Limited
Must not be taking: Corticosteroids, Chemotherapy, Immunotherapy, others
Disqualifiers: CNS malignancies, Autoimmune diseases, HIV, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?ATG-031 study (alias: PERFORM) is a multicenter, open-label, Phase 1 study of ATG-031 in patients with advanced solid tumors or B-NHL. The study design includes a Dose Escalation Phase and a Dose Expansion Phase, and will enroll patients with advanced solid tumors (i.e., preferred tumor types) or relapsed/refractory (R/R) B-NHLs. The study's primary objective is to evaluate the safety and tolerability of ATG-031 and determine the RP2D（Refered Phase II dose） of ATG-031.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any other investigational product or prior systemic anticancer therapy within 21 days before the first dose of the study treatment.
What data supports the effectiveness of the drug ATG-031 for cancer?
The research shows that drugs similar to ATG-031, like PD-L1 inhibitors, have been effective in improving survival when combined with chemotherapy in certain cancers, such as small cell lung cancer and triple-negative breast cancer. This suggests that ATG-031 might also be effective in treating cancer by potentially working in a similar way.
12345What makes the drug ATG-031 unique for cancer treatment?
ATG-031 is unique because it targets CHI3L1, a protein involved in cancer cell growth and spread, which is not commonly targeted by other cancer treatments. This approach may offer a new way to slow down or stop cancer progression by interfering with the tumor's ability to grow and invade other tissues.
678910Eligibility Criteria
This trial is for adults with advanced solid tumors or B-cell Non-Hodgkin Lymphomas that have not responded to standard treatments. Participants must have good kidney function, adequate blood counts without recent transfusions, and stable enzyme levels indicating proper liver function.Inclusion Criteria
My blood counts meet the required levels without needing transfusions or growth factors recently.
My liver functions are within the required limits.
My cancer has not responded to standard treatments.
+1 more
Exclusion Criteria
I have not had any other cancer types in the last 5 years.
Active hepatitis B and/or hepatitis C (HBV-DNA or HCV-RNA detectable by local laboratory, respectively)
I have a significant heart condition.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive escalating doses of ATG-031 to evaluate safety and determine the RP2D
Approximately 1 year
Multiple visits as per dose escalation protocol
Dose Expansion
Participants receive the determined RP2D of ATG-031 to further evaluate safety and efficacy
Duration depends on cohort expansion
Follow-up
Participants are monitored for safety and effectiveness after treatment
90 days
Participant Groups
The PERFORM study is testing a new medication called ATG-031 in two phases: first to find the safest dose (Dose Escalation Phase) and then to see how well it works at that dose (Dose Expansion Phase).
8Treatment groups
Active Control
Group I: ATG-031 dose level 1Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 0.03 mg/kg
Group II: ATG-031 dose level 5Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 2.0 mg/kg
Group III: ATG-031 dose level 6Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 4.0 mg/kg
Group IV: ATG-031 dose level 4Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 1.0 mg/kg
Group V: ATG-031 dose level 2Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 0.1 mg/kg
Group VI: ATG-031 dose level 7Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 6.0 mg/kg
Group VII: ATG-031 dose level 8Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 9.0 mg/kg
Group VIII: ATG-031 dose level 3Active Control1 Intervention
Patients with advanced solid tumors or B-cell non-Hodgkin lymphomas will be enrolled in the Dose-Escalation Phase.
Dose level is 0.3 mg/kg
ATG-031 is already approved in United States for the following indications:
🇺🇸 Approved in United States as ATG-031 for:
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale UniversityNew Haven, CT
Regents of the University of ColoradoAurora, CO
University of Texas M.D. Anderson Cancer CenterHouston, TX
University of California San Francisco (UCSF)San Francisco, CA
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Who Is Running the Clinical Trial?
Antengene Biologics LimitedLead Sponsor
References
Study: Atezolizumab Improves Survival in SCLC. [2019]Combining the PD-L1 inhibitor atezolizumab with platinum-based chemotherapy improves overall survival among patients with extensive-stage small cell lung cancer relative to chemotherapy alone. These findings could lead to a new first-line treatment option for patients with the disease.
PD-L1 Inhibitor Improves Survival in TNBC. [2019]Combining the PD-L1 inhibitor atezolizumab with standard chemotherapy improves overall survival among patients with metastatic triple-negative breast cancer relative to chemotherapy alone. These findings could lead to a new treatment option for patients with this disease.
pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. [2018]Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.
Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. [2020]PD-1 axis blockade, in combination with chemotherapy, improves outcomes in advanced triple-negative breast cancer that is PD-L1 positive. The phase 3 KEYNOTE-522 trial now shows that the addition of pembrolizumab to chemotherapy improves pathological complete response rates regardless of PD-L1 status and appears to improve survival.
SCGN and STAT3 expressions are associated with the prognosis of ccRCC. [2023]Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and accounts for about 70% of RCC. Its prognosis is worse than that of most histological types of RCC. In order to find potential biomarkers that may influence the prognosis and survival in ccRCC patients, we explored the expressions of STAT3, PDL1 and SCGN (secretagogin) in ccRCC based on the data of TCGA (n = 529), EMATAB-1980 (n = 99) and our own cohort (n = 99). Our study demonstrated that ccRCC patients with low STAT3 expression and high SCGN expression might have a better prognosis. No significant difference in the positive rate of SCGN expression was found when comparing the primary lesion with the matched metastatic liver lesions. The percentage of high SCGN expression in the primary lesion of metastatic ccRCC patients was significantly lower than that of patients with only the renal lesion. In view of the conclusion that STAT3 high expression cases are resistant to sunitinib, STAT3 immunohistochemistry results are essential for designing non-operative treatments. SCGN has the potential to become an indicator for subtype classification of ccRCC.
Chitinase-3 like-protein-1 function and its role in diseases. [2021]Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+ T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.
Pan-Cancer Analysis of Pentraxin 3: A Potential Biomarker of COVID-19. [2022]Pentraxin 3 (PTX3), a potential biomarker of the severity and mortality of COVID-19 patients, is aberrantly expressed in human tumors. However, a comprehensive pan-cancer analysis of PTX3 remains to be elucidated. PTX3 data profiles and clinical information in TCGA cancers were obtained from different public databases to clarify the expression levels, genetic alterations, prognostic significance, underlying mechanisms, and the predicted role in immunotherapy of PTX3 across TCGA cancers. Our analyses showed that PTX3 was aberrantly expressed in most tumors and was significantly related to prognosis and tumor stage. Interaction network and enrichment analyses revealed that PTX3 participated in tumor immuno-related progression. In addition, PTX3 levels were critically associated with immune cell components and immune scores, and PTX3 strongly coexpressed with immune-related genes in TCGA cancers. Meanwhile, PTX3 expression was associated with immune checkpoint genes, and immunotherapy potential biomarkers in multiple cancers, predicting special immunotherapy responses in different tumor types. In kidney renal clear cell carcinoma (KIRC), PTX3 emerged as an independent prognostic factor through multivariable Cox regression analyses. Blocking PTX3 with siRNA could suppress the growth of KIRC cells and invasion. Conclusively, our study shows a comprehensive bioinformatic analysis of PTX3, which might serve as a pan-cancer prognostic biomarker.
C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma. [2021]Objective: Targeting cancer-specific messenger RNAs (mRNAs) may offer novel insights into therapeutic strategies in osteosarcoma. This study aimed to discover possible osteosarcoma-specific mRNA and probe its biological functions. Methods: Based on mRNA-seq data from the TARGET database, stromal and immune scores were estimated for each osteosarcoma sample via the ESTIMATE algorithm. Stromal and immune mRNAs were obtained via integration of differentially expressed mRNAs between high and low stromal / immune score groups. Among hub and prognostic mRNAs, C3AR1 mRNA was focused and its prognostic value was assessed. The associations between C3AR1 mRNA and immune cells were analyzed via the CIBERSORT algorithm. Its expression was verified in osteosarcoma tissues and cells by RT-qPCR and western blot. The functions of C3AR1 were investigated by a series of experiments. Results: Low stromal and immune scores were both indicative of unfavorable outcomes for osteosarcoma patients. Eighty-eight up-regulated and seven down-regulated stromal and immune mRNAs were identified. Among 30 hub mRNAs, low expression of C3AR1 mRNA indicated worse outcomes than its high expression. There was a lower mRNA expression of C3AR1 in metastatic than non-metastatic osteosarcoma. C3AR1 mRNA was closely correlated to various immune cells such as macrophages. C3AR1 was verified to be down-regulated in osteosarcoma tissues and cells. Its overexpression suppressed proliferation, migration and invasion and induced apoptosis in osteosarcoma cells. Conclusion: C3AR1 mRNA could be a promising therapeutic target for osteosarcoma, linked with prognosis and tumor microenvironment.
High expression of CX3CL1 by tumor cells correlates with a good prognosis and increased tumor-infiltrating CD8+ T cells, natural killer cells, and dendritic cells in breast carcinoma. [2022]CX3CL1 is the only CX3C chemokine that can chemoattract T cells, natural killer (NK) cells, and dendritic cells (DCs). The role of CX3CL1 in breast carcinoma remains unknown.
A systematic pan-cancer analysis reveals the clinical prognosis and immunotherapy value of C-X3-C motif ligand 1 (CX3CL1). [2023]It is now widely known that C-X3-C motif ligand 1 (CX3CL1) plays an essential part in the process of regulating pro-inflammatory cells migration across a wide range of inflammatory disorders, including a number of malignancies. However, there has been no comprehensive study on the correlation between CX3CL1 and cancers on the basis of clinical features. In order to investigate the potential function of CX3CL1 in the clinical prognosis and immunotherapy, I evaluated the expression of CX3CL1 in numerous cancer types, methylation levels and genetic alterations. I found CX3CL1 was differentially expressed in numerous cancer types, which indicated CX3CL1 may plays a potential role in tumor progression. Furthermore, CX3CL1 was variably expressed in methylation levels and gene alterations in most cancers according to The Cancer Genome Atlas (TCGA). CX3CL1 was robustly associated with clinical characteristics and pathological stages, suggesting that it was related to the degree of tumor malignancy and the physical function of patients. As determined by the Kaplan-Meier method of estimating survival, high CX3CL1 expression was associated with either favorable or unfavorable outcomes depending on the different types of cancer. It suggests the correlation between CX3CL1 and tumor prognosis. Significant positive correlations of CX3CL1 expression with CD4+ T cells, M1 macrophage cells and activated mast cells have been established in the majority of TCGA malignancies. Which indicates CX3CL1 plays an important role in tumor immune microenvironment. Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the chemokine signaling pathway may shed light on the pathway for CX3CL1 to exert function. In a conclusion, our study comprehensively summarizes the potential role of CX3CL1 in clinical prognosis and immunotherapy, suggesting that CX3CL1 may represent a promising pharmacological treatment target of tumors.