ATG-031 for Cancer

Recruiting at 3 trial locations

Overseen By Ran Wei

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Antengene Biologics Limited

Must not be taking: Corticosteroids, Chemotherapy, Immunotherapy, others

Disqualifiers: CNS malignancies, Autoimmune diseases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

What 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. ^{6 7 8 9 10}

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.

Eligibility 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.

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.

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

Treatment Details

Interventions

• ATG-031

Trial Overview 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).

Participant Groups

Group I: ATG-031 dose level 1 Active Control 1 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 5 Active Control 1 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 6 Active Control 1 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 4 Active Control 1 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 2 Active Control 1 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 7 Active Control 1 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 8 Active Control 1 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 3 Active Control 1 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:

Who Is Running the Clinical Trial?

Antengene Biologics Limited

Lead Sponsor

Trials

3

Recruited

240+

Findings from Research

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

The combination of the PD-L1 inhibitor atezolizumab with standard chemotherapy significantly improves overall survival in patients with metastatic triple-negative breast cancer compared to chemotherapy alone.

This research suggests that adding atezolizumab could provide a new treatment option for patients suffering from this aggressive form of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitor Improves Survival in TNBC. [2019]

In a study of 154 patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (SCC), high levels of activated STAT3 (pSTAT3) were linked to worse survival outcomes in SCC, while higher pSTAT3 levels in OAC were associated with better survival, indicating a complex role of STAT3 in different cancer types.

Treatment with the STAT3 inhibitor STATTIC in cancer cell lines led to reduced survival, proliferation, and migration, along with increased apoptosis, suggesting that targeting STAT3 could be a promising therapeutic strategy for both OAC and SCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. O' Sullivan, KE., Michielsen, AJ., O' Regan, E., et al.[2018]

The phase 3 KEYNOTE-522 trial demonstrated that adding pembrolizumab, a PD-1 axis blocker, to chemotherapy significantly improves pathological complete response rates in patients with advanced triple-negative breast cancer, regardless of their PD-L1 status.

This combination therapy not only enhances treatment effectiveness but also appears to improve overall survival rates for patients with this aggressive form of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. Savas, P., Loi, S.[2020]

In a study involving 727 clear cell renal cell carcinoma (ccRCC) patients, low expression of STAT3 and high expression of SCGN were associated with better prognosis, suggesting these markers could help predict patient outcomes.

The research indicates that high STAT3 expression may lead to resistance against sunitinib treatment, highlighting the importance of STAT3 immunohistochemistry in guiding non-operative treatment strategies for ccRCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SCGN and STAT3 expressions are associated with the prognosis of ccRCC. Lai, C., Gong, J., Tang, J., et al.[2023]

CHI3L1 is a protein involved in various biological processes such as inflammation, tissue repair, and cancer progression, and is linked to several diseases including asthma, arthritis, and various cancers.

Targeted therapies based on CHI3L1 are being explored for treating tumors like glioma and colon cancer, highlighting its potential as a therapeutic target in oncology and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chitinase-3 like-protein-1 function and its role in diseases. Zhao, T., Su, Z., Li, Y., et al.[2021]

Pentraxin 3 (PTX3) is found to be abnormally expressed in most types of cancer and is significantly linked to patient prognosis and tumor stage, suggesting its potential as a pan-cancer prognostic biomarker.

In kidney renal clear cell carcinoma (KIRC), PTX3 not only serves as an independent prognostic factor but also blocking its expression can inhibit cancer cell growth and invasion, highlighting its role in tumor progression and potential therapeutic target.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-Cancer Analysis of Pentraxin 3: A Potential Biomarker of COVID-19. Zhou, Z., Zhou, X., Yang, Y., et al.[2022]

C3AR1 mRNA is identified as a potential therapeutic target in osteosarcoma, with low expression levels correlating with worse patient outcomes and a higher likelihood of metastasis.

Overexpressing C3AR1 in osteosarcoma cells led to reduced cell proliferation, migration, and invasion, while promoting apoptosis, suggesting its role in regulating tumor behavior and the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma. Zou, T., Liu, W., Wang, Z., et al.[2021]

High expression of CX3CL1 in breast carcinoma is associated with increased levels of immune cells (CD8+ T cells, NK cells, and dendritic cells) and correlates with significantly better disease-free and overall survival rates in patients.

CX3CL1 has been identified as an independent prognostic factor for breast cancer outcomes, suggesting it could serve as a new biomarker and a potential target for developing more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Park, MH., Lee, JS., Yoon, JH.[2022]

CX3CL1 is differentially expressed across various cancer types and is associated with clinical characteristics and tumor stages, indicating its potential role in tumor progression and malignancy.

High levels of CX3CL1 expression correlate with varying patient outcomes depending on the cancer type, and it is linked to immune cell presence in the tumor microenvironment, suggesting it could be a target for immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic pan-cancer analysis reveals the clinical prognosis and immunotherapy value of C-X3-C motif ligand 1 (CX3CL1). Sun, Y.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

PD-L1 Inhibitor Improves Survival in TNBC. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

SCGN and STAT3 expressions are associated with the prognosis of ccRCC. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Chitinase-3 like-protein-1 function and its role in diseases. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pan-Cancer Analysis of Pentraxin 3: A Potential Biomarker of COVID-19. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A systematic pan-cancer analysis reveals the clinical prognosis and immunotherapy value of C-X3-C motif ligand 1 (CX3CL1). [2023]