ATG-101 for Advanced Cancers

(PROBE Trial)

Recruiting in Palo Alto (17 mi)

+9 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: 4-1BB agonists

Disqualifiers: CNS tumors, Active infection, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called ATG-101 on patients with advanced cancers to see if it can help treat their condition.

Will I have to stop taking my current medications?

The trial requires that you have not had any anti-tumor systemic therapy within 21 days before starting the study treatment. This means you may need to stop certain cancer treatments before joining the trial.

What data supports the effectiveness of the drug ATG-101 for advanced cancers?

Research on similar bispecific antibodies, like LY3434172, shows that targeting both PD-1 and PD-L1 can enhance T-cell activation and improve antitumor responses, suggesting potential effectiveness for ATG-101, which also targets PD-L1. ^{1 2 3 4 5}

What safety data exists for ATG-101 or similar bispecific antibodies in humans?

There is no specific safety data available for ATG-101, but bispecific antibodies like it are being tested in clinical trials for cancer treatment. These trials often focus on safety, and while some bispecific antibodies have shown promise, they can also have dose-limiting toxicities (side effects that prevent increasing the dose). ^{1 2 6 7 8}

What makes the drug ATG-101 unique for treating advanced cancers?

ATG-101 is a bispecific antibody that targets both PD-L1 and 4-1BB, which is unique because it not only blocks the PD-L1 pathway to help the immune system attack cancer cells but also stimulates 4-1BB to enhance T-cell activation, potentially offering a dual mechanism to fight cancer more effectively than treatments targeting only one of these pathways. ^{1 2 4 5 9}

Research Team

Eligibility Criteria

This trial is for adults with advanced solid tumors or mature B-cell Non-Hodgkin Lymphomas that have worsened after standard treatment, can't tolerate it, or have no suitable standard options. Participants must be expected to live at least 12 weeks and be in fairly good health (ECOG status 0-1). They should use birth control.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer has worsened despite treatment, or I can't tolerate standard treatments, and I'm expected to live at least 12 more weeks.

Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.

Exclusion Criteria

Pregnant or nursing females.

You have had allergic reactions in the past to drugs that are similar to ATG-101.

I don't have any lasting side effects from previous treatments, except for hair loss.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ATG-101 to determine the maximum tolerated dose

Cycle 1 (approximately 4 weeks)

Dose Expansion

Participants receive ATG-101 at the determined dose to further evaluate safety and efficacy

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• ATG-101 (Cancer Vaccine)

Trial Overview The study tests ATG-101, a new potential cancer drug. It's the first time this drug is being tried in humans (Phase I) to see how safe it is and how well it works against certain cancers that are either spreading (metastatic) or cannot be removed by surgery.

Participant Groups

Group I: Single experimental arm for ATG-101 Experimental Treatment 1 Intervention

Subjects with advanced or metastatic solid tumors and mature B-NHLs will be enrolled.

ATG-101 is already approved in China for the following indications:

Approved in China as ATG-101 for:

• Solid tumors and Mature B-cell Non-Hodgkin Lymphomas (under clinical development)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Northwestern University Chicago, IL

University of Colorado Hospital Boulder, CO

University of California San Francisco San Francisco, CA

Washington University School of Medicine in St. Louis Saint Louis, MO

More Trial Locations

Who Is Running the Clinical Trial?

Antengene Biologics Limited

Lead Sponsor

Trials

3

Recruited

240+

Findings from Research

FS118, a bispecific antibody targeting both LAG-3 and PD-L1, shows promise in overcoming resistance to PD-L1 therapies by enhancing T-cell activity and reducing immune suppression, demonstrating better efficacy than using single antibodies.

In mouse models, FS118 significantly suppressed tumor growth and revealed a unique mechanism where treatment led to decreased LAG-3 expression on T cells, suggesting a novel way to reinvigorate exhausted immune cells in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity. Kraman, M., Faroudi, M., Allen, NL., et al.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Bispecific antibodies, like Removab and Blincyto, have shown significant potential in immuno-oncology, leading to increased interest and investment from pharmaceutical companies.

Currently, over 30 bispecific molecules are in clinical trials, highlighting their growing role as immune effector cell engagers in cancer treatment, with promising strategies targeting various immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? Del Bano, J., Chames, P., Baty, D., et al.[2020]

A new bispecific fusion protein targeting both 4-1BB and PD-L1 has been developed to enhance the efficacy of cancer treatment while minimizing dose-limiting toxicities associated with single-agent 4-1BB agonists.

The study includes both preclinical and clinical data, indicating promising results for this first-in-class therapy in improving cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Converting Tumoral PD-L1 into a 4-1BB Agonist for Safer and More Effective Cancer Immunotherapy. Li, Z., Azar, JH., Rubinstein, MP.[2023]

The bispecific antibody BsPD-L1xrErbB2 effectively targets both PD-L1 and Her2 in tumor cells, demonstrating enhanced anti-tumor effects in mouse models of Her2-positive metastatic breast cancer compared to standard therapies.

The effectiveness of BsPD-L1xrErbB2 relies on CD8+ T lymphocytes and IFN-γ, indicating that it boosts the immune response against tumors by increasing the presence of these immune cells in the tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of ErbB2 and PD-L1 using a bispecific antibody to improve targeted anti-ErbB2 therapy. Mittal, D., Vijayan, D., Neijssen, J., et al.[2021]

References

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

A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. [2023]

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

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity. [2022]

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

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

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

A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer. [2018]

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

Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? [2020]

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

Converting Tumoral PD-L1 into a 4-1BB Agonist for Safer and More Effective Cancer Immunotherapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The state of the art of bispecific antibodies for treating human malignancies. [2023]

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

Blockade of ErbB2 and PD-L1 using a bispecific antibody to improve targeted anti-ErbB2 therapy. [2021]