ATG-101 for Advanced Cancers

(PROBE Trial)

No longer recruiting at 10 trial locations

Overseen By Doris Tao

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Antengene Biologics Limited

Must not be taking: 4-1BB agonists

Disqualifiers: CNS tumors, Active infection, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ATG-101 (a PD-L1/4-1BB bispecific antibody) for individuals with advanced or metastatic solid tumors and certain types of non-Hodgkin lymphomas, which are difficult to treat or have spread. The trial aims to assess the safety and effectiveness of ATG-101 as a first-time treatment in humans. Individuals with a confirmed solid tumor or mature B-cell non-Hodgkin lymphoma, who have not responded to or cannot tolerate standard treatments, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that ATG-101 is likely to be safe for humans?

Research shows that ATG-101 is designed to reduce potential harmful effects on the body, aiming to minimize side effects. This treatment is a bispecific antibody, a type of therapy tested in other cancer studies. However, specific safety information for ATG-101 is not yet available. As it is in Phase 1, this marks the first time it is being tested in humans. This phase focuses on assessing safety, so information about its tolerability remains limited. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for advanced cancers, like chemotherapy and radiation, work by attacking rapidly dividing cells, but this often affects healthy cells too, causing significant side effects. ATG-101 is different because it targets specific proteins on the surface of cancer cells, aiming to minimize harm to normal cells. Researchers are excited about ATG-101 because this targeted approach could potentially improve effectiveness and reduce side effects compared to current options. By zeroing in on cancer cells with precision, ATG-101 offers a promising new strategy for tackling tough-to-treat cancers.

What evidence suggests that ATG-101 might be an effective treatment for advanced cancers?

Research has shown that ATG-101 is a promising new treatment for advanced cancers. In this trial, participants will receive ATG-101, which functions in two ways: it blocks a protein called PD-L1, helping the immune system detect cancer, and it activates 4-1BB, enhancing the immune system's ability to fight tumors. This dual action aims to boost the body's natural defenses against cancer. Although ATG-101 is still under study, early findings suggest it could be effective, particularly for patients who don't respond well to other treatments. However, more data from human trials is needed to confirm its efficacy. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ATG-101

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.

How Is the Trial Designed?

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 United States, China for the following indications:

Approved in United States as ATG-101 for:

• Pancreatic cancer (Orphan Drug Designation)

Approved in China as ATG-101 for:

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

Who Is Running the Clinical Trial?

Antengene Biologics Limited

Lead Sponsor

Trials

3

Recruited

240+

Published Research Related to This Trial

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]

LY3434172, a bispecific antibody targeting both PD-1 and PD-L1, showed enhanced T-cell activation and antitumor activity in vitro compared to existing therapies that target these pathways individually.

In mouse models with human immune cells, LY3434172 demonstrated significantly stronger antitumor effects than either the anti-PD-1 or anti-PD-L1 antibodies alone, suggesting its potential as a novel cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Targeting of PD-1 and PD-L1 Enhances T-cell Activation and Antitumor Immunity. Kotanides, H., Li, Y., Malabunga, M., et al.[2021]

Bispecific antibodies (bsAbs) are being actively researched and tested in clinical trials for cancer treatment, targeting two different antigens to enhance therapeutic effects.

The review discusses the safety profiles and efficacy of various bsAbs, while also addressing challenges in their development and potential future directions for improving their use in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The state of the art of bispecific antibodies for treating human malignancies. Wang, S., Chen, K., Lei, Q., et al.[2023]

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]

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]

FS118, a bispecific antibody targeting LAG-3 and PD-L1, was well tolerated in a phase 1 study with 43 patients who had advanced cancer resistant to anti-PD-(L)1 therapy, showing no serious adverse events or dose-limiting toxicities.

The study demonstrated a disease control rate of 46.5%, with a higher rate of 54.8% in patients receiving doses of 1 mg/kg or greater, indicating potential efficacy in this difficult-to-treat population.

NCBI (Pubmed)

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. Yap, TA., LoRusso, PM., Wong, DJ., et al.[2023]

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]

The bispecific antibody (BsAb) designed to target both c-MET and PD-1 effectively induces degradation of c-MET in cancer cells and inhibits their growth, migration, and survival, demonstrating its potential as a cancer treatment.

In animal studies, BsAb significantly reduced tumor growth and chronic inflammation, suggesting it could enhance T cell activation and improve immune response against solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel bispecific c-MET/PD-1 antibody with therapeutic potential in solid cancer. Sun, ZJ., Wu, Y., Hou, WH., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04986865

NCT04986865 | A Study ATG-101 in Patients With ... This is a First-in-Human Phase I trial of ATG-101 in Patients with Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas.

2. prnewswire.com prnewswire.com/apac/news-releases/antengene-publishes-preclinical-paper-on-pd-l14-1bb-bispecific-antibody-atg-101-in-renowned-oncology-journal-cancer-research-302093184.html

Antengene Publishes Preclinical Paper on PD-L1/4-1BB ... ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38501978/

ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody ... However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04986865

A Study ATG-101 in Patients With Metastatic/Advanced ... A phase I trial of ATG-101, an investigational PD-L1×4-1BB bispecific antibody, in patients with advanced solid tumors and mature B cell non-Hodgkin lymphomas.

5. antengene.com antengene.com/static/upload/sofa/20220803/c86f415ab4ed658c6839b65ca317405e.pdf

c86f415ab4ed658c6839b65ca3... ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of advanced/metastatic solid tumors and B-cell non-.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02652-8/fulltext

1075TiP A phase I trial of ATG-101, an investigational PD- ... ATG-101 addresses these issues by enhancing the activity of 4-1BB agonism whilst reducing the potential of systemic toxicity through strategic engineering.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05490043

A Trial of ATG-101 in Patients With Metastatic/Advanced ... This is a First-in-Human Phase I trial of ATG-101 in Patients with Metastatic/Advanced Solid Tumors and Mature B-cell Non-Hodgkin Lymphomas. Dose Escalation ...

8. withpower.com withpower.com/trial/phase-1-lymphoma-9-2021-69cf3

ATG-101 for Advanced Cancers · Info for Participants There is no specific safety data available for ATG-101, but bispecific antibodies like it are being tested in clinical trials for cancer treatment.