What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include monoclonal antibodies, chemotherapy, and immune checkpoint inhibitors. Monoclonal antibodies like AG01 can cause side effects such as infusion reactions, fatigue, and potential immune-related adverse events. Chemotherapy often leads to nausea, vomiting, neutropenia, and fatigue. Immune checkpoint inhibitors, such as pembrolizumab and atezolizumab, can result in immune-related toxicities including pneumonitis, colitis, hepatitis, and endocrinopathies. These treatments aim to manage the disease but come with a range of potential side effects that need to be monitored closely.

What prior FDA approvals exist?

Several FDA-approved treatments for Non-Small Cell Lung Cancer (NSCLC) involve monoclonal antibodies and immune checkpoint inhibitors. Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy when combined with chemotherapy, improving overall survival (OS) and progression-free survival (PFS) in patients with advanced NSCLC. Atezolizumab, an anti-PD-L1 antibody, combined with chemotherapy and bevacizumab, has also been approved for advanced nonsquamous NSCLC, demonstrating improved OS and PFS. These treatments highlight the potential of antibody-based therapies in managing NSCLC, similar to the investigational AG01 anti-Progranulin/Glycoprotein88 antibody.

What other types of research exist?

Promising alternatives to AG01 for NSCLC patients include PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab. These immune checkpoint inhibitors have shown efficacy in clinical trials and are approved for use in advanced NSCLC. Additionally, novel monoclonal antibodies like the anti-AMACR mAb G8, which targets AMACR-related cancers, may also be considered as potential alternatives.

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Monoclonal Antibodies

AG-01 Antibody Therapy for Advanced Cancers

Q: What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors and ALK inhibitors, work by specifically targeting and inhibiting the function of proteins that are involved in the growth and survival of cancer cells. Immunotherapies, such as PD-1/PD-L1 inhibitors, enhance the body's immune response against cancer cells by blocking the proteins that prevent immune cells from attacking the tumor. The AG01 anti-Progranulin/Glycoprotein88 antibody is a type of targeted therapy that binds to specific proteins expressed on cancer cells, potentially inhibiting their growth. These mechanisms are crucial for NSCLC patients as they offer more personalized and effective treatment options, often with fewer side effects compared to traditional chemotherapy.

Phase 1

Recruiting

Led By Katherine Tkaczuk, MD

Research Sponsored by A&G Pharmaceutical Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Males with partners at reproductive age must use highly effective birth control methods to prevent partners' pregnancy while on study and for 90 days after completion of study treatments

ECOG performance status must be ≤2 (Appendix A)

Must not have

Since the teratogenic potential of AG01 is currently unknown, females who are pregnant or lactating are excluded

Males and females unable to adhere to abstinence or use highly effective methods of contraception (annual failure rate < 1%) to prevent study subjects' pregnancy or study subjects' partner pregnancy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 (cycle1 first dose), day 4, day 8, day 15 (cycle 1 second dose), day 29 (cycle 2 first dose), day 43 (cycle 2 second dose), day 46, day 50, day 57 (end of treatment) and day 87 (30 days post end of treatment).

Awards & highlights

No Placebo-Only Group

Summary

This trial tests AG01, a protein that targets PGRN/GP88 on cancer cells, in patients with advanced cancers who haven't responded to other treatments. The goal is to see if AG01 can help control cancer growth by binding to PGRN/GP88. AG01 is a treatment that has been shown to reduce the growth and spread of certain cancer cells.

Who is the study for?

This trial is for adults with advanced solid tumors who have failed standard treatments. It includes those with specific types of lung, breast, and mesothelioma cancers. Participants must have measurable metastatic lesions, be in a stable condition, and use effective contraception. Those with certain recent malignancies or uncontrolled illnesses are excluded.

What is being tested?

AG01, an anti-Progranulin/Glycoprotein88 antibody designed to target cancer cells, is being tested for safety and the maximum tolerated dose in phase 1A. Phase 1B will expand on this to find the optimal dose for future studies based on participants' responses.

What are the potential side effects?

As AG01 is a new drug being tested for the first time in humans, potential side effects are not yet fully known but may include typical reactions related to monoclonal antibodies such as infusion reactions, immune-related issues, and organ inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am using effective birth control to prevent pregnancy during and 90 days after the study.

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I am able to care for myself and perform daily activities.

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I have mesothelioma and have tried at least one standard treatment or cannot undergo standard treatments.

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My liver, kidney, and bone marrow are functioning well according to specific blood test results.

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I am of childbearing age and have a negative pregnancy test.

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My cancer is confirmed to be advanced through testing.

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My cancer has not responded to standard treatments.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant or breastfeeding.

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I am using or willing to use effective birth control methods.

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I do not have any severe illnesses that could interfere with the study.

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My cancer has spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 (cycle1 first dose), day 4, day 8, day 15 (cycle 1 second dose), day 29 (cycle 2 first dose), day 43 (cycle 2 second dose), day 46, day 50, day 57 (end of treatment) and day 87 (30 days post end of treatment).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 (cycle1 first dose), day 4, day 8, day 15 (cycle 1 second dose), day 29 (cycle 2 first dose), day 43 (cycle 2 second dose), day 46, day 50, day 57 (end of treatment) and day 87 (30 days post end of treatment).

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 (cycle1 first dose), day 4, day 8, day 15 (cycle 1 second dose), day 29 (cycle 2 first dose), day 43 (cycle 2 second dose), day 46, day 50, day 57 (end of treatment) and day 87 (30 days post end of treatment). for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Antitumor Activity of AG-01 by Overall Response Rate (ORR)

Maximum Tolerated Dose (MTD) and/or Maximum Administered Dose (MAD)

Secondary study objectives

Anti-drug antibodies (ADA) to AG-01

Pharmacokinetic (PK) profile of AG-01-1A

Preliminary anti-tumor activity of the AG-01 in subjects with refractory/advanced solid tumor malignancies (1A and 1B).

+2 more

Other study objectives

Serial Glycoprotein88 (GP-88) blood levels

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: AG-01-1B mesotheliomaExperimental Treatment1 Intervention

Subjects with mesothelioma who received at least 1 SOC therapy for metastatic/recurrent mesothelioma per NCCN guidelines or not a candidate for SOC therapy.

Group II: AG-01 treated group phase 1AExperimental Treatment1 Intervention

For dose escalation, subjects will be treated with increasing doses of AG01 from 1 mg/kg to 8 mg/kg. The duration of each treatment cycle is 28 days with two infusions of AG01 every 14 days.

Group III: AG-01 1B triple negative breast cancer treated groupExperimental Treatment1 Intervention

TNBC is defined as ER and/or PR \< 1% by IHC, HER2 \<3+ by IHC and/or FISH negative, subjects must have received 1 or more standard of care (SOC) therapies for metastatic TNBC. If PD(L)1-positive, must have received a combination of chemotherapy and a PD (L)-1 agent (Pembrolizumab), unless not a candidate for these therapies If gBRCA 1 or 2 mutation is present, must have received SOC therapies including a PARPi, unless not a candidate for these therapies. Sacituzumab Govitecan ADC is FDA approved for treatment of advanced TNBC, prior exposure to this therapy does not preclude eligibility in the current study.

Group IV: AG-01 1B NSCLCExperimental Treatment1 Intervention

Subjects with metastatic/recurrent NSCLCA failed 2 or more SOC therapies, including platinum-based chemotherapy and an anti-PD (L) -1 agent (sequentially or consecutively), Subjects with sensitizing mutations/alterations/rearrangements are eligible if received 1 or more SOC agent/s targeting these mutations unless not a candidate for these therapies.

Group V: AG-01 1B Hormone-resistant breast cancerExperimental Treatment1 Intervention

Hormone-resistant breast cancer is defined as, ER and/or PR \>1%, HER2 \<3+ by IHC and/or FISH negative, received 1 or more hormonal (HT) therapies or HT/CD4/6 kinase inhibitor or HT/MTOR inhibitor for treatment of metastatic breast cancer. If the tumor has known PIK3CA mutation, HT/Alpelisib combination should be considered unless not a candidate for this therapy.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies and immunotherapies. Targeted therapies, such as EGFR inhibitors and ALK inhibitors, work by specifically targeting and inhibiting the function of proteins that are involved in the growth and survival of cancer cells. Immunotherapies, such as PD-1/PD-L1 inhibitors, enhance the body's immune response against cancer cells by blocking the proteins that prevent immune cells from attacking the tumor. The AG01 anti-Progranulin/Glycoprotein88 antibody is a type of targeted therapy that binds to specific proteins expressed on cancer cells, potentially inhibiting their growth. These mechanisms are crucial for NSCLC patients as they offer more personalized and effective treatment options, often with fewer side effects compared to traditional chemotherapy.

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities.Smoking history as a predictive factor of treatment response in advanced non-small-cell lung cancer: a systematic review.