RECRUITING

First in Human Phase 1 Study of AG01 Anti-Progranulin/GP88 Antibody in Advanced Solid Tumor Malignancies

Conditions

Triple Negative Breast Cancer Hormone-Resistant Breast Cancer Non Small Cell Lung Cancer Mesothelioma Progranulin Advanced solid malignancies Phase 1 Anti-Progranulin antibody Advanced solid tumors Breast Cancer Lung Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a first in human phase 1 study of AG01 an anti-Progranulin/Glycoprotein88 (PGRN/GP88) antibody in patients with advanced solid tumors. AG01 is a recombinant monoclonal antibody expressed in a CHO production cell line. The antibody AG01 binds to human PGRN/GP88, expressed on cancer cells. This study will have a dose escalation portion (1A) to evaluate maximum tolerated dose (MTD) and/or maximum administered dose (MAD), the safety and tolerability of AG01treatment before the dose expansion portion (1B) of the study is initiated. The dose escalation portion of this study (1A) will also be used to determine the recommended phase 2 dose (RP2D) of AG01 antibody to be evaluated in the cohort expansion portion (1B).

Official Title

FIH Phase 1A /1B Study of AG01 Antibody Against Progranulin/GP88 in Advanced Solid Tumor Malignancies With Expansion Cohorts in Advanced Triple Negative Breast Ca, Hormone Resistant Breast Ca, Non Small Cell Lung Cancer and Mesothelioma

Quick Facts

Study Start:2022-02-14

Study Completion:2026-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05627960

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent/authorization is obtained prior to conducting any study-specific screening procedures. 2. 18 years of age or older. 3. Histologic or cytologic diagnosis of advanced cancer. 4. Radiographic evidence of at least 1 measurable metastatic lesion per RECIST 1.1 criteria. 5. Patients with relapsed/refractory solid tumor malignancies who failed one or more standard chemotherapy or targeted therapy regimens per SOC guidelines such as NCCN guidelines and for whom no standard therapy exists (Phase 1A). No GP88 expression pre-required for phase 1A. 6. For phase 1B, patients must have GP88 tissue tumor tissue expression of 1+, 2+ or 3+ by IHC, archival tumor tissue will be used whenever possible. If no archival tissue is available, subject will be asked to consent to a study specific tumor biopsy for GP88 testing (phase1B). Patients who do not have archival tissue available for the dose expansion cohort (1B) will not be exposed to significant risk procedure to obtain tissue and may still be eligible for the study, after discussion with the Sponsor and Medical Monitor. 7. At least 4 weeks after the last dose of chemotherapy or radiation therapy; 6 weeks for mitoxantrone or mitomycin therapy. 8. ECOG performance status must be ≤2 (Appendix A). 9. Adequate hepatic, renal, and bone marrow function: 10. All study participants (male and female) with reproductive potential must practice highly effective methods of contraception (failure rate \<1% annually) while on this study and for 90 days after completion of study therapy. 11. Men and women of all ethnic groups are eligible for this trial. 12. Females at reproductive age must have a negative urine pregnancy test prior to entry to this study. 13. 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. 14. Life expectancy is greater than 12 weeks. 15. Subjects with triple negative breast cancer (TNBC) cohort must have received 1 or more standard of care (SOC) or targeted therapies for metastatic TNBC. If PD(L)1-positive, must have received a combination of chemotherapy and a PD (L)-1 agent (Atezolizumab or 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. is FDA approved for treatment of advanced TNBC. Prior exposure to Sacituzumab Govitecan ADC therapy does not preclude eligibility in the current study. 16. Subjects with Cohort 2-Breast Cancer ER and/or PR positive, hormone-resistant breast cancer who received 1 or more hormonal (HT) therapies or HT/CD4/6 kinase inhibitor or HT/MTOR inhibitor for treatment of metastatic breast cancer are eligible. If the tumor has known PIK3CA mutation, HT/Alpelisib combination should be considered unless not a candidate for this therapy. 17. Subjects with metastatic/recurrent NSCLCA who failed 2 or more SOC therapies, including platinum-based chemotherapy and an anti-PD (L) -1 agent (sequentially or consecutively). Patients 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. 18. Mesothelioma patients who have received at least 1 SOC therapy for metastatic/recurrent mesothelioma per NCCN recommendations or not a candidate for SOC therapy.	1. Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias not well controlled with medication, myocardial infarction within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements. 2. Uncontrolled or untreated CNS metastases and treated CNS metastases are allowed, as long as the patient is clinically stable. 3. Presence carcinomatous meningeal involvement. 4. Patients may not be receiving any other investigational agents, or have participated in any investigational drug study \< 28 days prior to starting on the current study. 5. Since the teratogenic potential of AG01 is currently unknown, females who are pregnant or lactating are excluded. 6. 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. 7. History of any other malignancies in the last 2 years except for in-situ cancer, basal or squamous cell skin cancer treated with curative intent.

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent/authorization is obtained prior to conducting any study-specific screening procedures.
2. 18 years of age or older.
3. Histologic or cytologic diagnosis of advanced cancer.
4. Radiographic evidence of at least 1 measurable metastatic lesion per RECIST 1.1 criteria.
5. Patients with relapsed/refractory solid tumor malignancies who failed one or more standard chemotherapy or targeted therapy regimens per SOC guidelines such as NCCN guidelines and for whom no standard therapy exists (Phase 1A). No GP88 expression pre-required for phase 1A.
6. For phase 1B, patients must have GP88 tissue tumor tissue expression of 1+, 2+ or 3+ by IHC, archival tumor tissue will be used whenever possible. If no archival tissue is available, subject will be asked to consent to a study specific tumor biopsy for GP88 testing (phase1B). Patients who do not have archival tissue available for the dose expansion cohort (1B) will not be exposed to significant risk procedure to obtain tissue and may still be eligible for the study, after discussion with the Sponsor and Medical Monitor.
7. At least 4 weeks after the last dose of chemotherapy or radiation therapy; 6 weeks for mitoxantrone or mitomycin therapy.
8. ECOG performance status must be ≤2 (Appendix A).
9. Adequate hepatic, renal, and bone marrow function:
10. All study participants (male and female) with reproductive potential must practice highly effective methods of contraception (failure rate \<1% annually) while on this study and for 90 days after completion of study therapy.
11. Men and women of all ethnic groups are eligible for this trial.
12. Females at reproductive age must have a negative urine pregnancy test prior to entry to this study.
13. 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.
14. Life expectancy is greater than 12 weeks.
15. Subjects with triple negative breast cancer (TNBC) cohort must have received 1 or more standard of care (SOC) or targeted therapies for metastatic TNBC. If PD(L)1-positive, must have received a combination of chemotherapy and a PD (L)-1 agent (Atezolizumab or 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. is FDA approved for treatment of advanced TNBC. Prior exposure to Sacituzumab Govitecan ADC therapy does not preclude eligibility in the current study.
16. Subjects with Cohort 2-Breast Cancer ER and/or PR positive, hormone-resistant breast cancer who received 1 or more hormonal (HT) therapies or HT/CD4/6 kinase inhibitor or HT/MTOR inhibitor for treatment of metastatic breast cancer are eligible. If the tumor has known PIK3CA mutation, HT/Alpelisib combination should be considered unless not a candidate for this therapy.
17. Subjects with metastatic/recurrent NSCLCA who failed 2 or more SOC therapies, including platinum-based chemotherapy and an anti-PD (L) -1 agent (sequentially or consecutively). Patients 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.
18. Mesothelioma patients who have received at least 1 SOC therapy for metastatic/recurrent mesothelioma per NCCN recommendations or not a candidate for SOC therapy.

1. Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmias not well controlled with medication, myocardial infarction within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
2. Uncontrolled or untreated CNS metastases and treated CNS metastases are allowed, as long as the patient is clinically stable.
3. Presence carcinomatous meningeal involvement.
4. Patients may not be receiving any other investigational agents, or have participated in any investigational drug study \< 28 days prior to starting on the current study.
5. Since the teratogenic potential of AG01 is currently unknown, females who are pregnant or lactating are excluded.
6. 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.
7. History of any other malignancies in the last 2 years except for in-situ cancer, basal or squamous cell skin cancer treated with curative intent.

Contacts and Locations

Study Contact

Ginette Serrero, PhD/DSC.

CONTACT

(410)884-4100

gserrero@agpharma.com

Katherine Tkaczuk, MD

CONTACT

(410) 328-7394

ktkaczuk@umm.edu

Principal Investigator

Katherine Tkaczuk, MD

PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Study Locations (Sites)

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201

United States

Collaborators and Investigators

Sponsor: A&G Pharmaceutical Inc.

Katherine Tkaczuk, MD, PRINCIPAL_INVESTIGATOR, University of Maryland, Baltimore

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-14

Study Completion Date2026-11

Study Record Updates

Study Start Date2022-02-14

Study Completion Date2026-11

Terms related to this study

Keywords Provided by Researchers

Progranulin
Advanced solid malignancies
Phase 1
Anti-Progranulin antibody
Advanced solid tumors
Breast Cancer
Lung Cancer
Mesothelioma

Additional Relevant MeSH Terms

Triple Negative Breast Cancer
Hormone-Resistant Breast Cancer
Non Small Cell Lung Cancer
Mesothelioma