Trial Title:
First in Human Phase 1 Study of AG01 Anti-Progranulin/GP88 Antibody in Advanced Solid Tumor Malignancies
NCT ID:
NCT05627960
Condition:
Triple Negative Breast Cancer
Hormone-Resistant Breast Cancer
Non Small Cell Lung Cancer
Mesothelioma
Conditions: Official terms:
Breast Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Triple Negative Breast Neoplasms
Mesothelioma
Mesothelioma, Malignant
Conditions: Keywords:
Progranulin
Advanced solid malignancies
Phase 1
Anti-Progranulin antibody
Advanced solid tumors
Breast Cancer
Lung Cancer
Mesothelioma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
For dose escalation, model is an accelerated titration design-1-(3+3)
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AG-01 Compound
Description:
Phase 1A dose escalation study: enrolled subjects with advanced solid tumors will receive
AG-01 compound at various doses.
Phase 1B patients will be treated with AG-01 at the RP2D.
Arm group label:
AG-01 1B Hormone-resistant breast cancer
Arm group label:
AG-01 1B NSCLC
Arm group label:
AG-01 1B triple negative breast cancer treated group
Arm group label:
AG-01 treated group phase 1A
Arm group label:
AG-01-1B mesothelioma
Summary:
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).
Detailed description:
PGRN/GP88 is an 88 kilodalton glycoprotein produced by cells of epithelial or mesenchymal
origin. It is an autocrine growth factor, which is overexpressed in several human cancers
including breast and ovarian cancer, multiple myeloma, prostate cancer, non small cell as
well as other tumors. High GP88 expression is associated with the malignant phenotype,
increased proliferation and survival associated with drug resistance to some currently
used therapeutic agents. Pathological studies have shown that PGRN/GP88 is an independent
prognostic factor in several cancers including breast, non-small cell lung carcinoma,
prostate and digestive cancers. High GP88 expression in tumor tissues is associated with
decreased disease-free survival and increased mortality. In addition, in stage 4 breast
cancer patients, high circulating level of PGRN/GP88 is associated with decreased overall
survival.
This study will enroll patients with relapsed/refractory solid tumor malignancies (1A)
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. In 1B portion
of the study patients with triple negative breast cancer, hormone resistant breast
cancer, non small cell lung cancer and mesothelioma will be accrued. The treatment period
(cycle) will consist of 28-day cycles, the AGO1 will be infused every 14 days. The dosing
schedule/frequency of treatments for subjects in the dose escalation portion (1A) will be
the same as for subjects in the expansion portion (1B).
Criteria for eligibility:
Criteria:
Inclusion 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:
Absolute neutrophil count ≥ 1,000/uL Platelets ≥ 100,000/µL Total bilirubin WNL per
Institution ULN AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional ULN Creatinine ≤1.2
mg/dL Clearance ≥50ml/min (Cockcroft-Gault)
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.
Exclusion Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Maryland Greenebaum Comprehensive Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katherine Tkaczuk, MD
Phone:
410-328-7394
Email:
ktkaczuk@umm.edu
Contact backup:
Last name:
Amelia Barkman, MHA/CCRP
Phone:
443-825-2456
Email:
Amelia.Barkman@umm.edu
Investigator:
Last name:
Katherine Tkaczuk, MD
Email:
Principal Investigator
Investigator:
Last name:
Renee Mehra, MD
Email:
Sub-Investigator
Investigator:
Last name:
Paula Rosenblatt, MD
Email:
Sub-Investigator
Start date:
February 14, 2022
Completion date:
November 2026
Lead sponsor:
Agency:
A&G Pharmaceutical Inc.
Agency class:
Industry
Collaborator:
Agency:
University of Maryland Greenebaum Cancer Center
Agency class:
Other
Source:
A&G Pharmaceutical Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05627960
