AzTrials
AzTrials

Triple Negative Breast CancerPhase 1NCT05627960

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

A Phase 1 study testing AG-01 Compound in people with Triple Negative Breast Cancer and Hormone-Resistant Breast Cancer, run by A&G Pharmaceutical Inc. at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AG-01 Compound
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
1 siteUnited States
Study dates
14 Feb 2022to Nov 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent/authorization is obtained prior to conducting any study-specific screening procedures.
  • 18 years of age or older.
  • Histologic or cytologic diagnosis of advanced cancer.
  • Radiographic evidence of at least 1 measurable metastatic lesion per RECIST 1.1 criteria.
  • 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.
  • 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.
Show all 19Show fewer
  • At least 4 weeks after the last dose of chemotherapy or radiation therapy; 6 weeks for mitoxantrone or mitomycin therapy.
  • ECOG performance status must be ≤2 (Appendix A).
  • 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)
  • 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.
  • Men and women of all ethnic groups are eligible for this trial.
  • Females at reproductive age must have a negative urine pregnancy test prior to entry to this study.
  • 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.
  • Life expectancy is greater than 12 weeks.
  • 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.
  • 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.
  • 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.
  • Mesothelioma patients who have received at least 1 SOC therapy for metastatic/recurrent mesothelioma per NCCN recommendations or not a candidate for SOC therapy.

Who cannot join

  • 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.
  • Uncontrolled or untreated CNS metastases and treated CNS metastases are allowed, as long as the patient is clinically stable.
  • Presence carcinomatous meningeal involvement.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ginette Serrero, PhD/DSC. contact

(410)884-4100 ext. 14

gserrero@agpharma.com

Katherine Tkaczuk, MD contact

(410) 328-7394

ktkaczuk@umm.edu

United States1 site, 1 recruiting

  • University of Maryland Greenebaum Comprehensive Cancer Center

    Baltimore, Maryland, 21201

    Katherine Tkaczuk, MD, 410-328-7394, ktkaczuk@umm.edu

    Amelia Barkman, MHA/CCRP, 443-825-2456, Amelia.Barkman@umm.edu

    Recruiting

Other trials in United States

About this study

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

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).

Read the 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).

Being tested
AG-01 Compound
Keywords
Progranulin, Advanced solid malignancies, Phase 1, Anti-Progranulin antibody, Advanced solid tumors, Breast Cancer, Lung Cancer, Mesothelioma
Medical subject headings
Triple Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Mesothelioma, Breast Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AG-01 CompoundDrug

    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.

Study groups in NCT05627960
Study groupRoleWhat they receive
AG-01 treated group phase 1AExperimentalFor 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.
Receives: Drug: AG-01 Compound
AG-01 1B triple negative breast cancer treated groupExperimentalTNBC 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.
Receives: Drug: AG-01 Compound
AG-01 1B Hormone-resistant breast cancerExperimentalHormone-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.
Receives: Drug: AG-01 Compound
AG-01 1B NSCLCExperimentalSubjects 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.
Receives: Drug: AG-01 Compound
AG-01-1B mesotheliomaExperimentalSubjects with mesothelioma who received at least 1 SOC therapy for metastatic/recurrent mesothelioma per NCCN guidelines or not a candidate for SOC therapy.
Receives: Drug: AG-01 Compound

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Determine the MTD and/or MAD of anti GP88 monoclonal antibody (AG-01) in subjects with advanced/refractory solid tumor malignancies for which no effective therapies exist.

    Measured: 28 days during 1st cycle

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

    To evaluate the antitumor activity of AG-01 monoclonal antibody as assessed by ORR defined as complete response (CR), partial response (PR), stable disease >24 weeks (SD) (CR+PR+ SD) based on RECIST v1.1 in subjects with TNBC, ER+ hormone resistant Breast Cancer, NSCLCA and mesothelioma.

    Each cohort will be assessed separately for response.

    Measured: Every 56 Days

Secondary outcomes (5)

  1. Recommended phase 2 dose (RP2D) of AG-01-Phase 1A

    During 1A portion accelerated titration (1pt/dose) design will be utilized to guide dose progression and estimation of the maximum tolerated dose MTD and/or maximum administered dose (MAD) (1). Once treatment related DLT occurs, this cohort will be expanded to 3+3 design, and all subsequent cohorts will follow the 3+3 design.

    First dose/cohort level subjects will be monitored for 28 days from the D1 of the 1st infusion of AG01 (2 doses, D 1 and D15 of AG01) before the dose is escalated to the next dose level without expansion of cohort and assuming no DLTs during this time.

    Measured: 28 days or 1cycle

  2. Safety and tolerability of AG-01

    Subjects will be monitored for emergence of any adverse events; with physical exams, laboratory assessments, ECOG PS, Vital signs, changes in weight, clinical symptoms. Adverse events will be assessed via CTACE V 5.0 on ongoing basis in Phase 1A and 1B:

    Measured: While receiving AG-01 for 56 days and for 30 days after the last dose of the study drug (day 86)

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

    Blood samples will be collected collected in cycles 1 and 2, End of Treatment and 30 days post-treatment, per study schedule to determine AG01 drug levels and PK profile.

    Measured: 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).

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

    Response to treatment with AG-01 will be assessed with tumor imaging (CTs/MRIs/Bone scan-as applicable) every 56 days, response will be assessed via RECIST 1.1

    Measured: While receiving AG-01 treatment, at day 56

  5. Anti-drug antibodies (ADA) to AG-01

    ADA blood samples will be collected prior to AG-01 administration on Days 1, 15, 29, and 43 with blood sampling following the described time frame and tested via immunoassay for presence anti-AG01 antibodies

    Measured: Day 1 (cycle1 first dose) Day 15 (cycle 1 second dose), day 29 (Cycle 2 first dose), day 43 (cycle 2 second dose), Day 57 (end of treatment),and Day 87 (30 days post end of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2022
  2. Study start14 Feb 2022
  3. Primary completionJun 2026 (estimated)
  4. Study completionNov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
For dose escalation, model is an accelerated titration design-1-(3+3)
Masking
None (open label)
Enrolment
77 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05627960
Sponsor's protocol ID
GCC1950
Status last verified
Nov 2022
First submitted
16 Mar 2022
Last updated
28 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Serrero G. Potential of Theranostic Target Mining in the Development of Novel Diagnostic and Therapeutic Products in Oncology: Progranulin/GP88 as a Therapeutic and Diagnostic Target for Breast and Lung Cancers. Rinsho Byori. 2016 Nov;64(11):1296-1309.

    PubMed 30695312

  • Tkaczuk KHR, Hawkins D, Yue B, Hicks D, Tait N, Serrero G. Association of Serum Progranulin Levels With Disease Progression, Therapy Response and Survival in Patients With Metastatic Breast Cancer. Clin Breast Cancer. 2020 Jun;20(3):220-227. doi: 10.1016/j.clbc.2019.11.010. Epub 2019 Dec 5.

    PubMed 31928925

  • Koo DH, Do IG, Oh S, Lee YG, Kim K, Sohn JH, Park SK, Yang HJ, Jung YS, Park DI, Jeong KU, Kim HO, Kim H, Serrero G, Chun HK; KBSMC Colorectal Cancer Team. Prognostic Value of Progranulin in Patients with Colorectal Cancer Treated with Curative Resection. Pathol Oncol Res. 2020 Jan;26(1):397-404. doi: 10.1007/s12253-018-0520-7. Epub 2018 Oct 30.

    PubMed 30378010

  • Greither T, Steiner T, Bache M, Serrero G, Otto S, Taubert H, Eckert AW, Kappler M. GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients. Biology (Basel). 2021 May 4;10(5):400. doi: 10.3390/biology10050400.

    PubMed 34064411

  • Guha R, Yue B, Dong J, Banerjee A, Serrero G. Anti-progranulin/GP88 antibody AG01 inhibits triple negative breast cancer cell proliferation and migration. Breast Cancer Res Treat. 2021 Apr;186(3):637-653. doi: 10.1007/s10549-021-06120-y. Epub 2021 Feb 22.

    PubMed 33616772

  • Serrero G, Hawkins DM, Bejarano PA, Ioffe O, Tkaczuk KR, Elliott RE, Head JF, Phillips J, Godwin AK, Weaver J, Hicks D, Yue B. Determination of GP88 (progranulin) expression in breast tumor biopsies improves the risk predictive value of the Nottingham Prognostic Index. Diagn Pathol. 2016 Aug 8;11(1):71. doi: 10.1186/s13000-016-0520-4.

    PubMed 27501955

  • Edelman MJ, Feliciano J, Yue B, Bejarano P, Ioffe O, Reisman D, Hawkins D, Gai Q, Hicks D, Serrero G. GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol. 2014 Sep;45(9):1893-9. doi: 10.1016/j.humpath.2014.05.011. Epub 2014 Jun 5.

    PubMed 25033727

  • Serrero G, Hawkins DM, Yue B, Ioffe O, Bejarano P, Phillips JT, Head JF, Elliott RL, Tkaczuk KR, Godwin AK, Weaver J, Kim WE. Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma. Breast Cancer Res. 2012 Feb 8;14(1):R26. doi: 10.1186/bcr3111.

    PubMed 22316048

  • Arechavaleta-Velasco F, Perez-Juarez CE, Gerton GL, Diaz-Cueto L. Progranulin and its biological effects in cancer. Med Oncol. 2017 Nov 7;34(12):194. doi: 10.1007/s12032-017-1054-7.

    PubMed 29116422

  • Abrhale T, Brodie A, Sabnis G, Macedo L, Tian C, Yue B, Serrero G. GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells. BMC Cancer. 2011 Jun 9;11:231. doi: 10.1186/1471-2407-11-231.

    PubMed 21658239

  • Wong NC, Cheung PF, Yip CW, Chan KF, Ng IO, Fan ST, Cheung ST. Antibody against granulin-epithelin precursor sensitizes hepatocellular carcinoma to chemotherapeutic agents. Mol Cancer Ther. 2014 Dec;13(12):3001-12. doi: 10.1158/1535-7163.MCT-14-0012. Epub 2014 Sep 24.

    PubMed 25253787

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-01 Compound in people with Triple Negative Breast Cancer and Hormone-Resistant Breast Cancer, run by A&G Pharmaceutical Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ginette Serrero, PhD/DSC. ((410)884-4100 ext. 14, gserrero@agpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) and/or Maximum Administered Dose (MAD) (time frame: 28 days during 1st cycle). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05627960, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in