Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Triple Negative Breast Neoplasms

Mesothelioma

Mesothelioma, Malignant

Carcinoma

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Hormones

Sacituzumab govitecan

Pembrolizumab

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

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.

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.

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.

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.

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

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.

AG-01 Compound

Ginette Serrero, PhD/DSC.

Katherine Tkaczuk, MD

Amelia Barkman, MHA/CCRP

Renee Mehra, MD

Paula Rosenblatt, MD

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).

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).

For dose escalation, model is an accelerated titration design-1-(3+3)

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

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

Exploratory outcome-To determine the serial GP88 blood levels using the available ELISA blood test while on treatment with the Anti-GP88 monoclonal antibody (AG01).

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.

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.

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.

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:

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.

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

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

Spots Global Cancer Trial Database for progranulin

Every month we try and update this database with for progranulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for progranulin

Every month we try and update this database with for progranulin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for progranulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.