Pharmacology & human Phase 1 safety & dose escalation studies using anti-GP88 in aggressive breast cancer

NIH RePORTER · NIH · R44 · $1,062,115 · view on reporter.nih.gov ↗

Abstract

In 2017, ~200,000 new cases of breast cancer (BC) and ~40,000 related deaths are expected in the US. ~30,000 of these are patients with aggressive triple negative BC (TNBC) or anti-estrogen/aromatase inhibitor resistant (AE/AI) BC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapy. A new approach that benefits these patients and provides increased life expectancy needs to be developed. We have identified GP88, a glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumors. GP88 is found in BC but not in normal breast tissue. There is compelling biological and clinical evidence to suggest that GP88 can be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE/AI BC patients. We have developed a tissue test to identify patients with tumors expressing GP88 and an anti-GP88 (AG1) to block the action of GP88 on tumor tissues to a) inhibit tumor growth and b) increase the efficacy of current BC drugs. We have safety and efficacy data in animals and will in our Phase 1 develop a dosing strategy in mice before moving into human studies as part of the Phase 2. Additionally, a blood test has been developed to monitor patients while on treatment. Using AG1 as the therapy with two companion diagnostic tests, we will carry out a phase IA/B clinical trial in humans to determine safety of AG1 manufactured under GMP in the Phase 2 and will collect tumor tissue and blood on all patients to evaluate for GP88 expression (tissue) and concentration (blood).

Key facts

NIH application ID
10245772
Project number
4R44CA224718-02
Recipient
A AND G PHARMACEUTICAL, INC.
Principal Investigator
Ginette Serrero
Activity code
R44
Funding institute
NIH
Fiscal year
2020
Award amount
$1,062,115
Award type
4N
Project period
2018-09-01 → 2023-02-28