Astsaturov on the Phase 1 Study of LP-184 in Advanced Solid Tumors

Igor Astsaturov, MD, PhD, associate professor in the Department of Hematology/Oncology and co-director of The Marvin and Concetta Greenberg Pancreatic Cancer Institute at Fox Chase Cancer Center, discusses the planned phase 1 trial of LP-184 in multiple advanced solid tumors and central nervous system (CNS) cancers, including pancreatic cancer.

The first-in-human, phase 1a trial is using a Bayesian design to evaluate LP-184 across various tumor types. The goals of the study are to assess the safety and tolerability of escalating doses of LP-184 to determine the maximum tolerated dose in patients with advanced pancreatic cancer, recurrent high-grade gliomas/glioblastoma, metastatic brain and CNS cancers, as well as other solid tumors with DNA damage response deficiencies.

Transcription:

0:10 | When we take a new drug to clinical testing, we have to be careful in terms of what dose can be tolerated, so it usually starts with phase 1, which is essentially to determine the drugs safety and tolerability, how much can be given, what are the potential [adverse] effects and toxicities. From prior experiences with other cancer trials of these classes of drugs, there are some known toxicities which we are aware of, and it has to go through a slow process of gradual dose-escalation. This is what the idea is.

0:54 | We also applied a rather smart design, which is called the Bayesian design. Essentially, it's a way to move progressively and faster into higher, more effective doses of the chemotherapy agent while selecting patients who are more likely to be deriving some benefit. We will be looking for patients who have mutations in their cancers in the DNA repair pathway.

1:22 | We will also be retrospectively correlating the responses or any clinical effects with the expression of this rather unique enzyme called PTGR1, prostaglandin reductase. These are fundamental observations that will hopefully help us to develop this drug fully when it goes through a more advanced phase of testing, like phase 2 and phase 3, subsequently.