Lisata Therapeutics Inc (NASDAQ:LSTA) chief medical officer Kristen Buck joined Proactive to discuss the company’s new research collaboration with Haystack Oncology which will evaluate the efficacy of its drug candidate certepetide as a therapy for pancreatic cancer.
She detailed the collaboration, which will leverage Haystack's minimal residual disease (MRD) technology to detect circulating tumor DNA in blood, which can indicate cancer recurrence or progression.
This technology will play a crucial role in Lisata’s ASCEND trial, which is set to report results in the fourth quarter of this year, Buck said.
Proactive: Lisata announced a research collaboration with Haystack Oncology to evaluate the efficacy of certepetide. Can you start by reminding us about certepetide and what it's targeted at?
Kristen Buck: Certepetide is a nine amino acid cyclic peptide. It's a small molecule. It's given over a one-minute IV push, and its job is to target two specific up-regulated receptors on solid tumors. By doing so, it selectively targets and penetrates solid tumors, allowing more anti-cancer therapy to get into the tumors and hopefully lead to better outcomes.
What are some of the challenges in the development of anti-cancer therapies for tumors like pancreatic tumors?
Pancreatic cancer is one of the most difficult to treat solid tumors. It has a hostile tumor microenvironment, which evades our immune system. Also, the location of pancreatic cancer is often in the retroperitoneum, which often limits its detection, and patients often have advanced stages of the disease before they have symptoms. Lastly, pancreatic cancer has a dense stromal barrier that surrounds the tumor, so whereas typical chemotherapy tries to get in, it doesn't because of this barrier. And so ,giving more chemotherapy often doesn't result in better outcomes, rather significant off-target effects.
Can you tell us more about Haystack Oncology and about the collaboration itself?
Yes, we are extremely excited to have a research collaboration with Haystack Oncology, which is a Quest Diagnostics company. Haystack has a highly sensitive minimal residual disease, or MRD technology, which can detect circulating tumor DNA in the blood of patients with cancer. Circulating tumor DNA on cancer cells is often found in the bloodstream of patients with cancer. As you may know, most DNA resides inside the cell's nucleus, but as a tumor grows, cells die and they're often replaced by new ones, and those dead cells get broken down. Their contents spill into the blood, including DNA, and therefore we can measure the DNA in their bloodstream. Haystack's technology will be used in a longitudinal assessment to help identify cancer recurrence or progression before clinical, biological, or even radiographic evidence indicates.
Why are you doing this?
We have a large Phase 2b 158 patient ASCEND trial evaluating certepetide in metastatic pancreatic ductal cancer coming out in the fourth quarter of this year. That trial has two cohorts. Cohort-A evaluates one dose of 3.2mg/kg certepetide in combination with standard of care. Cohort-B evaluates two doses of certepetide separated by four hours. And so we'll be able to understand whether a second dose of certepetide increases the potential penetration of anti-cancer medications, which also will lead to better outcomes.
But why we're doing this? To further assess the dose and dose regimen of certepetide. We've designed a trial called Fortified. The trial is evaluating a different patient population, specifically patients with metastatic pancreatic cancer who have progressed on their first-line treatment of FOLFIRINOX. The trial has three cohorts, all of whom will receive standard of care gemcitabine and nab-paclitaxel. The first cohort will get an IV push of certepetide, followed by a four-hour continuous infusion of certepetide. The second cohort will only get the IV push of certepetide, followed by placebo infusion. And the third cohort will get standard of care alone chemotherapy.
The goal of this trial really is to assess whether a single IV push of certepetide, followed by a four-hour continuous infusion in combination with standard of care, is more effective than a single IV push. The study will provide us more insight into the pharmacodynamic effect of certepetide specifically, just further bathing that hostile tumor microenvironment with certepetide to enhance the active transport pathway, resulting in more intra-tumoral chemotherapy and better outcomes. I think using the Haystack MRD technology in this trial will enable us to get an early interim read as to whether the continuous infusion arm is more effective than the single IV push by longitudinally evaluating the drop in CTA and other serum biomarkers.
Quotes have been edited for clarity and style