Panbela Therapeutics, Inc. has announced the enrollment of the first patient in a Phase I dose escalation study of CPP-1X-S (eflornithine sachets) in patients with STK11 mutant non-small cell lung cancer (NSCLC). The trial, being conducted at Moffitt Cancer Center, will evaluate the safety, toxicity, and recommended Phase II dose of CPP-1X-S in combination with the immune checkpoint inhibitor Keytruda (pembrolizumab). This study marks a crucial step in addressing the unmet needs of patients with this specific NSCLC subtype.
Trial Design and Objectives
The Phase I/II trial, titled "Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC," is designed to first establish the safety and tolerability of CPP-1X-S in combination with Keytruda. The Phase I portion is a dose escalation study. Following the Phase I portion, a Phase II trial will assess the efficacy of the combination. The trial is enrolling patients at Moffitt Cancer Center. More information can be found at https://clinicaltrials.gov/study/NCT06219174?term=DFMO&rank=4.
Rationale for the Combination
STK11 mutations are associated with reduced levels of anti-tumor T cells and immune evasion, leading to poor responses to standard immunotherapy. Jhanelle Gray, M.D., Principal Investigator of the clinical trial, explained, "Options for combining new agents with standard of care immunotherapy is critical to overcoming the reduced levels of anti-tumor T cells and immune evasion that is observed in STK11 mutant tumors. By working with Panbela, we are using CPP-1X-S to modulate polyamine levels and potentially restimulate the immune system, which may be a valuable therapeutic strategy to target these hard-to-treat tumors."
Panbela's Perspective
Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela, highlighted the potential of polyamine modulation in restimulating the immune system. "Preclinical studies have shown that polyamine modulation has the potential to restimulate the immune system. This trial allows us to explore the potential of CPP-1X-S clinically in the STK11 mutant NSCLC population which historically have a poor response to checkpoint inhibitor therapy. Once the safety of CPP-1X-S in combination with Keytruda is established in this Phase I trial, the planned Phase II trial will determine the potential efficacy of combining polyamine targeted therapies with checkpoint inhibitors hopefully demonstrating the first clinical proof of concept of this unique approach."
About CPP-1X-S (Eflornithine)
CPP-1X (eflornithine) is being developed as a single agent tablet or high dose powder sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity. CPP-1X-S is a formulation of eflornithine in a sachet for oral administration.
