First Patient Enrolled in Phase I STK11 Mutant Lung Cancer Trial at Moffitt

Panbela Therapeutics, Inc. (OTCQB: PBLA), based in Minneapolis, announced the enrollment of the first patient in its Phase I dose-escalation study aimed at evaluating CPP-1X-S (eflornithine sachets) in patients with STK11 mutant non-small cell lung cancer (NSCLC). This clinical-stage company focuses on developing groundbreaking treatments for critical unmet medical needs.

The primary objective of the Phase I trial is to identify the maximum tolerated dose of eflornithine in combination with the immune checkpoint inhibitor, Keytruda. The study will also assess the efficacy of this combination, with plans to advance to a Phase II efficacy trial. Initial data from the Phase I trial is anticipated by mid-2025, with the Phase II trial expected to commence in 2024.

Titled “Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC,” the trial is structured into two phases. Phase I is a dose-escalation study to determine the safety, toxicity, and recommended Phase II dose of CPP-1X-S combined with Keytruda. The study will be conducted at an academic medical center in the United States. Detailed trial information is available on clinicaltrials.gov.

Jhanelle Gray, M.D., Principal Investigator of the clinical trial, Chair of Moffitt’s Department of Thoracic Oncology, and Co-Leader of Moffitt’s Molecular Medicine Program, emphasized the importance of combining new treatments with standard immunotherapy to combat immune evasion in STK11 mutant tumors. Dr. Gray noted that working with Panbela to modulate polyamine levels using CPP-1X-S could potentially restimulate the immune system, offering a promising therapeutic strategy for these challenging tumors.

Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela, expressed enthusiasm about the trial, following the recent approval of CPP-1X (DFMO) for neuroblastoma, marking the first oncology approval for a polyamine-targeted therapy. Dr. Simpson highlighted that preclinical studies indicate polyamine modulation could restimulate the immune system. This trial will explore CPP-1X-S's clinical potential in the STK11 mutant NSCLC population, which typically shows poor response to checkpoint inhibitor therapy. Establishing the safety of CPP-1X-S with Keytruda in Phase I will pave the way for Phase II to determine the efficacy of combining polyamine-targeted therapies with checkpoint inhibitors, potentially offering a novel approach for treating these tumors. Additionally, Panbela aims to assess the role of eflornithine and ivospemin in modulating the immune system alongside other therapies like CAR-T for tumors with low immunotherapy response rates.

Panbela's development pipeline includes assets in clinical trials targeting familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention, and ovarian cancer. Their programs range from pre-clinical to registration studies, indicating a steady progression of anticipated developments.

Ivospemin (SBP-101), a proprietary polyamine analogue, is designed to inhibit polyamine metabolism, showing promising tumor growth inhibition in metastatic pancreatic cancer clinical studies. It has demonstrated a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, surpassing the standard gemcitabine and nab-paclitaxel treatment. Importantly, ivospemin has not exacerbated chemotherapy-related adverse events like bone marrow suppression and peripheral neuropathy.

Flynpovi™ combines CPP-1X (eflornithine) and sulindac, using a dual mechanism to inhibit polyamine synthesis and increase polyamine export and catabolism. In a Phase III trial, it prevented over 90% of subsequent pre-cancerous sporadic adenomas versus placebo in patients with sporadic large bowel polyps. For FAP patients with lower gastrointestinal anatomy, Flynpovi significantly delayed surgical events compared to single agents.

CPP-1X, in development as a single agent tablet or high-dose powder sachet, targets several indications, including gastric cancer prevention, neuroblastoma treatment, and recent onset type 1 diabetes. Preliminary studies and early-phase trials suggest CPP-1X is well-tolerated and potentially effective. Panbela Therapeutics, Inc. continues to focus on developing innovative treatments for patients with pressing medical needs, with Ivospemin and Flynpovi as their lead assets.