On May 12, 2025 Lantern Pharma Inc. (Nasdaq: LTRN), an artificial intelligence company developing targeted and transformative cancer therapies using its proprietary AI platform, RADR, reported that the U.S. Food and Drug Administration (FDA) has cleared the amendment to its Investigational New Drug (IND) application to initiate a Phase 1b/2 clinical trial of LP-184 in a genomically defined patient population of non-small cell lung cancer (NSCLC) where there is a need to improve patient outcomes (Press release, Lantern Pharma, MAY 12, 2025, View Source [SID1234652890]).
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"This study represents a potential therapeutic opportunity to improve outcomes for patients diagnosed with advanced non-small cell lung cancer with KEAP1, and STK11 alterations independent of KRAS status. Historically, these co-alterations may lead to worse outcomes for patients, due to resistance to treatments such as single agent immunotherapy, chemotherapy, or chemoimmunotherapy. Research to date suggests that dual immunotherapy is the best approach for this disease type, but many patients still progress on treatment, highlighting an area of unmet need that we can potentially improve on by the addition of LP-184 to this combination," said Misty Dawn Shields, M.D. Ph.D. — Division of Hematology/Oncology, Thoracic Oncology, Indiana University: Melvin & Bren Simon Comprehensive Cancer Center, and Lead Investigator for the planned Study.
Strategic Trial Design to Address Critical Treatment Gap in Advanced NSCLC
The biomarker focused Phase 1b/2 clinical trial is designed to target high-risk NSCLC subtypes by evaluating LP-184 in combination with the immune checkpoint inhibitors nivolumab and ipilimumab in patients with advanced NSCLC harboring KEAP1 and/or STK11 mutations and low PD-L1 expression—a population with limited response to existing first-line therapies. The study is designed to assess safety, preliminary efficacy, and biomarker correlations, potentially paving a path toward accelerated development in this genetically defined patient segment that is treatment resistant to many existing approved chemo and immunotherapies.1 Lantern Pharma expects to prepare an application for a Fast Track or Accelerated Approval Designation for this patient population based on data from the planned trial and ongoing analysis from existing models.
This unique trial is aimed at addressing a critical unmet clinical need in lung cancer care: the median overall survival in newly diagnosed, advanced NSCLC patients with KEAP1 and/or STK11 mutations treated with chemo-immunotherapy averages 15 months, substantially lower than outcomes in mutation negative populations. For patients that fail earlier lines of therapies the overall survival tends to skew even lower at approximately 6.3 months.2 This represents a market opportunity exceeding $2 billion annually, given the prevalence and poor prognosis for patients with these mutations.
Mechanistic Rationale for LP-184 in NSCLC
LP-184 is a next-generation, synthetically lethal small molecule that induces DNA double-strand breaks upon activation by prostaglandin-reductase 1 (PTGR1). This enzyme is notably overexpressed in KEAP1-mutant tumors. Preclinical studies demonstrate that LP-184’s cancer-killing potency directly correlates with PTGR1 expression levels in NSCLC cell lines. The company’s proprietary RADR platform-driven in silico analyses and preclinical studies suggest that LP-184 is particularly effective in DNA damage repair (DDR)-deficient cancers, including NSCLC with KEAP1 and STK11 alterations3. An additional advantage of LP-184 is its selective toxicity mechanism: PTGR1 enzymatically converts LP-184 from a prodrug to its bioactive, cytotoxic form specifically within tumor cells where PTGR1 is elevated, while normal tissues with low PTGR1 expression remain largely unaffected. This selective toxicity has been observed pre-clinically and in Lantern’s AI modeling. This tumor-selective activation creates a significant therapeutic window that may enable robust anti-tumor activity while minimizing systemic toxicities.
Another key competitive advantage of LP-184 is its mechanism, which in preclinical models has been demonstrated to remain effective regardless of TP53 status—a common co-mutation that contributes to resistance against current therapies2. Individual or co-occurring KEAP1, STK11, and TP53 mutations are found in approximately 20-30% of NSCLC patients and define molecular subsets unresponsive to standard immune checkpoint blockade4.
Targeting The Right Patients – Combining Potential Clinical Benefit & Likelihood of Response to LP-184 in a Combination Regimen
Clinical data analysis conducted by Lantern Pharma in 517 lung cancer patients from a major cancer database (TCGA) revealed a clear target population for LP-184. About 35% of these patients had high levels of PTGR1 – the enzyme that has been hypothesized to activate LP-184 inside the cancer cell. (Figure 1)
Among these PTGR1-high lung cancer patients, 40% also had KEAP1 mutations, which are linked to poor responses to current immunotherapies and chemotherapies. KEAP1 mutations actually cause higher PTGR1 expression, essentially making these difficult-to-treat tumors more vulnerable to LP-184 based on preclinical observations.
"This clinical trial and the FDA clearance represents a pivotal milestone in our mission to develop precise, data-driven cancer therapies for patients with limited treatment options," said Panna Sharma, President and CEO of Lantern Pharma. "The STK11 and KEAP1 mutant NSCLC population represents an important market opportunity and, a group of patients desperately awaiting better treatment options. By combining our AI-driven approach with a deep understanding of cancer biology, we’ve identified LP-184 as a potential breakthrough for these patients. The clearance of this trial advances our precision oncology strategy while demonstrating the power of our RADR platform to accelerate development timelines and reduce costs, as part of our mission to create value for both patients and shareholders as we work to transform oncology drug development."