Building a Path to Cure for Patients With NSCLC Who Have Never Smoked

On average, there are 577 never-smokers, or people who have smoked 100 or fewer cigarettes in their lifetimes, in the United States who will be diagnosed with non-small cell lung cancer (NSCLC) every week this year.¹ By the end of the year, up to 30,000 never-smokers will have received a diagnosis of NSCLC.¹ While the 5-year survival rate for NSCLC is up to 65% (if the disease is found while localized), there are currently no reliable approved treatments for patients whose cancer has spread or returned, and they quickly run out of options.¹ For the 70% of patients whose cancer has spread to lymph nodes, the 5-year survival rate decreases to 37%, and for those patients whose cancer metastasizes further, the survival rate decreases to 9%.¹

That survival rate is unacceptable in a disease that is difficult for never-smokers to avoid and that typically has no visible symptoms until it is already in an advanced stage. Overall, only 16% of patients with lung cancer receive an early diagnosis, sharply increasing the need for treatment options above and beyond the standard of care in chemotherapy.²

To address this need, investigators have enrolled patients in the multi-center, open-label phase 2 Harmonic clinical trial, which is a multi-center study evaluating the investigational drug LP-300 (Lantern Pharma). This trial is for patients who are never-smokers with relapsed and inoperable advanced primary adenocarcinoma of the lung, which is a type of NSCLC.

NSCLC Cure Rate in Never-Smokers

Up to 80% of cases of lung cancer in never-smokers (LCINS) are adenocarcinoma, which begins in the alveoli, or millions of tiny air sacs in the lungs. When adenocarcinoma is discovered in a late stage, which is often the case for this patient population, it can limit the available treatment options.³ Even for those patients whose NSCLC is discovered in early stages, when surgery is a viable option, it is estimated that between 30% and 55% of patients will experience an incurable recurrence of the disease, which is where the LP-300 drug-candidate is aimed at creating a benefit for these patients.⁴

Up to 80% of cases of lung cancer in never-smokers (LCINS) are adenocarcinoma, which begins in the alveoli, or millions of tiny air sacs in the lungs. Image Credit: © LASZLO - stock.adobe.com

How patients acquire NSCLC also plays a role in health outcomes. While cigarette smoking is linked to approximately 85% of lung cancer cases in the United States, estimates link secondhand smoke to between 18% and 36% of cases of LCINS, while radon exposure is implicated in 7% to 14% of cases.^5,6 Exposure to air pollution, asbestos, diesel exhaust, and other chemicals, along with a family history of lung cancer, can also increase the risk of LCINS. Further, patients may not know they’ve been exposed to these carcinogens—particularly true of radon—and since the CDC does not recommend lung cancer screening for never-smokers, by the time these patients have visible symptoms, the disease has already progressed to an advanced stage. Lung cancer essentially blindsides them.

Research on LP-300 for LCINS

In 2013, researchers completed a series of phase 3 clinical trials to evaluate an LP-300 for its potential to reduce or prevent the adverse effects of chemotherapy in cancer patients with NSCLC. While the results of those clinical trials didn’t support the use of the therapeutic for this purpose in all patients with lung cancer, the data revealed it had the potential to increase positive patient outcomes in never-smokers with NSCLC. In fact, never-smokers in those clinical trials who received LP-300 in combination with chemotherapy showed an increased overall survival rate of 91% and an increased 2-year survival rate of 125%.⁷ Importantly, this data paved the way for future studies into the efficacy of LP-300 in treating LCINS.

What’s Next for NSCLC Research?

In July 2022, the FDA greenlit the launch of the phase 2 Harmonic clinical trial, which is investigating LP-300 for never-smokers with NSCLC. These patients are a unique and growing population whose lung cancer is proven to be genetically different from the same disease found in smokers. The trial, which provided its first treatment in March 2023, is evaluating LP-300’s efficacy when provided in combination with standard of care chemotherapy, pemetrexed and carboplatin. The ongoing phase 2 clinical trial for LP-300 is designed for 90 patients and provides a 2-in-3 chance of receiving LP-300 in addition to standard of care chemotherapy.

The goal is ultimately to find a cure for advanced NSCLC in never-smokers, and this new clinical trial provides hope for accomplishing that for this patient population.

About the Author

Panna Sharma is the president and CEO of Lantern Pharma.

References

1. Cancer.net. Lung cancer— Non-small cell: Statistics. 2023. Accessed November 2, 2023. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/statistics
2. Babar L, Modi P, Anjum F. Lung cancer screening. StatPearls. January 2023. Accessed November 2, 2023. https://www.ncbi.nlm.nih.gov/books/NBK537283/
3. Centers for Disease Control and Prevention. Lung cancer among people who never smoked. Accessed November 2, 2023. https://www.cdc.gov/cancer/lung/nonsmokers/index.htm
4. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Translational Lung Cancer Research. 2014;3(4). doi:10.3978/j.issn.2218-6751.2013.12.05
5. CDC. Lung cancer: What are the risk factors? Accessed November 2, 2023. https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm
6. CDC. Lung cancer among people who never smoked. Accessed November 2, 2023. https://www.cdc.gov/cancer/lung/nonsmokers/index.htm
7. Lantern Pharma receives FDA authorization to initiate its phase 2 clinical trial, Harmonic™, for LP-300 in never smokers with non-small cell lung cancer. [Press Release] Lantern Pharma. July 2022. Accessed November 2, 2023. https://ir.lanternpharma.com/news-events/press-releases/detail/90/lantern-pharma-receives-fda-authorization-to-initiate-its