On April 25, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported that the first participants have been enrolled in a study that is part of an 800-site master protocol trial for non-small cell lung cancer (NSCLC) (Press release, ImmunityBio, APR 25, 2022, View Source [SID1234612905]). The Lung Cancer Master Protocol trial (Lung-MAP) includes a study of Anktiva (N-803) plus Keytruda (pembrolizumab) versus investigator choice of standard-of-care chemotherapy in patients with non-small cell lung cancer (NSCLC) whose cancer has progressed after prior checkpoint-inhibitor-containing regimens. The study, which opened in March and currently includes nearly 200 sites across the U.S., will involve 478 patients when fully enrolled.

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"The Lung-MAP master protocol is an important and innovative national multicenter trial and we’re grateful to be working with this national network to validate our hypothesis that both NK and T cells are needed to establish durable responses in patients with lung cancer," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "This large trial will provide valuable information on the role Anktiva could potentially play in bolstering the effectiveness of checkpoint inhibitors such as Keytruda. Since Anktiva acts by activating and proliferating both NK and memory T cells, the combination with a checkpoint inhibitor that takes the brakes off T cells could result in improved durable outcomes. This combination therapy will be offered as a treatment option to patients with tumors that do not have druggable mutations, which is the case for the majority of NSCLC patients."

About the Anktiva (N-803) Lung-MAP Trial

The trial protocol is enrolling patients to a randomization schema of N-803 + pembrolizumab versus investigator choice of standard-of-care chemotherapy (docetaxel, gemcitabine, pemetrexed, or docetaxel + ramucirumab). The two cohorts are being studied independently: 1. Primary checkpoint inhibitor resistant patients, 2. Previous responders to checkpoint inhibitors who then subsequently progress.

The current standard-of-care for NSCLC without targetable mutations is pembrolizumab (Keytruda). This Lung-MAP study will look at how N-803 could potentially bolster the effectiveness of Keytruda for patients with non-targetable cancer cell mutations. The current standard of care for patients who progress on Keytruda is chemotherapy, which has significant toxicities associated with its use. Data presented by Wrangle and colleagues at ASCO (Free ASCO Whitepaper) 2021 showed the N-803/Keytruda combination as a chemotherapy-free alternative that has produced lower rates of adverse events than chemotherapy in the second-line setting View Source

To learn more about the Lung-MAP study, please visit View Source or clinicaltrials.gov (NCT05096663).

"We are incredibly excited to begin a randomized trial of N-803 plus pembrolizumab compared to second line chemotherapy," said John Wrangle, M.D., a researcher at the Medical University of South Carolina who developed the study. "Lung-MAP S1800D will let us study if we can prolong the duration of benefit a patient experiences from immunotherapy while delaying use of cytotoxics. We have already observed that the combination is safe and that it can shrink tumors that have progressed on immunotherapy. Now it’s time for a rigorous trial to determine if that means patients experience prolonged survival in the real-world setting that the Lung-MAP mechanism provides."

Incidence of Lung Cancer

According to the American Cancer Society, lung cancer is the second most common cancer in the U.S. and remains a significant cause of death. It is estimated that nearly 237,000 new cases of lung cancer will be diagnosed in the U.S. this year, leading to some 130,000 deaths attributed to the disease. Non-small cell lung cancer accounts for about 80% to 85% of all lung cancer diagnoses; there are very few successful treatment options for these patients once the cancer spreads beyond the lungs. The development of checkpoint inhibitors in NSCLC has been revolutionary, doubling the median overall survival in some settings; however, patient response may be short lived, due to late response and/or progression after achieving an initial response.

ImmunityBio’s IL-15 superagonist Anktiva (N-803)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. Anktiva is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. Compared to native, non-complexed IL-15 in vivo, Anktiva has better pharmacokinetic properties, due to longer persistence in lymphoid tissues, and enhanced anti-tumor activity.

Anktiva is currently being studied in 21 clinical trials across 14 indications.

About Lung-MAP

Launched in 2014, Lung-MAP, or the Lung Cancer Master Protocol, is a precision medicine clinical trial for people with advanced non-small cell lung cancer that has continued to grow after treatment. As the largest "umbrella" lung cancer trial in the U.S., Lung-MAP is simultaneously studying how well multiple investigational or new drugs work in NSCLC with specific gene mutations or biomarkers. Open at almost 800 sites across the U.S., Lung-MAP is a unique public-private collaboration among the National Cancer Institute (NCI), which is part of the National Institutes of Health, SWOG Cancer Research Network, Friends of Cancer Research, the Foundation for the National Institutes of Health (FNIH), and 13 pharmaceutical companies.