Summary

This phase II/III Lung-MAP trial compares the effect of combination immunotherapy with N-803 (ALT-803) and pembrolizumab versus usual treatment (docetaxel, gemcitabine, pemetrexed, or ramucirumab combined with docetaxel) in patients with non-small cell lung cancer (NSCLC) previously treated with anti-PD-1 or anti-PD-L1 immunotherapy and whose tumor has spread to other places in the body (advanced). N-803 (ALT-803) binds to and activates certain immune cells (natural killer cells and specific T cells). By doing this N-803 may increase tumor cell killing and decrease tumor growth. Chemotherapy drugs, such as docetaxel, gemcitabine, pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study will help to understand whether combination immunotherapy with N-803 and pembrolizumab is better, the same, or worse than the usual approach in treating patients with recurrent NSCLC who previously received anti-PD-1 or anti-PD-L1 immunotherapy.

Objectives

PRIMARY OBJECTIVES:
I. To compare overall survival (OS) between participants randomized to nogapendekin alfa (N-803 [ALT-803]) + pembrolizumab versus standard of care therapy. (Primary Resistance Cohort)
II. To compare overall survival (OS) between participants randomized to N-803 (ALT-803) + pembrolizumab versus standard of care therapy. (Acquired Resistance Cohort)

SECONDARY OBJECTIVES:
I. To compare investigator assessed progression-free survival (IA-PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between the treatment arms.
II. To compare the response rates between the arms.
III. To evaluate duration of response (DoR) among responders.
IV. To evaluate the frequency and severity of toxicities within each treatment arm.

TRANSLATIONAL MEDICINE OBJECTIVE:
I. To establish a blood repository to pursue future studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients may receive standard of care consisting of docetaxel intravenously (IV) over 30-60 minutes on day 1 of each cycle; gemcitabine IV over 30 minutes on days 1 and 8 of each cycle; pemetrexed IV over 10 minutes on day 1 of each cycle; or ramucirumab IV over 30-60 minutes and docetaxel IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout trial.

ARM B: Patients receive pembrolizumab IV over 30 minutes and nogapendekin alfa subcutaneously (SC) on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients then receive nogapendekin alfa SC on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI and collection of blood samples throughout trial.

After sub-study randomization, patients are followed up for 3 years or until death.