This phase I/II trial evaluates the safety and effectiveness of an anaplastic lymphoma kinase (ALK) peptide vaccine for treating patients with anaplastic lymphoma kinase rearrangement positive (ALK+) non-small cell lung cancer (NSCLC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). The ALK peptide vaccine is made up of small pieces (peptides) of abnormal (mutated) ALK protein. The instructions to make the ALK protein are kept on the ALK gene. If the ALK gene fuses abnormally with another gene, it causes tumor cells to grow and spread in the body. While this protein can be targeted with anti-cancer medications, further mutations in the protein can cause the cancer to become resistant to these medications. The vaccine is used to teach an individual’s immune system to recognize these abnormal mutations that can cause treatment resistance and mount an immune response. This immune response may prevent tumor cells with an ALK mutation from becoming resistant to treatment.
Additional locations may be listed on ClinicalTrials.gov for NCT05950139.
Locations matching your search criteria
United States
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer CenterStatus: Active
Contact: Vincent K. Lam
Phone: 410-955-8964
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of administering a prophylactic vaccine targeting common ALK resistance mutations in patients with advanced ALK+ NSCLC.
II. To characterize the neoepitope-specific immune response in patients who have been administered the prophylactic neopeptide vaccine.
SECONDARY OBJECTIVES:
I. To evaluate the pattern of acquired resistance mutations at the time of disease progression in vaccinated patients.
EXPLORATORY OBJECTIVES:
I. To assess overall survival (OS) in vaccinated patients.
II. To assess vaccine-related changes in peripheral CD8+ and CD4+ markers of activation, memory, and exhaustion.
III. To assess vaccine-related T-cell receptor (TCR) repertoire changes in the tumor and peripheral blood.
IV. To explore the effects of vaccine therapy on immune cell subsets (e.g., tumor infiltrating lymphocytes, myeloid-derived suppressor cells [MDSCs], regulatory T cells [Tregs]), immune suppressive pathways, activation pathways, cytokines/chemokines or their receptors, and major histocompatibility complex (MHC) expression.
OUTLINE:
PRIMING PHASE: Patients receive the ALK peptide vaccine with polyinosinic-polycytidylic acid (poly-ICLC) subcutaneously (SC) once daily (QD) on days 1, 4, 8, 15, and 22 of cycle 1.
BOOST PHASE: Patients then receive the ALK peptide vaccine with poly-ICLC SC on day 1 of cycle 4 (week 12) and day 1 of cycle 6 (week 20). Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood collection, urine collection, computed tomography (CT) and magnetic resonance imaging (MRI), and biopsy throughout the study.
After completion of study treatment, patients are followed up at 28 days and then every 12-16 weeks for up to 3 years.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorVincent K. Lam