Immunogenicity and Safety of the Prame Cancer Immunotherapeutic in Non-Small Cell Lung Cancer (NSCLC): Phase I Dose Escalation Study

ABSTRACT Introduction Adjuvant chemotherapy (CT) is the standard treatment for stage II–IIIA NSCLC, but is debated for stage IB. As not all patients (pts) are eligible for CT and many of them relapse, alternative therapies are needed. The PRAME tumor antigen, expressed frequently in NSCLC and at lower levels in few normal cells, offers an attractive target for active immunization. Moreover, while most NSCLC tumors expressing the antigen MAGE-A3 are PRAME positive, 45% of PRAME-expressing NSCLC do not express MAGE-A3. This dose-escalation phase I open study aimed at determining the optimal dose of the PRAME cancer immunotherapeutic (PRAME recombinant protein (recPRAME) with AS15 immunostimulant) by evaluating its safety and immunogenicity in NSCLC pts. Methods Pts with PRAME-positive resected stage IB-IIIA NSCLC were enrolled in 3 consecutive cohorts to receive up to 13 injections of recPRAME (20 µg, 100 µg, and 500 µg) with AS15 (fixed dose) over approximately 2 years. Adverse events (AEs), including pre-defined dose-limiting toxicity (DLT), were recorded throughout the study. The anti-PRAME humoral and cellular responses were assessed post-dose 4 by ELISA and flow cytometry (PRAME-specific T-cells producing both IFNγ and TNFα), respectively. Results 60 pts were treated in the study (18, 18, 24 pts received 20, 100, 500 µg recPRAME, respectively). AEs were mostly grade 1/2. No grade 3/4 AEs considered by the investigator to be causally related were reported. One grade 2 serious AE causally related to PRAME administration was reported. No DLTs were reported. Immunogenicity results are shown in the table. Conclusions The PRAME cancer immunotherapeutic was well-tolerated and elicited similar humoral responses in all 3 cohorts. A trend for an increased cellular response was observed with increasing dose of recPRAME. Thus, the highest dose was selected for further clinical development. Immunogenicity post-dose 4 (ATP population). Cohort (recPRAME dose) 1 (20 µg) 2 (100 µg) 3 (500 µg) Humoral responders, n/N* 10/10 11/11 19/19 CD4+ T-cell responders, n/N* (%) 3/9 (33%) 6/10 (60%) 12/15 (80%) CD8+ T-cell responders, n/N* (%) 0/8 (0%) 0/10 (0%) 0/13 (0%) N, number of patients enrolled into each group; * number of patients with pre and post-vaccination results; n, number of responders; ATP, according-to-protocol Funding GSK Biologicals Disclosure J. Pujol: Honorarium study coordination as only conflict of interest. B. Kubisa: I am the Principal Investigator of this study at my institution. E. Vallieres: I am a consultant for GLAXOSMITHKLINE BIOLOGICALS and a member of the PRAME NSCLC Global Development Advisory Board. B. Salaun: Currently employed by GSK Vaccines as a scientist. N. Vanhoutte: Employee of GlaxoSmithKline Biologicals. M. Debois: Employee of GlaxoSmithKline Biologicals. V. Brichard: GSK employee. All other authors have declared no conflicts of interest.