Immune checkpoint inhibitors have minimal activity in unselected CRPC patients (pts). Combination regimens that generate a tumor-directed immune response (vaccine) and facilitate the resulting anti-tumor immune activity (checkpoint blockade, cytokines) have shown synergy in preclinical models. BNVax is a therapeutic poxviral vaccine targeting brachyury, a transcription factor involved in invasion and metastasis. BA is a bifunctional fusion protein: anti-PD-L1 monoclonal antibody fused to the TGF-β-RII receptor extracellular domain (a TGF-β trap). N-803 is an IL-15 superagonist complex. Here we report an interim efficacy analysis of the QuEST1 study, aimed to rapidly interrogate safety and efficacy of immunotherapy combinations in CRPC.
Asymptomatic/minimally symptomatic CRPC pts received BNVax + BA (Arm 2.1) or BNVax + BA + N-803 (Arm 2.2). BNVax is given as 2 prime doses followed by boosts. BA 1,200 mg intravenously and N-803 15 μg/kg subcutaneously are given every 2 weeks. Efficacy is defined as objective response by RECIST v1.1 or PSA decrease ≥ 30% sustained for ≥ 21 days. Safety was a secondary endpoint.
As of 4/26/20, 22 CRPC pts enrolled and had 3 to 17 months follow up. 1/13 pts (Arm 2.1) had a PSA response sustained for 13 months. 4/9 (44%) pts (Arm 2.2) had sustained PSA responses; 2 of these pts had confirmed PR, including 1 pt who progressed on abiraterone and enzalutamide. There were no DLTs or grade >3 treatment-related adverse events (TRAEs). Grade 3 TRAEs: 1 pancreatitis (Arm 2.1), 1 secondary adrenal insufficiency (Arm 2.1), and 1 hyperglycemia due to new onset diabetes mellitus (Arm 2.2). Table: 616MO
|PSA Response/ # Evaluable (%)||# with Measurable Disease by RECIST||BOR in Pts with Measurable Disease by RECIST|
|BNVax + BA||1/13 (7.8%)||3||0||0||1||2|
|BNVax + BA + N-803||4/9 (44%)||3||0||2||1||0|
BVax + BA + N-803 demonstrated a manageable safety profile and preliminary evidence of efficacy in CRPC. Addition of N-803 in Arm 2.2 was associated with more activity in this small sample. Arm 2.2 met the predetermined threshold for efficacy and will expand (n=25).
Clinical trial identification
NCT03493945. First posted April 11, 2018.
Debra Weingarten, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute.
Legal entity responsible for the study
Center for Cancer Research, National Cancer Institute.
The National Cancer Institute, National Institutes of Health has Cooperative Research and Development Agreements (CRADAs) with Bavarian Nordic, Merck KGaA, and ImmunityBio.
All authors have declared no conflicts of interest.