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Emily Sisel
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P77 - Immunotherapy (Phase II/III Trials) - Combining Different Immunotherapeutic Approaches (ID 254)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P77.05 - Phase II Study of Imprime PGG and Pembrolizumab in Stage IV NSCLC After Progression on First-Line Therapy: BTCRC-LUN15-017 (ID 1567)
00:00 - 00:00 | Presenting Author(s): Emily Sisel
- Abstract
Introduction
Imprime PGG (Imprime) is a novel β-glucan that acts as a Pathogen Associated Molecular Pattern (PAMP), creating critical “non-self” signals recognized by the innate immune system. Imprime enhances innate immune cell killing, activation of professional antigen presenting cells (i.e. dendritic cells), and T-cell crosstalk, and thereby may enhance the anti-tumor efficacy of checkpoint inhibitors like pembrolizumab. Pembrolizumab is a highly selective, monoclonal IgG4–kappa isotype antibody against PD-1 that can disrupt the engagement of PD-1 with its ligands and impede inhibitory signals in T-cells. Imprime treatment may enhance the efficacy of checkpoint inhibitor therapies like pembrolizumab; however, no studies to date have evaluated the use of Imprime with anti-PD1 therapy in NSCLC.
This trial is a single arm, open-label Phase II study evaluating the combination of pembrolizumab and Imprime in metastatic NSCLC with a primary endpoint of progression-free survival (PFS) after progression on first-line systemic therapy. In Phase Ib, the MTD was determined to be 4 mg/kg. The most common AE was headache in 3 patients. No dose-limiting toxicities or grade 4 AEs were observed. The phase Ib portion of this study found that combination of Imprime and pembrolizumab is well tolerated and the role of this combination in treatment of NSCLC warranted further investigation.1
1. Shergill, A. et al. P1.01-86 BTCRC-LUN15-017: Phase-Ib Study of Imprime PGG and Pembrolizumab in Stage IV NSCLC after Progression on Platinum Based Therapy. Journal of Thoracic Oncology. 2018;13(10), S496.
Methods
The primary objective of Phase II is to estimate PFS benefit measured by RECIST v1.1 in subjects treated with the Phase Ib determined dose of Imprime in combination with pembrolizumab. Key eligibility includes measurable disease, adequate organ function, ECOG performance status of 0-2. Subjects who are candidates for second-line systemic therapy will receive 4 mg/kg Imprime on days 1, 8, and 15 for 4 cycles, and on day 1 for cycles 5-16 (1 cycle=21 days). Pembrolizumab will be administered on day 1 of each cycle after Imprime. Treatment will continue for up to 16 cycles, or until progression or significant toxicity. Patients will be monitored for progression and survival for 5 years (±2 months). Secondary objectives are to characterize AEs, estimate CBR and OS, and correlate clinical benefit with biomarkers on immune cells, soluble PD-1 levels, PD-1 expression on circulating PBMC, anti-β-glucan antibody, and FcγRIIa polymorphism.
The null hypothesis is a median PFS of 3.2 months (equal to single agent pembrolizumab among subjects with a proportion score of 1 to 49%; PFS based on IO-naïve patients and will be updated in results analyses); the alternative hypothesis is PFS of 6.3 months (equal to single agent pembrolizumab among subjects with a proportion score of ≥ 50%). With a sample size of 24 the study will have 90% power to detect a difference of 3.1 months. The Phase II portion has now completed accrual.
