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Muhammad Furqan
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FP03 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) (ID 151)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP03.05 - TLR9 Agonist CMP-001 Plus Atezolizumab +/- Radiation Therapy in Patients With PD-1 Blockade Resistant Advanced NSCLC (ID 3571)
00:00 - 00:00 | Author(s): Muhammad Furqan
- Abstract
- Presentation
Introduction
Patients with non–small cell lung cancer (NSCLC) and progressive disease (PD) following programmed death 1 (PD-1) blockade therapy have a poor prognosis. CMP-001 is a CpG-A Toll-like receptor 9 (TLR9) agonist packaged within a virus-like particle. The multicenter, open-label, 2-part, Phase 1b CMP-001-003 study (NCT03438318) evaluated the safety and preliminary antitumor activity of CMP-001 plus atezolizumab with or without radiation in patients with advanced NSCLC.
Methods
Eligible patients with PD following anti–PD-1/programmed death ligand 1 (PD-L1) therapy and ≥1 extra-central nervous system, non-bone metastasis amenable for intratumoral injection received CMP-001 and atezolizumab (Part A) or CMP-001, atezolizumab, and radiation (Part B). CMP-001 was administered at 5 mg subcutaneously once weekly during weeks 1 and 2, followed by 5 mg or 10 mg intratumorally once weekly during weeks 3-5 and every 3 weeks thereafter. Atezolizumab 1200 mg was administered intravenously once every 3 weeks starting on week 2. Radiation therapy in Part B consisted of 20 Gy delivered in 5 fractions starting ≥2 days prior to CMP-001 treatment. Following a safety run-in period (n=5), each Part enrolled additional patients in Stage 1; ≥2 of 12 patients were required to have a RECIST v1.1 response to proceed with Stage 2 enrollment. The primary objective was to evaluate the safety of CMP-001 and atezolizumab with or without radiation. A key secondary endpoint was best objective response per RECIST v1.1 as assessed by the investigator.
Results
Twenty-nine patients were enrolled in Stage 1 (Part A, n=13; Part B, n=16). The median number of prior lines of therapy received was 3 (range, 1-6); 31.0% of patients had ≥4 prior lines of therapy. Only 5 patients (17.2%) had response to any prior systemic therapy. The median number of CMP-001 intratumoral injections was 3 (Part A range, 1-12; Part B range, 1-6); 12 patients had a total of 65 injections into visceral lesions, including kidney, liver, lung, and pleura, which were safely performed. The most common treatment-related adverse events (TRAEs; ≥30%) overall were flu-like symptoms (ie, chills and pyrexia) and hypotension. Six patients (46.2%) in Part A and 8 patients (50.0%) in Part B had grade ≥3 TRAEs. Only 1 patient discontinued treatment due to TRAEs (Part A, grade 3 pneumonitis). As of April 15, 2020 (Part A median follow-up, 1.9 months [range, 1-19]; Part B median follow-up, 1.7 months [range, 1-4]), no objective responses were observed. Two patients (15.4%) and 4 patients (25.0%) had tumor shrinkage (<30% decrease in tumor size) in Parts A and B, respectively. Three patients (23.1%) and 8 patients (50.0%) had stable disease as best response in Parts A and B, respectively. Study enrollment was stopped after completion of Stage 1 due to lack of objective response. The cytokine response to CMP-001 treatment and tissue biopsy analyses will be presented.
Conclusion
CMP-001 plus atezolizumab with and without radiation therapy had a manageable safety profile. Intratumoral injection of CMP-001 into visceral lesions was safely achieved, and stable disease was observed in heavily pretreated patients with PD-1/PD-L1 refractory NSCLC.
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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 | Author(s): Muhammad Furqan
- 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.
