Abstract 244: Abscopal responses in patients with refractory metastatic NSCLC treated with concurrent radiotherapy and CTLA-4 immune checkpoint blockade: evidence for the in situ vaccination hypothesis of radiotherapy

e20512 Background: Veristrat (Biodesix, Boulder, CO) is a blood based proteomic assay that is dominated by inflammatory proteins and is prognostic and predictive in metastatic NSCLC after treatment with platinum based chemotherapy (Gregorc et al, Lancet 2014). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). There is preclinical evidence to suggest that the tumor microenvironment can be altered with immunomodulatory interventions (Martino et al, 2016). While immune checkpoint blockade has shown durable benefit in metastatic NSCLC, the response rates still hover around 20%. As a result, identification of predictive biomarkers are of critical importance. The predictive value of the Veristrat assay with respect to ICB is poorly defined. Methods: At our institution, 83 pts with metastatic lung cancer pts were treated with nivolumab between 6/2015 to 12/2016. The following clinicopathologic characteristics were abstracted from medical records: tumor histology, Veristrat status, no. of doses of nivolumab, irAEs and overall survival. Results: Of the 83 pts, 65 pts were found to have NSCLC. Veristrat status was available for 17/65 of these pts. Nine pts were identified to have “Veristrat good” and seven pts were “Veristrat poor”. Median number of nivolumab doses was 4. Median survival for all patients was 30 weeks. Median survival was 20 weeks for “Veristrat poor” and 26 weeks for “Veristrat good”(p = 0.68). Grade 3-4 irAEs were noted in 5/9 patients with “Veristrat good” and 5/7 patients with “Veristrat poor”. Conclusions: “Veristrat poor” pts treated with ICB have a lower median survival as compared to “Veristrat good” pts. Our study did not meet statistically significant end point due to limited sample size. Further studies are needed to identify poorly immunogenic tumors and develop novel treatment approaches to optimize outcomes. [Table: see text]

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In situ thermal ablation of tumors in combination with nano-adjuvant and immune checkpoint blockade to inhibit cancer metastasis and recurrence

Biomaterials ◽

10.1016/j.biomaterials.2019.119490 ◽

2019 ◽

Vol 224 ◽

pp. 119490 ◽

Cited By ~ 8

Author(s):

Xiao Han ◽

Rui Wang ◽

Jun Xu ◽

Qian Chen ◽

Chao Liang ◽

...

Keyword(s):

Immune Checkpoint ◽

Thermal Ablation ◽

Cancer Metastasis ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade

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Correction: In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001481corr1 ◽

2021 ◽

Vol 9 (10) ◽

pp. e001481corr1

Keyword(s):

Photodynamic Therapy ◽

Immune Checkpoint ◽

Antitumor Immunity ◽

Rho Kinase ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Kinase Inhibition

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In Situ Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy

Nanomaterials ◽

10.3390/nano11020471 ◽

2021 ◽

Vol 11 (2) ◽

pp. 471

Author(s):

Jihoon Kim ◽

David M. Francis ◽

Susan N. Thomas

Keyword(s):

Cancer Immunotherapy ◽

Immune Checkpoint ◽

Cytotoxic T Lymphocyte ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

High Rate ◽

Immune Checkpoints ◽

Safe Delivery ◽

Therapeutic Class

The therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8+ T cell-mediated anticancer immunity. However, low rates of patient responses and the high rate of immune-related adverse events remain significant challenges to broadening the benefit of this therapeutic class, termed immune checkpoint blockade (ICB). To overcome these significant limitations, controlled delivery and release strategies offer unique advantages relevant to this therapeutic class, which is typically administered systemically (e.g., intravenously), but more recently, has been shown to be highly efficacious using locoregional routes of administration. As such, in this paper, we describe an in situ crosslinked hydrogel for the sustained release of antibodies blocking CTLA-4 and PD-1 signaling from a locoregional injection proximal to the tumor site. This formulation results in efficient and durable anticancer effects with a reduced systemic toxicity compared to the bolus delivery of free antibody using an equivalent injection route. This formulation and strategy thus represent an approach for achieving the efficient and safe delivery of antibodies for ICB cancer immunotherapy.

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Checkpoint Blockade in Lung Cancer With Driver Mutation: Choose the Road Wisely

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_280795 ◽

2020 ◽

pp. 372-384 ◽

Cited By ~ 3

Author(s):

Antonio Calles ◽

Jonathan W. Riess ◽

Julie R. Brahmer

Keyword(s):

Lung Cancer ◽

Patient Outcomes ◽

Targeted Therapies ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Driver Mutation ◽

Smoking History ◽

Metastatic Nsclc ◽

Molecular Aberrations

Immune checkpoint blockade with PD-(L)1 antibodies has revolutionized the treatment of advanced non–small cell lung cancer (NSCLC). Similarly, the identification and targeting of oncogene drivers in metastatic NSCLC has dramatically improved patient outcomes with an expanding list of potentially actionable alterations and targeted therapies. Many of these molecular aberrations are more common in patients with little or no smoking history and adenocarcinoma histology. Certain molecular subsets of NSCLC, though gaining greatly from targeted therapy approaches, may derive less benefit from immune checkpoint blockade. The optimal identification, targeting, and sequencing of targeted therapies, immunotherapy, and chemotherapy are essential to continue to improve patient outcomes in advanced NSCLC. Herein, we review the role of immunotherapy in locally advanced and metastatic disease for patients with actionable driver alterations. Never-smoking patients have a high probability of having lung cancer that harbors one of these molecular aberrations that can be matched to a tyrosine kinase inhibitor with greatly improved clinical outcomes. Some of these patients with driver mutations may derive less benefit from immune checkpoint inhibitor approaches (either alone or combined with chemotherapy), especially compared with smoking-associated NSCLC. Given that PD-1 blockade alone or with platinum-based chemotherapy is the de facto first-line therapy (depending on level of PD-L1 expression) for nontargetable metastatic NSCLC, we also review treatment in never-smoking patients for whom molecular testing results are pending and the likelihood of identifying a driver mutation is high.

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