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M.L. Johnson
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-036 - Appropriate Use of Immune Checkpoint Inhibitors in Advanced NSCLC: Effectiveness of Unique Case-Based Education on Clinical Decision-Making (ID 9441)
09:30 - 09:30 | Author(s): M.L. Johnson
- Abstract
Background:
The past several years have witnessed unparalleled changes in treatment for patients with advanced NSCLC. Although these changes present significant hope, it remains unclear if oncologists have been able to stay current on the breadth of practice changes, and effectively incorporate evidence-base into practice. The objective of this study was to evaluate oncologists’ competence regarding the use of immune checkpoint inhibitors (ICI) in the management of advanced NSCLC and the impact of education on narrowing gaps in clinical practices.
Method:
An online education environment that employed video vignettes to simulate practice, presented 3 CME-certified case activities, each illustrating a clinical challenge. Questions regarding point-of-care decisions were posed as a means of testing the oncologist’s ability to make treatment decisions and to communicate effectively with patients who have NSCLC. These case activities included patients with non-squamous and squamous NSCLC and who exhibited adverse events. For each activity, an assessment instrument using case-based, multiple-choice questions was administered to compare each oncologist’a responses to questions posed before and after the education was presented. Confidentiality of respondents was maintained, responses were de-identified, and aggregated prior to analyses. McNemar's χ[2] test compared learners' responses from pre- to post-assessment. The activities were launched between October 21, 2016, and December 6, 2016, and data were collected through April 26, 2017.
Result:
2,399 oncologists participated in at least one of the 3 activities. Responses of 325 participants who answered all questions during the study period were included. Upon completion of the activities, an improvement was observed in oncologists’ ability to: Identify the correct evidence-based regimen including when to use ICIs for a patient that has progressed on first line therapy (76% vs 98%, P <0.001) Counsel patients on the expected effectiveness of ICI in patients (69% vs 89%, P <0.001) Select the most appropriate monitoring strategy to detect immune-related adverse events in patients receiving an ICI (52% vs 78%, P <0.001) Order appropriate tests to identify the etiology of symptoms that appear during treatment (60% vs 92%, P <0.001) Properly manage immune-related adverse events due to treatment with ICI (67% at baseline to 88% post education, P =0.001) In addition, comfort with prescribing ICIs also increased.
Conclusion:
Use of online, case-based CME utilizing video vignettes to simulate practice improved competence among participating oncologists, demonstrating that online CME can be an effective tool to improve clinical decision-making in the rapidly changing environment of advanced NSCLC disease management.
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P2.07-058 - First-In-Human Study of JNJ-64041757, a Live Attenuated Listeria Monocytogenes Immunotherapy, for Non-Small Cell Lung Cancer (ID 9480)
09:30 - 09:30 | Author(s): M.L. Johnson
- Abstract
Background:
JNJ-64041757 (JNJ-757) is a live attenuated, double-deleted (LADD) Listeria monocytogenes (Lm)-based immunotherapy engineered to induce adaptive immune responses against the tumor-associated antigen mesothelin. The goals of Part 1 of this first-in-human (FIH) study were to establish the recommended phase 2 dose (RP2D), characterize the safety profile, and evaluate the immunological activity of JNJ-757 in patients with adenocarcinoma of the lung.
Method:
This is an ongoing FIH trial in patients with advanced adenocarcinoma non-small cell lung cancer (Stage IIIb or IV) who have progressed after standard therapy (ClinicalTrials.gov: NCT02592967). Patients were treated at 1 of 2 dose levels (10[8] CFU or 10[9] CFU), infused over 1 hour every 3 weeks until disease progression or unacceptable toxicity. Dose limiting toxicities (DLTs) were evaluated during the first cycle. Disease response was assessed every 3 cycles according to RECIST 1.1. Post-infusion blood, urine, fecal, and saliva samples were evaluated for the presence of JNJ-757. Immunological activity of JNJ-757 was assessed by evaluation of peripheral cytokines and immune cells as well as ELISPOT analysis to defined antigens.
Result:
Nine subjects were enrolled; 6 at 10[8] CFU and 3 at 10[9] CFU. There were no DLTs in either dosing cohort, and 10[9] CFU was identified as the RP2D. Most adverse events (AEs) were of grade 1/2 severity, with fatigue, headache, nausea, and vomiting as the most reported events. One drug-related AE of grade ≥3 severity (hypokalemia, grade 3) was reported in the 10[8] CFU cohort. Best response was stable disease. Four patients had received at least 7 cycles (range, 1 to 14 cycles). JNJ-757 was quickly cleared after infusion, with 7/9 patients showing negative blood cultures at 2 hours; all were negative after 24 hours. Correlative studies demonstrated activation of both innate and adaptive immune responses. Natural killer cell and T cell activation were observed 24 hours after infusion, coinciding with elevated cytokine production (i.e., IFN-γ, TNF-α). Specific T cell responses against Listeria listeriolysin O and mesothelin antigens were documented in a subset of patients, consistent with the mechanism of LADD to prime new immune responses.
Conclusion:
The RP2D of JNJ-757 is 10[9] CFU, with a safety profile consistent with other LADD Lm-based agents such as CRS-207. Both innate and mesothelin-specific adaptive immune responses were demonstrated in multiple patients. Recruitment in the trial continues to further characterize the safety profile and immune response, and a phase 1b/2 trial with JNJ-757 and nivolumab is planned.
