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Jennifer G. Whisenant



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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-17 - Phase I/II Study of Nivolumab and Vorolanib in Patients with Refractory Thoracic Tumors (ID 2443)

      09:45 - 18:00  |  Author(s): Jennifer G. Whisenant

      • Abstract

      Background

      Single-agent nivolumab has limited efficacy in thoracic tumors. The antitumor activity of VEGF TKIs is typically attributed to their effect on angiogenesis; however, emerging data suggest these agents can modulate the immune system, especially in the immune suppressive microenvironment. Preliminary results in multiple solid tumors demonstrated clinical benefit when nivolumab was added to anti-angiogenic agents albeit with increased toxicities. Vorolanib was designed to improve the safety profile without compromising efficacy. No dose-limiting toxicities (DLTs) from vorolanib were reported in multiple single-agent phase I trials.

      Method

      NCT03583086 is an ongoing multi-institutional, phase I/II study of nivolumab and vorolanib in patients with thoracic tumors who have failed at least one prior line of therapy. A standard 3+3 dose escalation design was planned with three doses of vorolanib (200, 300, and 400 mg once-daily) and 240 mg nivolumab every two weeks to determine the maximum tolerated dose. Phase II will evaluate the response rate in five cohorts: PD-1/PD-L1 naïve non-small cell lung cancer (NSCLC), PD-1/PD-L1 primary refractory (defined as progression on PD-1/PD-L1 therapy within 12 weeks), NSCLC patients with acquired resistance (achieved at least stable disease and then progressed) to PD-1/PD-L1, thymic carcinoma, and small cell lung cancer patients who have progressed on prior platinum-based chemotherapy. Exploratory correlatives will assess changes in the innate and adaptive immune responses after treatment.

      Result

      Phase I enrolled 10 patients (eight NSCLC and two thymic cancers); one patient was not evaluable for DLT and replaced. No DLTs were observed in three patients at the first dose level of 200 mg. Vorolanib was escalated to 300 mg, and elevated ALT (Grade 3) occurred in two of six patients just beyond the DLT period but deemed clinically significant; thus, 200 mg vorolanib with 240 mg nivolumab is being evaluated in expansion cohorts. The most common adverse events were elevated ALT, AST, and lipase, diarrhea, and fatigue; most were Grade 1/2. Grade 4 hyperglycemia and elevated lipase and Grade 3 elevated serum amylase occurred in one patient each. In seven efficacy-evaluable patients (2 immunotherapy naïve NSCLC; 3 NSCLC with prior immunotherapy; 2 thymic cancer), two partial responses were observed (1 PD-1/PD-L1 naive NSCLC and 1 thymic cancer patient); the NSCLC patient was also PD-L1 negative. Three NSCLC patients with prior PD-1/PD-L1 inhibitors had tumor regression; two of these had acquired resistance and the other was primary refractory to prior immunotherapy.

      Conclusion

      The combination of 200 mg vorolanib and 240 mg nivolumab was generally well tolerated. Clinical activity was observed in both PD-1/PD-L1 naïve patients and those treated with prior immunotherapy. Final phase I results and available phase II data will be presented.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-08 - Preliminary External Validation of the Clinical Definitions of Resistance to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer  (ID 2837)

      10:15 - 18:15  |  Author(s): Jennifer G. Whisenant

      • Abstract

      Background

      Immune checkpoint inhibitors (ICIs) have become an important component of treatment for patients with advanced stage non-small cell lung cancer (NSCLC). Unfortunately, the majority of patients on ICIs will eventually progress. Based on the results from a meta-analysis review of the current ICI literature, Gillaspie et al developed a clinical radiographic response criterion to classify patients as having innate, acquired resistance or durable response to ICIs. The objective of this study was to validate this categorization using prospectively collected clinical data.

      Method

      The study population consisted of Stage IIIB and IV, biopsy-proven NSCLC patients from a single institution treated on or off a clinical trial with single agent ICIs in the first, second line or beyond. De-identified tumor data, stage and treatment data long with response to ICIs were collected prospectively into a database. Patients were censored at last date of follow-up if no progression had occurred. Progression-Free survival (PFS) curves and rates were estimated using the Kaplan-Meier method and then compared to the categorization established by the meta-analysis.

      Result

      From April 2012 to January 2018, 231 patients met criteria for inclusion and analysis. Median age was 65 years, 61% were male and 92% white. Forty-three (18.6%) received ICI in the first line, while the remaining 188 were treated in the second line or above. Analogous to the meta-analysis, our single center data demonstrated three distinct sub-populations of response. PFS curve slopes were evaluated and compared between the proposed classification and our single center experience (Table 1). The slopes of the curves are similar for the Innate, Adaptive or Acquired Resistance and Durable Response categories established in the meta-analysis. Our single-center experience resulted in a slightly steeper slope in the innate response category compared to the clinical trial literature. This may be explained by our cohort including patients who are treated in the third line or beyond whereas most of the meta-analysis trials restricted populations to either first or second line only. A steeper PFS curve would be expected in a more heavily treated population.

      Table 1
      PFS Slope Meta-Analysis PFS Slope Validation
      Innate Resistance 12.9 14.0
      Aquired Resistance 3.8 3.4
      Durable Response 1.2 1.1

      Conclusion

      This single center assessment of the proposed classification for resistance to immune checkpoint inhibitors in non-small cell lung cancer confirms the three distinct subgroups of response based on a comparison of the PFS curves. A formal statistical validation will be performed and presented. Future studies are planned to include prospectively collected data from additional comprehensive cancer centers within the validation cohort.