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David Noyes
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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
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-35 - Identification and Characterization of a Unique KLRG1-Expressing Subset of CD4+FOXP3+ Tregs in Non-Small Cell Lung Cancer (Now Available) (ID 455)
09:45 - 18:00 | Author(s): David Noyes
- Abstract
Background
It is well established that CD4+FOXP3+ T regulatory cells (Tregs) contribute to dampening anti-tumor responses. Despite our improved understanding of their role in cancer, there remains a knowledge gap with respect to the clonal composition and heterogeneity of tumor-infiltrating Tregs in solid cancers.
Method
We addressed this outstanding issue by conducting comprehensive phenotypic profiling of Tregs present in lung adenocarcinomas of a genetically engineered mouse model of non-small cell lung cancer (NSCLC) as well as those in resected tumors of NSCLC patients.
Result
Multi-parameter flow cytometric analysis revealed that unlike the peripheral tissues, the tumor harbors a distinct sub-population of Tregs that express the co-inhibitory receptor, KLRG1. Compared to their negative counterparts, the KLRG1+ Treg subset exhibited heightened expression of a number of Treg signature proteins as well as higher levels of activation and memory molecular markers suggesting that they are a highly activated and differentiated Treg pool that is recruited to, or induced in the tumor microenvironment. Consistent with this phenotype, these KLRG1+ Tregs were superior in their capacity to suppress T cell proliferation relative to the KLRG1- cells.
Conclusion
Collectively, these findings demonstrate that the tumor microenvironment in non-small cell lung cancer harbors a unique Treg sub-population that is characterized by dominant expression of KLRG1, and which represents a clonal pool with the most potent inhibition of T cell responses. These studies highlight the installment of distinct Treg subsets in NSCLC that have implications for regulation of anti-tumor responses.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-06 - Phase I Study of Nivolumab and Ipilimumab Combined with Nintedanib in Advanced Non-Small Cell Lung Cancer (ID 2000)
10:15 - 18:15 | Author(s): David Noyes
- Abstract
Background
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) inhibit tumor infiltrating lymphocyte activation and are potentially immunosuppressive. Targeting the TME may represent an important synergistic approach in immunotherapy (IO). Combination IO with nivolumab and ipilimumab has proven clinical activity in NSCLC. Nintedanib is an orally available triple kinase inhibitor that is active against NSCLC, inhibits CAFs, and targets VEGFR, FGFR and PDGFR. We report the preliminary results of a phase 1 dose escalation trial evaluating the combination of nintedanib with nivolumab and ipilimumab (N+N+I) in advanced NSCLC pts.
Method
This is single center, investigational, non-randomized trial of IO naïve or IO pretreated pts with locally advanced or metastatic NSCLC. Primary endpoint is to determine the safety and tolerability of concurrent administration of the proposed regimen. Key secondary endpoints include RR, DOR, OS, PFS. Five dose levels of nintedanib (dose level -1, 0, 1, 2 and 3 with nintedanib given at dose 100 mg once daily,150 mg once daily and 100mg, 150 mg and 200 mg twice daily respectively) are given with fixed dose of nivolumab (3mg/kg every 2 weeks) and ipilimumab (1mg/kg every 6 weeks). Dose escalation was achieved by the 3+3 design. Blood and tumor biopsies are obtained to evaluate potential predictive and resistance mechanisms.
Result
Enrollment to phase I dose escalation was started on 29th January 2018 and to date 13 patients have been treated on dose level -1 (3), 0 (5) and 1(5). 54% (7) were IO pretreated and 46% (6) were IO naive. Median age is 65 with 62% (8) female patients, ECOG 1 62% (8) and 15% (2) never smoker/ 85% (11) prior or current smokers. Most common AE of any grade were transaminitis and rash in 23% (3). Most G3 AE was transaminitis 8% (1). There were no G4/5 AEs or DLTs. There was no treatment discontinuation due to AEs. PD-L1 expression was < or = 1% in 46% (6), 1-49% in 8% (1) and >/= 50% in 46% (6) pts. Amongst the 12 patients evaluable for confirmed response, 17% (2) had PR, 50% (6) had SD and 33% (4) had PD. In the IO pretreated group, 14% (1) had PR, 57% (4) had SD and 28% (2) had PD.
Conclusion
The combination of N+N+I was well tolerated. The regimen demonstrates antitumor activity despite progression on prior IO. The updated and mature data of the phase I dose escalation trial will be presented at the meeting. Clinical trial information: NCT03377023.
