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R. Costa
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P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.04-004 - Phase I/Ib Study of Nivolumab and Veliparib in Advanced Solid Tumors and Lymphoma with and without Alterations in Selected DNA Repair Genes (ID 8357)
09:30 - 09:30 | Author(s): R. Costa
- Abstract
Background:
Inhibition of the PD-1/PD-L1 axis with nivolumab has been a successful treatment strategy in a minority of patients with many different tumor histologies (non-small cell lung cancer, squamous cell head and neck cancer, melanoma, Hodgkin lymphoma, renal cell carcinoma, urothelial carcinoma). An increase in the proportion of patients that benefit from this emerging mechanism is needed. Veliparib is an inhibitor of poly (ADP-ribose) polymerase (PARP), and it has been shown in preclinical models and in patients with BRCA mutant ovarian cancer to exert anti-tumor effects through lethal exacerbation of DNA repair defects. Extensive genomic sequencing of tumors of varying histologies has revealed that approximately 5% of all tumors harbor defects in DNA repair genes such as BRCA1/2, RAD51, CHEK1, ATM, ATR, CHEK2, FANCD2, FANCA. We propose combining PD-1 inhibition with nivolumab with PARP inhibition with veliparib in patients with DNA repair gene defects in order to maximize the proportion of patients with clinical responses to these novel treatment strategies.
Method:
We are currently enrolling patients on this phase I/Ib clinical trial at the Northwestern Medicine Developmental Therapeutics Institute. The study schema is shown below. Figure 1
Result:
Section not applicable
Conclusion:
Section not applicable
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P1.04-005 - Phase 2 Study of Nivolumab and Metformin in Advanced Non-Small Cell Lung Cancer with and without Prior Treatment with PD-1/PD-L1 Inhibitors (ID 8505)
09:30 - 09:30 | Author(s): R. Costa
- Abstract
Background:
Inhibition of the PD-1/PD-L1 axis with nivolumab has been proven to be a successful treatment strategy in a minority of patients with non-small cell lung cancer. An increase in the proportion of patients that benefit from this emerging mechanism is needed, and many novel combination therapies are being tested. Furthermore, many patients with non-small cell lung cancer are excluded from further clinical trials if they have received prior checkpoint inhibitor therapy, so this trial provides for this additional unmet need. Epidemiologic studies have consistently demonstrated an association between decreased cancer incidence and mortality in patient treated with metformin. Preclinical models have demonstrated that this anti-cancer effect is potentially mediated by inhibition of insulin like growth factor-1 (IGF-1) and mTOR, as well as activation of AMPK and tuberous sclerosis complex (TSC1, TSC2). Also, metformin has recently been found to exert immunomodulatory functions, inhibiting the exhaustion of CD8+ tumor infiltrating lymphocyte (TIL) function, thereby upregulating tumor-specific immune function. It accomplishes this by preventing apoptosis of CD8+ TILs and converting CD8+ TILs from quiescient central memory T cells to effector memory T cells with active anti-tumor effects. In vivo, the addition of metformin to vaccination enhances the generation of effector memory T cells, congruent with the overall hypothesis. We propose a proof-of-concept parallel phase 2 trial using the combination regimen of nivolumab and metformin. We hypothesize that the combination of nivolumab and metformin will be synergistic and can overcome resistance to single agent PD-1/PD-L1 inhibitors.
Method:
We are currently enrolling patients in this phase II clinical trial at the Northwestern Medicine Developmental Therapeutics Institute. Figure 1
Result:
Section not applicable
Conclusion:
Section not applicable
