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J. Kollmeier
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-003 - A Phase II Study Evaluating the Combination of Everolimus with Carboplatin/Paclitaxel as 1st Line Treatment in Patients with Advanced LCNEC (ID 4370)
14:30 - 14:30 | Author(s): J. Kollmeier
- Abstract
Background:
Approximately 3% of all lung cancers are made up of large cell neuroendocrine carcinoma of the lung (LCNEC). These tumors in general have a bad prognosis and currently there are only very limited treatment options, including platinum derivatives and etoposide. The PI3/AKT/mTOR pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness in different types of NETs, we tested whether everolimus might be also an effective treatment option in advanced LCNEC patients.
Methods:
In this multi-center, open-label, phase II study, everolimus was combined with platin-based chemotherapy in patients with histologically confirmed stage IV LCNEC according to WHO criteria. Further inclusion criteria were measurable disease according to RECIST 1.1 and adequate bone marrow, renal, and liver function. Main exclusion criteria were symptomatic CNS metastases and prior treatment for advanced LCNEC. Enrolled patients received everolimus once a day in combination with 4 cycles of carboplatin and paclitaxel, followed by daily everolimus maintenance therapy. The primary objective was to evaluate the efficacy by assessing the proportion of progression-free patients after three months of treatment.
Results:
Ten German trial sites enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary endpoint (proportion of pts progression-free at month 3) was achieved by 24 patients (49%), assessed by an independent central imaging reviewer. Further efficacy evaluation showed an overall response rate (ORR) until month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median progression-free survival (PFS) of 4.3 months, and a median overall survival (OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled patients with grade 3/4 toxicities in 51%. Most frequent toxicities were diarrhea, fatigue, anemia, and neutropenia.
Conclusion:
The results show that a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor everolimus is an alternative treatment option for LCNEC patients. When comparing to other trials, the effectiveness is comparable to a treatment regimen of cisplatin and etoposide.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-091 - Final Phase Ib Results of RNActive® Cancer Vaccine BI 1361849 and Local Radiation as Maintenance Therapy for Stage IV NSCLC (ID 4735)
14:30 - 14:30 | Author(s): J. Kollmeier
- Abstract
Background:
Preclinical studies demonstrated that local radiotherapy (RT) acts synergistically with RNActive[® ]vaccines to increase tumor-infiltrating immune cells and enhance anti-tumor effects. BI 1361849 (CV9202) is an immunotherapeutic cancer vaccine comprising optimized mRNA constituents (RNActive[®]) encoding six NSCLC-associated antigens. Here we report clinical outcomes and immune response data of a phase Ib study, employing local RT and BI 1361849 in advanced NSCLC.
Methods:
Patients (Pts) with stage IV NSCLC and a response or stable disease after first-line chemotherapy or therapy with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) were enrolled in three cohorts based on histological and molecular NSCLC subtypes (non-squamous vs. squamous vs. EGFR-mutated NSCLC). Pts received two initial vaccinations with BI 1361849 prior to local RT to the primary tumor or a metastatic lesion (four consecutive daily fractions of 5 Gy), followed by further vaccinations until start of another treatment. Maintenance Pemetrexed (mP) and EGFR-TKIs were continued according to the label. Primary endpoint was safety; secondary endpoints included objective response, PFS and OS. Cellular and humoral immune responses were measured ex vivo by multifunctional intracellular cytokine staining, IFN-γ ELISpot, and ELISA in pre- and post-treatment blood samples.
Results:
26 pts were enrolled. 15 pts received mP, two received EGFR TKIs. Most frequent AEs were mild to moderate injection-site reactions and flu-like symptoms. Two pts experienced BI 1361849-related grade 3 AEs (fatigue, pyrexia). No BI 1361849-related SAE or grade 4 AE was reported. Interim results indicate one confirmed PR in a patient receiving mP and SD in 13/25 evaluable pts (52%, 8 pts on mP, 3 pts without maintenance therapy, 2 pts on EGFR-TKI), with two pts showing remarkably long-lasting disease stabilization of up to 72 and 54 weeks, respectively. Shrinkage of lesions outside the irradiated field of ≥15% occurred in 7 pts, all but one receiving mP. Longitudinal assessment of tumor response allows for further insight into patterns of progression. BI 1361849 was capable of eliciting antigen-specific immune responses in the majority of the patients including both cellular and humoral immune responses.
Conclusion:
BI 1361849 elicits antigen-specific immune responses and can be safely combined with local RT and mP treatment. Shrinkage of non-irradiated lesions and prolonged disease stabilization was observed in a subset of pts, mainly in combination with mP. Final clinical outcomes and analyses of cellular and humoral immune responses will be presented.
