Summary
Background A single center phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab (GNP) to evaluate the safety and efficacy in metastatic pancreatic adenocarcinoma (PDAC) was conducted (NCT02331251). Methods PDAC patients (pts) with measurable disease, biopsy proven metastasis, adequate laboratory tests, and KPS ≥ 70% received GNP until progression or toxicity. Safety monitoring, RECIST 1.1, and irRECIST assessments were conducted. Response imaging was performed prior to cycle 4, then every 3 months. Changes in tumor cell-free DNA copy number instability (CNI) was retrospectively evaluated. Results 17 pts. with a median age of 56 were treated. 11 were women and all had a KPS of at least 80%. Grade 3 events occurred in 53% of patients. The phase II portion was completed for chemotherapy naïve PDAC pts. Of the 11 evaluable chemotherapy naïve PDAC, the disease control rate (partial response [PR] + stable disease[SD]) was 100%. There were 3 with PR on treatment for 8+, ~11, and 15 months; respectively. The primary endpoint of >15% complete response was not met. The median progression-free survival (PFS) and overall survival (OS) was 9.1 and 15.0 months for chemotherapy naïve treated patients. Of 9 patients evaluable for CNI change, a greater reduction in CNI correlated with longer PFS and improved OS. Conclusions GNP can be safely given to chemotherapy naïve PDAC patients. Efficacy appears to be slightly improved over previously reported results for standard weekly × 3 every 28 day gemcitabine and nab-paclitaxel dosing. CNI change may be prognostic for OS.
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Change history
24 April 2019
The authors would like to note an error in Figures��1 and 2 of this paper. The graph in Figure 1 incorrectly reflected the overall survival (OS), when it should have displayed the progression-free survival (PFS). The caption and median PFS values were correct.
24 April 2019
The authors would like to note an error in Figures��1 and 2 of this paper. The graph in Figure 1 incorrectly reflected the overall survival (OS), when it should have displayed the progression-free survival (PFS). The caption and median PFS values were correct.
Abbreviations
- AEs:
-
Adverse events
- CNI:
-
Tumor cell-free DNA copy number instability
- CI:
-
Confidence interval
- DC:
-
Disease control
- DLT:
-
Dose-limiting toxicity
- irAEs:
-
Immune-related adverse events
- irRECIST:
-
Immune-related response criteria
- GNP:
-
Gemcitabine and nab-paclitaxel
- MTD:
-
Maximum tolerated dose
- NSCLC:
-
Non-small cell lung cancer
- OS:
-
Overall survival
- PD:
-
Disease progression
- PDAC:
-
Pancreatic adenocarcinoma
- PD-1:
-
Programmed cell death protein 1
- PD-L1:
-
PD-1 ligand
- PFS:
-
Progression-free survival
- RP2D:
-
Recommended phase 2 dose
- SD:
-
Stable disease
- TEAE:
-
Treatment-emergent AE
- WIRB:
-
Western Institutional Review Board
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Acknowledgements
The authors express their gratitude and appreciation to all those that participated.
Funding
This study was funded by Western Regional Medical Center, Inc.
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Contributions
Conception and design: G. Weiss, V. Khemka
Acquisition of data: All authors
Analysis and interpretation of data: All authors
Writing, review, and/or revision of the manuscript: All authors
Administrative, technical, or material support (eg, reporting or organizing data, constructing databases): All authors
Study supervision: G. Weiss, V. Khemka
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Conflict of interest
G. Weiss has been a paid consultant for Blend Therapeutics, Pharmatech, IDEA Pharma, AZ Medical Board, GLG Council, Ignyta, Circulogene Theranostics, Viomics, and Paradigm, has received speaker honorarium from Medscape, Merck, Novartis, and Pfizer; holds ownership interest in Circulogene Theranostics, and travel/accommodations from NantWorks, Cambridge Healthtech Institute, and Tesaro. J. Beck, K. Bornemann-Kolatzki, H. Urnovitz, and E. Schütz are employees of and hold ownership interest in Chronix Biomedical. V. Khemka has been a paid consultant for Axcess Oncology. No potential conflicts of interest were disclosed by the other authors.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Weiss, G.J., Blaydorn, L., Beck, J. et al. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs 36, 96–102 (2018). https://doi.org/10.1007/s10637-017-0525-1
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DOI: https://doi.org/10.1007/s10637-017-0525-1