TY - JOUR
T1 - A Phase Ib Study of Single-Agent Idelalisib Followed by Idelalisib in Combination with Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma
AU - Borazanci, Erkut
AU - Pishvaian, Michael J.
AU - Nemunaitis, John
AU - Weekes, Colin
AU - Huang, Julie
AU - Rajakumaraswamy, Nishanthan
N1 - Funding Information:
This study was funded by Gilead Sciences, Inc. The authors would like to thank the individuals and their families for participating in the study. Writing and editorial support were provided by Katelynn Milora, Ph.D., and Nicole Seneca, Ph.D., of AlphaBioCom LLC (King of Prussia, PA).
Funding Information:
This study was funded by Gilead Sciences, Inc. The authors would like to thank the individuals and their families for participating in the study. Writing and editorial support were provided by Katelynn Milora, Ph.D., and Nicole Seneca, Ph.D., of AlphaBioCom LLC (King of Prussia, PA).
Publisher Copyright:
© AlphaMed Press; the data published online to support this summary are the property of the authors.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Lessons Learned: Although this study of idelalisib in patients with PDAC was limited in size and duration because of early termination, idelalisib exposure resulted in an overall safety profile consistent with studies in hematological malignancies, except that the incidences of diarrhea and colitis were reduced in patients with PDAC. Preclinical studies of the PI3K pathway in PDAC and positive clinical results of PI3K inhibition in other cancers support the continued development of PI3K inhibitors in PDAC. Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid tumors and is often refractory to treatment. Phosphatidylinositol-3 kinase (PI3K) δ inhibition influences regulatory immune cell function and improves survival in preclinical PDAC models. Here, idelalisib, an inhibitor of PI3Kδ, was investigated as treatment for metastatic PDAC. Methods: This was an open-label, multicenter, phase Ib, nonrandomized, dose-escalation study. Study aims were to investigate the maximum tolerated dose, safety, pharmacokinetics/pharmacodynamics, and efficacy of idelalisib alone and in combination with chemotherapeutics—nab-paclitaxel and modified (m)FOLFOX6. Results: Because of early termination, only 16 patients were enrolled in the single-agent idelalisib arm, 12 of whom received at least one dose of idelalisib. The most common treatment-emergent adverse events (≥25%) related to idelalisib (n = 12) were increased aspartate aminotransferase, pyrexia, and maculopapular rash. One patient presented with diarrhea; no cases of colitis were reported. One patient discontinued treatment because of pyrexia and maculopapular rash; two patients died because of disease progression. Conclusion: This study was terminated because factors contributing to safety concerns in phase III studies of idelalisib for hematological malignancies were not fully understood. In this small sample of patients with metastatic PDAC, exposure to idelalisib resulted in safety findings consistent with previous studies, with reduced diarrhea/colitis.
AB - Lessons Learned: Although this study of idelalisib in patients with PDAC was limited in size and duration because of early termination, idelalisib exposure resulted in an overall safety profile consistent with studies in hematological malignancies, except that the incidences of diarrhea and colitis were reduced in patients with PDAC. Preclinical studies of the PI3K pathway in PDAC and positive clinical results of PI3K inhibition in other cancers support the continued development of PI3K inhibitors in PDAC. Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid tumors and is often refractory to treatment. Phosphatidylinositol-3 kinase (PI3K) δ inhibition influences regulatory immune cell function and improves survival in preclinical PDAC models. Here, idelalisib, an inhibitor of PI3Kδ, was investigated as treatment for metastatic PDAC. Methods: This was an open-label, multicenter, phase Ib, nonrandomized, dose-escalation study. Study aims were to investigate the maximum tolerated dose, safety, pharmacokinetics/pharmacodynamics, and efficacy of idelalisib alone and in combination with chemotherapeutics—nab-paclitaxel and modified (m)FOLFOX6. Results: Because of early termination, only 16 patients were enrolled in the single-agent idelalisib arm, 12 of whom received at least one dose of idelalisib. The most common treatment-emergent adverse events (≥25%) related to idelalisib (n = 12) were increased aspartate aminotransferase, pyrexia, and maculopapular rash. One patient presented with diarrhea; no cases of colitis were reported. One patient discontinued treatment because of pyrexia and maculopapular rash; two patients died because of disease progression. Conclusion: This study was terminated because factors contributing to safety concerns in phase III studies of idelalisib for hematological malignancies were not fully understood. In this small sample of patients with metastatic PDAC, exposure to idelalisib resulted in safety findings consistent with previous studies, with reduced diarrhea/colitis.
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U2 - 10.1634/theoncologist.2020-0321
DO - 10.1634/theoncologist.2020-0321
M3 - Article
C2 - 32356383
AN - SCOPUS:85087317274
SN - 1083-7159
VL - 25
SP - e1604-e1613
JO - Oncologist
JF - Oncologist
IS - 11
ER -