A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer

Jean Charles Soria, Alex Adjei, Rastilav Bahleda, Benjamin Besse, Charles Ferte, David Planchard, Jing Zhou, Joseph Ware, Kari Morrissey, Geetha Shankar, Wei Lin, Jennifer L. Schutzman, Grace K. Dy, Harry J.M. Groen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aim The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. Patients and methods A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. Results All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a ‘14 days on, 7 days off’ schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. Conclusion Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.

Original languageEnglish (US)
Pages (from-to)186-196
Number of pages11
JournalEuropean Journal of Cancer
Volume86
DOIs
StatePublished - Nov 1 2017

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Pemetrexed
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Cisplatin
Pharmacokinetics
Safety
Phosphatidylinositol 3-Kinase
Maximum Tolerated Dose
Standard of Care
Bevacizumab
Time and Motion Studies
Tablets
Capsules
Histology
Appointments and Schedules

Keywords

  • Bevacizumab
  • Carboplatin
  • Cisplatin
  • First-line NSCLC
  • Front-line NSCLC
  • Metastatic NSCLC
  • Non–small cell lung
  • Paclitaxel
  • Pemetrexed
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer. / Soria, Jean Charles; Adjei, Alex; Bahleda, Rastilav; Besse, Benjamin; Ferte, Charles; Planchard, David; Zhou, Jing; Ware, Joseph; Morrissey, Kari; Shankar, Geetha; Lin, Wei; Schutzman, Jennifer L.; Dy, Grace K.; Groen, Harry J.M.

In: European Journal of Cancer, Vol. 86, 01.11.2017, p. 186-196.

Research output: Contribution to journalArticle

Soria, Jean Charles ; Adjei, Alex ; Bahleda, Rastilav ; Besse, Benjamin ; Ferte, Charles ; Planchard, David ; Zhou, Jing ; Ware, Joseph ; Morrissey, Kari ; Shankar, Geetha ; Lin, Wei ; Schutzman, Jennifer L. ; Dy, Grace K. ; Groen, Harry J.M. / A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer. In: European Journal of Cancer. 2017 ; Vol. 86. pp. 186-196.
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title = "A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer",
abstract = "Aim The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. Patients and methods A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. Results All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4{\%}), 56 (84.8{\%}) and 9 (13.6{\%}) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a ‘14 days on, 7 days off’ schedule. The best confirmed response was partial response in 29 (43.9{\%}) patients and stable disease in 20 (30.9{\%}) patients. Conclusion Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.",
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T1 - A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non–small cell lung cancer

AU - Soria, Jean Charles

AU - Adjei, Alex

AU - Bahleda, Rastilav

AU - Besse, Benjamin

AU - Ferte, Charles

AU - Planchard, David

AU - Zhou, Jing

AU - Ware, Joseph

AU - Morrissey, Kari

AU - Shankar, Geetha

AU - Lin, Wei

AU - Schutzman, Jennifer L.

AU - Dy, Grace K.

AU - Groen, Harry J.M.

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N2 - Aim The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. Patients and methods A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. Results All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a ‘14 days on, 7 days off’ schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. Conclusion Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.

AB - Aim The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non–small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. Patients and methods A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1–14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. Results All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a ‘14 days on, 7 days off’ schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. Conclusion Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed.

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KW - Front-line NSCLC

KW - Metastatic NSCLC

KW - Non–small cell lung

KW - Paclitaxel

KW - Pemetrexed

KW - Phosphatidylinositol 3-kinase

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