SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)

Corey J. Langer, Mary W. Redman, James L. Wade, Charu Aggarwal, Jeffrey D. Bradley, Jeffrey Crawford, Philip J. Stella, Mark H. Knapp, Jieling Miao, Katherine Minichiello, Roy S. Herbst, Karen Kelly, David R Gandara, Vassiliki A. Papadimitrakopoulou

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: S1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC). Methods: Eligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response. Results: Twenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53–83 years), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% response rate, 95% confidence interval [CI]: 0%–24%). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95% CI: 1.8–4.0 mo) and 5.9 months (95% CI: 4.2–7.8 mo), respectively. These numbers were nearly the same in the FEP. Conclusions: Study S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - Jan 1 2019

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Phosphatidylinositol 3-Kinase
Squamous Cell Neoplasms
Lung Neoplasms
Medical Futility
Population
Confidence Intervals
Disease-Free Survival
Cataloging
Mutation
Survival
2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide
Heart Arrest
Platinum
Population Groups
Respiratory Insufficiency
Disease Progression
Catalytic Domain
Biomarkers
Lung

Keywords

  • Lung cancer
  • Master protocol
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study). / Langer, Corey J.; Redman, Mary W.; Wade, James L.; Aggarwal, Charu; Bradley, Jeffrey D.; Crawford, Jeffrey; Stella, Philip J.; Knapp, Mark H.; Miao, Jieling; Minichiello, Katherine; Herbst, Roy S.; Kelly, Karen; Gandara, David R; Papadimitrakopoulou, Vassiliki A.

In: Journal of Thoracic Oncology, 01.01.2019.

Research output: Contribution to journalArticle

Langer, Corey J. ; Redman, Mary W. ; Wade, James L. ; Aggarwal, Charu ; Bradley, Jeffrey D. ; Crawford, Jeffrey ; Stella, Philip J. ; Knapp, Mark H. ; Miao, Jieling ; Minichiello, Katherine ; Herbst, Roy S. ; Kelly, Karen ; Gandara, David R ; Papadimitrakopoulou, Vassiliki A. / SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study). In: Journal of Thoracic Oncology. 2019.
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abstract = "Background: S1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC). Methods: Eligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response. Results: Twenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53–83 years), 19 were male (73{\%}). The study was closed for futility at interim analysis with one responder in the PAP (5{\%} response rate, 95{\%} confidence interval [CI]: 0{\%}–24{\%}). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95{\%} CI: 1.8–4.0 mo) and 5.9 months (95{\%} CI: 4.2–7.8 mo), respectively. These numbers were nearly the same in the FEP. Conclusions: Study S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC.",
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AU - Langer, Corey J.

AU - Redman, Mary W.

AU - Wade, James L.

AU - Aggarwal, Charu

AU - Bradley, Jeffrey D.

AU - Crawford, Jeffrey

AU - Stella, Philip J.

AU - Knapp, Mark H.

AU - Miao, Jieling

AU - Minichiello, Katherine

AU - Herbst, Roy S.

AU - Kelly, Karen

AU - Gandara, David R

AU - Papadimitrakopoulou, Vassiliki A.

PY - 2019/1/1

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N2 - Background: S1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC). Methods: Eligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response. Results: Twenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53–83 years), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% response rate, 95% confidence interval [CI]: 0%–24%). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95% CI: 1.8–4.0 mo) and 5.9 months (95% CI: 4.2–7.8 mo), respectively. These numbers were nearly the same in the FEP. Conclusions: Study S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC.

AB - Background: S1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC). Methods: Eligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response. Results: Twenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53–83 years), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% response rate, 95% confidence interval [CI]: 0%–24%). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95% CI: 1.8–4.0 mo) and 5.9 months (95% CI: 4.2–7.8 mo), respectively. These numbers were nearly the same in the FEP. Conclusions: Study S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC.

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KW - Master protocol

KW - Targeted therapy

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