Reference Detail

Ref Type

Journal Article

PMID

(31158500)

Authors

Langer CJ, Redman MW, Wade JL, Aggarwal C, Bradley JD, Crawford J, Stella PJ, Knapp MH, Miao J, Minichiello K, Herbst RS, Kelly K, Gandara DR, Papadimitrakopoulou VA

Title

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).

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer	14	10	2019 Oct	1839-1846	J Thorac Oncol

URL

Abstract Text

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).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.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.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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
PIK3CA	H1047Q	missense	unknown	PIK3CA H1047Q is a hotspot mutation that lies within the PI3K/PI4K domain of the Pik3ca protein (UniProt.org). H1047Q has been identified in sequencing studies (PMID: 31158500, PMID: 30547809, PMID: 35880223), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Dec 2023).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA H1047R	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no responses in patients harboring PIK3CA H1047R (n=4) (PMID: 31158500; NCT02785913).	31158500
PIK3CA E542K	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no responses in patients harboring PIK3CA E542K (n=6) (PMID: 31158500; NCT02785913).	31158500
PIK3CA E453K	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in a patient harboring PIK3CA E453K (PMID: 31158500; NCT02785913).	31158500
PIK3CA G1049R	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in a patient harboring PIK3CA G1049R (PMID: 31158500; NCT02785913).	31158500
PIK3CA M1043I	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in a patient harboring PIK3CA M1043I (PMID: 31158500; NCT02785913).	31158500
PIK3CA mutant	lung squamous cell carcinoma	no benefit	Taselisib	Phase I	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in only 1 response in the primary analysis population (n=21) (PMID: 31158500; NCT02785913).	31158500
PIK3CA N345K	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in no response in two patients harboring PIK3CA N345K (PMID: 31158500; NCT02785913).	31158500
PIK3CA E545K	lung squamous cell carcinoma	no benefit	Taselisib	Case Reports/Case Series	Actionable	In a Phase I (SWOG S1400B) trial, Taselisib (GDC-0032) treatment did not meet its primary endpoint for response rate in patients with lung squamous cell carcinoma harboring PIK3CA mutations, resulting in only 1 response of 11 patients harboring PIK3CA E545K (PMID: 31158500; NCT02785913).	31158500