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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 | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer |
Vol | 14 |
Issue | 10 |
Date | 2019 Oct |
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. |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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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: 26366557), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Nov 2020). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA M1043I did not demonstrated response (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA E453K did not demonstrated response (PMID: 31158500; NCT02785913). | 31158500 |
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, none of the 4 patients harboring PIK3CA H1047R demonstrated response (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, a patients harboring PIK3CA G1047R did not demonstrated response (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, with only 1 responder in the primary analysis population (n=21) (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, none of the 6 patients harboring PIK3CA E542K demonstrated response (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, only 1 of the 11 patients harboring PIK3CA E545K demonstrated response (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 primary endpoint in patients with lung squamous cell carcinoma harboring PIK3CA mutations, none of the 2 patients harboring PIK3CA N345K demonstrated response (PMID: 31158500; NCT02785913). | 31158500 |