Presentation is loading. Please wait.

Presentation is loading. Please wait.

XL647—A Multitargeted Tyrosine Kinase Inhibitor: Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding.

Published byBambang Sanjaya Modified over 5 years ago

Similar presentations

Presentation on theme: "XL647—A Multitargeted Tyrosine Kinase Inhibitor: Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding."— Presentation transcript:

1 XL647—A Multitargeted Tyrosine Kinase Inhibitor: Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding to Treatment with Either Gefitinib or Erlotinib  M. Catherine Pietanza, MD, Thomas James Lynch, MD, Primo N. Lara, MD, John Cho, MD, Ronald H. Yanagihara, MD, Nandagopal Vrindavanam, MD, Naveed Mahfooz Chowhan, MD, Shirish M. Gadgeel, MD, Nathan A. Pennell, MD, PhD, Roel Funke, PhD, Ben Mitchell, PhD, Heather A. Wakelee, MD, Vincent A. Miller, MD  Journal of Thoracic Oncology  Volume 7, Issue 1, Pages (January 2012) DOI: /JTO.0b013e31822eebf9 Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Diagram for this phase II trial using XL647 in patients who have progressed after erlotinib or gefitinib. TKI, tyrosine kinase inhibitors; SD, stable disease; CR, complete response; PR, partial response; POD, progression of disease. Journal of Thoracic Oncology 2012 7, DOI: ( /JTO.0b013e31822eebf9) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Waterfall Plot. The best-calculated responses based on measurable lesions for the 33 evaluable patients. Mutation status is based on analysis of available tumors. ‡EGFR-sensitizing mutation is exon 19 deletion for these two patients. Overall response indicated on horizontal axis. *PD, based on appearance of new lesions. EGFR T790M unknown mutation status refers to those patients with tumors harboring EGFR-sensitizing mutations who did not undergo rebiopsy at the time of progression of disease either after the first-generation TKIs or XL647. SD, stable disease; PD, progression of disease; and PR, partial response. Journal of Thoracic Oncology 2012 7, DOI: ( /JTO.0b013e31822eebf9) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

4 FIGURE 3 Tumor mutation analysis. Mutation status was known in 21 patients. ¶Two of twenty-one patients underwent biopsy at diagnosis and after TKI therapy, for a total of 23 tumor specimens. Thirteen patients had tumors sampled before initiating erlotinib or gefitinib. §One patient underwent biopsy before initiating erlotinib or gefitinib and subsequent to disease progression with these first-generation TKIs; the tumor harbored an EGFR exon 21 L858R-activating mutation and a T790M resistance mutation. ‡One patient had tumor sampled before initiating erlotinib or gefitinib and after disease progression with XL647; the tumor harbored an EGFR exon 19 deletion activating mutation and a T790M resistance mutation. Seven patients had tumors sampled only after progression of disease with erlotinib or gefitinib. One patient only underwent biopsy subsequent to disease progression with XL647. A total of eight tumors were found to have T790M mutations. ¥Germline T790M mutation. *This T790M was found in the patient whose primary activating mutation was not detected. EGFR, epidermal growth factor receptor. Journal of Thoracic Oncology 2012 7, DOI: ( /JTO.0b013e31822eebf9) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

5 FIGURE 4 Pharmacokinetics. XL647 accumulated in plasma with repeated daily dosing. Steady state was achieved by about cycle 1 day 15, where the median plasma predose concentration was 439 ng/mL (0.89 μM). Predose and postdose concentrations are shown with the median (yellow bar), interquartile range (box), and range (whiskers). Exposure to XL647 was maintained over repeated cycles of dosing with XL647, as can be seen from the small number of patients with available PK data obtained after three cycles. Journal of Thoracic Oncology 2012 7, DOI: ( /JTO.0b013e31822eebf9) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Download ppt "XL647—A Multitargeted Tyrosine Kinase Inhibitor: Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding."

Similar presentations

A Noninvasive System for Monitoring Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors with Plasma DNA  Tomomi Nakamura, MD, Naoko.

A Noninvasive System for Monitoring Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors with Plasma DNA  Tomomi Nakamura, MD, Naoko.
Prognostic impacts of EGFR mutation status and subtype in patients with surgically resected lung adenocarcinoma  Kazuya Takamochi, MD, Shiaki Oh, MD,

Prognostic impacts of EGFR mutation status and subtype in patients with surgically resected lung adenocarcinoma  Kazuya Takamochi, MD, Shiaki Oh, MD,
Application of a Highly Sensitive Detection System for Epidermal Growth Factor Receptor Mutations in Plasma DNA  Tomomi Nakamura, MD, Naoko Sueoka-Aragane,

Application of a Highly Sensitive Detection System for Epidermal Growth Factor Receptor Mutations in Plasma DNA  Tomomi Nakamura, MD, Naoko Sueoka-Aragane,
Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.

Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.
Phase II Study of Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), and Celecoxib, a Cyclooxygenase-2 (COX-2) Inhibitor,

Phase II Study of Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), and Celecoxib, a Cyclooxygenase-2 (COX-2) Inhibitor,
A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma  Karen L. Reckamp, MD, Vladislava O. Melnikova,

A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma  Karen L. Reckamp, MD, Vladislava O. Melnikova,
Application of a Highly Sensitive Detection System for Epidermal Growth Factor Receptor Mutations in Plasma DNA  Tomomi Nakamura, MD, Naoko Sueoka-Aragane,

Application of a Highly Sensitive Detection System for Epidermal Growth Factor Receptor Mutations in Plasma DNA  Tomomi Nakamura, MD, Naoko Sueoka-Aragane,
Adrian G. Sacher, MD, Kimberly M. Komatsubara, MD, Geoffrey R

Adrian G. Sacher, MD, Kimberly M. Komatsubara, MD, Geoffrey R
Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic.

Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic.
Early Prediction of Response to Tyrosine Kinase Inhibitors by Quantification of EGFR Mutations in Plasma of NSCLC Patients  Antonio Marchetti, MD, PhD,

Early Prediction of Response to Tyrosine Kinase Inhibitors by Quantification of EGFR Mutations in Plasma of NSCLC Patients  Antonio Marchetti, MD, PhD,
Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity 

Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity 
Negative Thyroid Transcription Factor 1 Expression Defines an Unfavorable Subgroup of Lung Adenocarcinomas  Yiliang Zhang, MD, Rui Wang, MD, PhD, Yuan.

Negative Thyroid Transcription Factor 1 Expression Defines an Unfavorable Subgroup of Lung Adenocarcinomas  Yiliang Zhang, MD, Rui Wang, MD, PhD, Yuan.
A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients.

A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients.
Durable Response to Tyrosine Kinase Inhibitor Therapy in a Lung Cancer Patient Harboring Epidermal Growth Factor Receptor Tandem Kinase Domain Duplication 

Durable Response to Tyrosine Kinase Inhibitor Therapy in a Lung Cancer Patient Harboring Epidermal Growth Factor Receptor Tandem Kinase Domain Duplication 
Erlotinib Response in an NSCLC Patient with a Novel Compound G719D+L861R Mutation in EGFR  Eamon M. Berge, MD, Dara L. Aisner, MD, PhD, Robert C. Doebele,

Erlotinib Response in an NSCLC Patient with a Novel Compound G719D+L861R Mutation in EGFR  Eamon M. Berge, MD, Dara L. Aisner, MD, PhD, Robert C. Doebele,
Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Third- Generation EGFR Tyrosine Kinase Inhibitor  Alessandra Bearz, MD, Elisa.

Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Third- Generation EGFR Tyrosine Kinase Inhibitor  Alessandra Bearz, MD, Elisa.
EGFR Molecular Profiling in Advanced NSCLC: A Prospective Phase II Study in Molecularly/Clinically Selected Patients Pretreated with Chemotherapy  Michele.

EGFR Molecular Profiling in Advanced NSCLC: A Prospective Phase II Study in Molecularly/Clinically Selected Patients Pretreated with Chemotherapy  Michele.
Susan C. Scott, MD, Nathan A. Pennell, MD, PhD 

Susan C. Scott, MD, Nathan A. Pennell, MD, PhD 
Association of Epidermal Growth Factor Receptor Activating Mutations with Low ERCC1 Gene Expression in Non-small Cell Lung Cancer  David R. Gandara, MD,

Association of Epidermal Growth Factor Receptor Activating Mutations with Low ERCC1 Gene Expression in Non-small Cell Lung Cancer  David R. Gandara, MD,
Safety and Efficacy of Dacomitinib in Korean Patients with KRAS Wild-Type Advanced Non–Small-Cell Lung Cancer Refractory to Chemotherapy and Erlotinib.

Safety and Efficacy of Dacomitinib in Korean Patients with KRAS Wild-Type Advanced Non–Small-Cell Lung Cancer Refractory to Chemotherapy and Erlotinib.

Similar presentations

Ads by Google