Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Small Cell Lung Carcinoma

Adenocarcinoma

Recurrence

Adenocarcinoma of Lung

Carcinoma

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Cell Lung Cancer

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ponatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive ponatinib hydrochloride taken by mouth once or twice a day. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ponatinib 45mg taken by mouth each day at the same time with or without food

Ross D Camidge, MD, PhD

This phase II trial studies how well ponatinib hydrochloride works in treating patients with stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

This study will look at the safety and effectiveness of the investigational drug ponatinib in lung cancer. The investigators hope that ponatinib will work against tumors that have certain biomarkers. Therefore, the study will pre-screen patients for these certain biomarkers before enrolling them into the main treatment study. Different doses of ponatinib may be tested in this study.

Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

A Phase II Study of Ponatinib in Cohorts of Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

Biomarker prevalence and its 95% (exact) confidence interval (CI) among the screening patients and for different histologies will be reported. Molecular cohorts for ISH and SISH positivity: FGFR1 ISH+/SISH+, FGFR1 ISH+/SISH-, FGFR1 ISH-/SISH+, and FGFR1 ISH-/SISH-

Overlapping frequency and its 95% CI between biomarkers among the screening patients and for different histologies will also be reported.

Evaluated using Fisher's exact test with a descriptive p-value. Summarized using binomial proportions with 95% exact binomial confidence intervals.

Adverse events will be tabulated per participant, per organ, and per visit.

Ariad Pharmaceuticals

University of Colorado, Denver

The number at risk for all-cause mortality is 4 The number at risk for SAE was 4. There were 75% SAEs.

The pre-defined cutpoint for FGFR1 amplification (SISH+) was an average of at least four FGFR1 signals per nucleus (gene copy number) or FGFR1/CEP8 ratio ≥ 2.0.

mRNA in situ hybridization (ISH) was performed on formalin-fixed paraffin embedded (FFPE) tumor tissue using the RNA scope 2.0 assay system. ISH scores were generated and recorded using the following scoring system at 200 × magnification: 0, no staining; 1, one to 3 dots per tumor cell; 2, 4 to 10 dots per tumor cell; 3, more than 10 dots per cell or presence of dot clusters in ≥1% and \< 10% tumor cells; 4, ≥ 10% tumor cells with dot clusters as per the RNA scope system scoring guidelines.18 The pre-defined cutpoint for FGFR1 ISH positivity was a score of 3 or 4 per this scoring system.

Ponatinib SISH+/ISH+

Please see details in Ponatinib SISH+/ISH+ for the definition of SISH positivity and ISH positivity.

Subjects in this group are those with SISH positive and ISH negative.

Ponatinib SISH+/ISH-

Please see details in Ponatinib SISH+/ISH+ for the definition of SISH positivity and ISH positivity.

Subjects in this group with a negative SISH and a positive ISH

Ponatinib SISH-/ISH+

Please see details in Ponatinib SISH+/ISH+ for the definition of SISH positivity and ISH positivity.

Subjects in this group with a negative SISH and a negative ISH

Ponatinib SISH-/ISH-

Total

Age, Continuous

Sex: Female, Male

Smoking PY

Sites of metastases (soft tissue)

Adenoca

Squamous

Small cell

Histology

KRAS

171 subjects were pre-screen consented to request and submit tissue for ISH and SISH scoring. 122 of 171 subjects received ISH/SISH results and of those 122 subjects who received ISH/SISH results, 4 were main consented and enrolled to actual treatment with ponatinib.

Due to poor tolerability and safety concerns regarding ponatinib after treating the first few patients, the study did not reach its accrual target (N\~70) for the treatment portion of this study and could not confirm or refute the null hypothesis (needed a minimum of 12 patients treated). This study prescreened a more heterogeneous population. As a result, all four patients that were enrolled onto the ponatinib treatment arm had either squamous or poorly differentiated lung cancer.

Dr. Ross Camidge

Less than four FGFR1 signals per nucleus (gene copy number) or FGFR1/CEP8 ratio ≥ 2.0

SISH-

At least four FGFR1 signals per nucleus (gene copy number) or FGFR1/CEP8 ratio ≥ 2.0

SISH+

mRNA in situ hybridization with dot clusters per tumor \<1%

ISH-(<1%)

mRNA in situ hybridization with dot clusters 1%=\<per tumor \<10%

ISH+(>=1%)

mRNA in situ hybridization with dot clusters 10%=\<per tumor \<20%

ISH<20%

mRNA in situ hybridization with dot clusters 1per tumor \>=20%

ISH>=20%

171 cases were prescreened. Among them, 122 cases had both SISH and ISH scores reported, one case had only SISH and four cases had only ISH reported, and 44 cases lacked both SISH and ISH scores, resulting in 123 cases with SISH and 126 cases with ISH. Please note that the 126 cases with ISH scores were displayed in two different ways, one was based on ISH\<1% vs \>+1% (columns 3 and 4 above), and the other was based on ISH\<20% vs \>=20% (columns 5 and 6).

Biomarker FGFR1 (ISH/SISH) Score (Part A)

171 subjects were pre-screen consented to request and submit tissue for ISH and SISH scoring. 122 of 171 subjects received ISH/SISH results and of those 122 subjects who received ISH/SISH results, 4 were enrolled to actual treatment with ponatinib. The number reported here are the eligible number of subjects in each pre-defined category.

Overlapping Frequency of FGFR1 (ISH/SISH) Biomarkers (Part A)

A total of 4 subjects were treated, where the 3 SISH-/ISH+ all with RET-, due to the safety concern of ponatinib and the change of inclusion and exclusion criteria.

Objective Response Rate (ORR) Per RECIST v1.1 (Part B)

Grade 3

Gr 3 fibrillation or febrile neutropenia or platelets

Due to the safety warning of Ponatinib and the adjusted inclusion and exclusion criteria, the study only treated 4 subjects in total.

Spots Global Cancer Trial Database for Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

Trial Identification

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Study Description

Keywords

Eligibility

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Contact Details

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