Tolerability and Efficacy of Tremelimumab in Combination With Gefitinib in NSCLC Patients (GEFTREM)
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|ClinicalTrials.gov Identifier: NCT02040064|
Recruitment Status : Completed
First Posted : January 20, 2014
Last Update Posted : June 9, 2016
This is an open-label phase 1, safety, PK, and preliminary efficacy study of oral Gefitinib and IV Tremelimumab in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as Erlotinib or Gefitinib. The primary objective of this phase I, is to determine the safety and tolerability of oral Gefitinib in combination with escalating doses of Tremelimumab and to establish a recommended phase 2 dose. Secondary objectives include evaluation of, pharmacokinetics, immunogenicity, antitumor activity of Gefitinib and Tremelimumab combination. The exploratory objectives are to evaluate biomarkers that may correlate with activity or prospectively identify patients likely to respond to Tremelimumab and Gefitinib.
The biological rationale for such a study is that even though the disease is progressing it is likely that EGFR sensitive clones, although diminished under the pressure from the EGFR TKI, are still present. Therefore, withdrawing the inhibitory pressure of the EGFR TKI can potentially allow regrowth of the EGFR sensitive cells. On the other hand, the proliferation of EGFR resistant clones needs to be suppressed by another therapeutic approach. Until today no association of chemotherapy and TKI EGFR has demonstrated clinical benefit. Moreover, patients may have received chemotherapy and the likelihood of chemosensitivity is very low. So, the association of Gefitinib with immune checkpoint blockade is very attractive and may result in clinical benefit in NSCLC with EGFRmut.
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer||Drug: Gefitinib Drug: Tremelimumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I, Open-label, Safety, Tolerability and Preliminary Efficacy Study of Tremelimumab in Combination With Gefitinib in EGFR Mutant NSCLC Patients|
|Study Start Date :||January 2014|
|Actual Primary Completion Date :||March 2016|
|Actual Study Completion Date :||March 2016|
- safety and tolerability of the association between Gefitinib (fixed dose) and Tremelimumab (dose escalation) [ Time Frame: Up to 42 days ]The primary objective of this phase 1 study is to determine the safety and tolerability of oral Gefitinib in combination with three escalating doses of Tremelimumab and to establish a recommended phase 2 dose. Overall safety profile will be characterized by type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCICTCAE] Version 4.03), timing of adverse events and laboratory abnormalities in the first and in the following cycles
- Anti-tumour activity of Gefitinib + Tremelimumab [ Time Frame: From day 1 cycle 1 every 8 weeks for 24 weeks and then every 6 weeks until progression or death whichever comes first assessed up to 30 months ]To obtain a preliminary assessment of the anti-tumour activity of Gefitinib + Tremelimumab by evaluation of tumour response using modified Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and evaluation of Disease control rate and PFS
- Immunogenicity of Tremelimumab in combination with Gefitinib [ Time Frame: At day 1 cycle 1 and then every 8 weeks from day 1 cycle 2 until progression or death whichever comes first assessed up to 30 months ]Immunogenicity results will be analyzed descriptively by summarizing the number and percentage of subjects who develop detectable anti-Tremelimumab antibodies. The immunogenicity titer will be reported for samples confirmed positive for the presence of anti-Tremelimumab antibodies.
- Pharmacokinetics of Gefitinib [ Time Frame: At first Tremelimumab administration and then every 4 weeks until progression or death whichever comes first assessed up to 30 months ]Gefitinib pharmacokinetic parameters comprise the area under the curve from time t0 to t (AUC0-t), AUC from time t0 to the infini (AUC0-∞) and maximal concentration (Cmax)
- Pharmacokinetics of Tremelimumab [ Time Frame: Before and after injection of Tremelimumab at day 1 cycle 1 and at day 8 and day 15 of cycle 1 and then before and after injection at day 1 for every cycle (4 weeks) until progression or death whichever comes first assessed up to 30 months ]Tremelimumab pharmacokinetic parameters comprise the area under the curve from time t0 to t (AUC0-t), AUC from time t0 to the infini (AUC0-∞) and maximal concentration (Cmax)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02040064
|Villejuif, Val de Marne, France, 94805|
|Study Chair:||David Planchard, MD||Gustave Roussy, Cancer Campus, Grand Paris|