Tolerability and Efficacy of Tremelimumab in Combination With Gefitinib in NSCLC Patients

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT02040064
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Jan 31, 2014
Status verified
Jun 2016
Primary completion
Mar 31, 2016
Completion
Mar 31, 2016

Study Design

Enrollment
27 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment
    * Cohort 1: Tremelimumab 3 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 3 mg/kg is the MTD) * Cohort 2: Tremelimumab 6 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 6 mg/kg is the MTD) * Cohort 3: Tremelimumab 10 mg/kg every 4 Weeks plus Gefitinib 250 mg/daily, 6 patients (+ 6 patients if 10 mg/kg is the MTD)

Primary Outcome Measure

safety and tolerability of the association between Gefitinib (fixed dose) and Tremelimumab (dose escalation) [ Time Frame: Up to 42 days ]

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