Back to resultsA Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
Primary Purpose
Non-Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ibrutinib
Durvalumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Pharmacyclics, PCYC, Ibrutinib, Durvalumab (MEDI4736), Relapsed Refractory Solid Tumor, Non-Small Cell Lung Cancer, NSCLC, Squamous, Squamous NSCLC, Squamous Non-Small Cell Lung Cancer, Immunotherapy, IMBRUVICA®, Tumor Immunotherapy, Anti-PD-L1, Lung Cancer, Breast Cancer, Triple Negative, HER2 Positive, HER2 + Breast Cancer, Pancreatic Cancer
Eligibility Criteria
Inclusion Criteria:
- Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic Cancer (adenocarcinoma)
- Relapsed or refractory disease (Stage III or IV): NSCLC or pancreatic cancer must have failed at least 1 prior treatment. Breast cancer must have failed at least 2 prior treatments.
- Measurable lesion by RECIST 1.1
Adequate hematologic function:
- ANC >1500 cells/mm3
- Platelet count >100,000 cells/mm3
- HGB >9.0 g/dL
Adequate hepatic and renal function:
- AST and ALT ≤2.5 x ULN for subjects without liver metastases and ≤3.5 x ULN for subjects with liver metastases
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Creatinine ≤2.0 x ULN and Creatinine Clearance ≥40 mL/min (Cockcroft-Gault or 24-hour creatinine clearance collection)
- PT/INR <1.5 x ULN and PTT/ aPTT <1.5 x ULN
Exclusion Criteria:
- Mixed small cell and NSCLC histology
- A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
- Anti-tumor therapy within 21 days of study Day 1
- Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
- History of allogeneic organ transplant
- Treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase 1b
Phase 2
Arm Description
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.
Outcomes
Primary Outcome Measures
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
Secondary Outcome Measures
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
Phase 1b: Pharmacodynamics
BTK occupancy
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
Phase 2: Pharmacodynamics
BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02403271
Brief Title
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
Official Title
A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
August 2017 (Actual)
Study Completion Date
August 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer, Breast Cancer, Pancreatic Cancer
Keywords
Pharmacyclics, PCYC, Ibrutinib, Durvalumab (MEDI4736), Relapsed Refractory Solid Tumor, Non-Small Cell Lung Cancer, NSCLC, Squamous, Squamous NSCLC, Squamous Non-Small Cell Lung Cancer, Immunotherapy, IMBRUVICA®, Tumor Immunotherapy, Anti-PD-L1, Lung Cancer, Breast Cancer, Triple Negative, HER2 Positive, HER2 + Breast Cancer, Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
124 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b
Arm Type
Experimental
Arm Description
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
PCI-32765
Intervention Description
BTK Inhibitor
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
MEDI4736
Intervention Description
Anti PDL-1
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
Time Frame
From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Title
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
Time Frame
From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Secondary Outcome Measure Information:
Title
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
Description
Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
Time Frame
0hr, 1hr, 2hr, and 4hr post-dose
Title
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
Description
AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
Time Frame
0hr, 1hr, 2hr, and 4hr post-dose
Title
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
Description
Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
Time Frame
60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Title
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
Description
Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
Time Frame
Pre-dose
Title
Phase 1b: Pharmacodynamics
Description
BTK occupancy
Time Frame
From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Title
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
Time Frame
From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Title
Phase 2: Pharmacodynamics
Description
BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Time Frame
Pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic Cancer (adenocarcinoma)
Relapsed or refractory disease (Stage III or IV): NSCLC or pancreatic cancer must have failed at least 1 prior treatment. Breast cancer must have failed at least 2 prior treatments.
Measurable lesion by RECIST 1.1
Adequate hematologic function:
ANC >1500 cells/mm3
Platelet count >100,000 cells/mm3
HGB >9.0 g/dL
Adequate hepatic and renal function:
AST and ALT ≤2.5 x ULN for subjects without liver metastases and ≤3.5 x ULN for subjects with liver metastases
Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
Creatinine ≤2.0 x ULN and Creatinine Clearance ≥40 mL/min (Cockcroft-Gault or 24-hour creatinine clearance collection)
PT/INR <1.5 x ULN and PTT/ aPTT <1.5 x ULN
Exclusion Criteria:
Mixed small cell and NSCLC histology
A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
Anti-tumor therapy within 21 days of study Day 1
Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
History of allogeneic organ transplant
Treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isaiah Dimery
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
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