Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
PCYC-1135-CA
- NCT ID:
NCT02403271
Conditions
- Non-Small Cell Lung Cancer
- Breast Cancer
- Pancreatic Cancer
Interventions
Drug | Synonyms | Arms |
---|
Ibrutinib | PCI-32765 | Phase 1b |
Durvalumab | MEDI4736 | Phase 1b |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1b | Experimental | 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). | |
Phase 2 | Experimental | 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. | |
Eligibility Criteria
Inclusion Criteria:
1. Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or
squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic
Cancer (adenocarcinoma)
2. 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.
3. Measurable lesion by RECIST 1.1
4. Adequate hematologic function:
- ANC >1500 cells/mm3
- Platelet count >100,000 cells/mm3
- HGB >9.0 g/dL
5. 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)
6. PT/INR <1.5 x ULN and PTT/ aPTT <1.5 x ULN
Exclusion Criteria:
1. Mixed small cell and NSCLC histology
2. 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.
3. Anti-tumor therapy within 21 days of study Day 1
4. 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.
5. History of allogeneic organ transplant
6. Treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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. |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib |
Time Frame: | 0hr, 1hr, 2hr, and 4hr post-dose |
Safety Issue: | |
Description: | Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1. |
Measure: | Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib |
Time Frame: | 0hr, 1hr, 2hr, and 4hr post-dose |
Safety Issue: | |
Description: | AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1 |
Measure: | Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736) |
Time Frame: | 60 minutes post-dose (dose administered as an infusion over a 1 hour period) |
Safety Issue: | |
Description: | Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1. |
Measure: | Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736) |
Time Frame: | Pre-dose |
Safety Issue: | |
Description: | Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1 |
Measure: | Phase 1b: Pharmacodynamics |
Time Frame: | From the date of first study treatment until DLT or disease progression per RECIST 1.1. |
Safety Issue: | |
Description: | BTK occupancy |
Measure: | 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. |
Safety Issue: | |
Description: | |
Measure: | Phase 2: Pharmacodynamics |
Time Frame: | Pre-dose |
Safety Issue: | |
Description: | BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Pharmacyclics LLC. |
Trial 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
Last Updated
January 3, 2019