Clinical trial NCT02403271: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2015-03-31
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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.
timeFrame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
measure: 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.
timeFrame: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Secondary outcomes:
measure: Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
timeFrame: 0hr, 1hr, 2hr, and 4hr post-dose
measure: Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
timeFrame: 0hr, 1hr, 2hr, and 4hr post-dose
measure: Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
timeFrame: 60 minutes post-dose (dose administered as an infusion over a 1 hour period)
measure: Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
timeFrame: Pre-dose
measure: Phase 1b: Pharmacodynamics
timeFrame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
measure: Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
timeFrame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
measure: Phase 2: Pharmacodynamics
timeFrame: Pre-dose
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Hackensack
country: United States
state: New Jersey
city: Durham
country: United States
state: North Carolina
city: Germantown
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Pharmacyclics LLC.
name: Isaiah Dimery
role: STUDY_DIRECTOR
References: