A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors

Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02403271
• Other study ID #: PCYC-1135-CA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2015
• Est. completion date: August 2017

Study information

• Verified date: December 2018
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Ibrutinib
BTK Inhibitor
• Durvalumab
Anti PDL-1

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Primary	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.		From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Secondary	Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib	Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.	0hr, 1hr, 2hr, and 4hr post-dose
Secondary	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	0hr, 1hr, 2hr, and 4hr post-dose
Secondary	Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)	Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.	60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Secondary	Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)	Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1	Pre-dose
Secondary	Phase 1b: Pharmacodynamics	BTK occupancy	From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Secondary	Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)		From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Secondary	Phase 2: Pharmacodynamics	BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.	Pre-dose