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

NCT02403271 | Completed Phase 1 Results DMC

• 1 other identifier: PCYC-1135-CA
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 17

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (7)

• Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib

  0hr, 1hr, 2hr, and 4hr post-dose

• Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib

  0hr, 1hr, 2hr, and 4hr post-dose

• Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)

  60 minutes post-dose (dose administered as an infusion over a 1 hour period)

• Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)

  Pre-dose

• Phase 1b: Pharmacodynamics

  From the date of first study treatment until DLT or disease progression per RECIST 1.1.

Study Arms (2)

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).

Drug: Ibrutinib; Drug: Durvalumab

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.

Drug: Ibrutinib; Drug: Durvalumab

Interventions

Ibrutinib DRUG

BTK Inhibitor

Also known as: PCI-32765

Phase 1b; Phase 2

Durvalumab DRUG

Anti PDL-1

Also known as: MEDI4736

Phase 1b; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pharmacyclics LLC.: lead

Study Sites (17)

Unknown Facility

Birmingham, Alabama, 35294, United States

Location

Unknown Facility

Scottsdale, Arizona, 85258, United States

Location

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

Los Angeles, California, 90025, United States

Location

Unknown Facility

Los Angeles, California, 90048, United States

Location

Unknown Facility

Palo Alto, California, 94305, United States

Location

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

Gainesville, Florida, 32610, United States

Location

Unknown Facility

Orlando, Florida, 32806, United States

Location

Unknown Facility

Chicago, Illinois, 60637, United States

Location

Unknown Facility

Peoria, Illinois, 61615, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Germantown, Tennessee, 38120, United States

Location

Unknown Facility

Nashville, Tennessee, 37212, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Pancreatic Neoplasms; Lung Neoplasms

Interventions

ibrutinib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Thorsten Graef
• Organization: Pharmacyclics LLC, An AbbVie Company

tgraef@pcyc.com

(408) 215-3127

Study Officials

• Isaiah Dimery

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 31, 2015
• Study Start: March 1, 2015
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: January 3, 2019
• Results First Posted: January 3, 2019

Record last verified: 2018-12

Locations

US (17)