Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adults With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) (HARBOUR)

A Phase 1b Open Label Study Investigating the Safety and Efficacy of Blinatumomab in Combination With Pembrolizumab in Adult Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

The primary objective of the study is to determine the maximum tolerated dose (MTD) of blinatumomab in combination with pembrolizumab in adults with relapsed or refractory (r/r) DLBCL.

Study Overview

• Status: Completed
• Conditions: Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
• Intervention / Treatment: Drug: Blinatumomab; Drug: Pembrolizumab

Detailed Description

The study was planned as 2 parts:

• Part 1 will test the safety of up to 3 different blinatumomab target dose levels in combination with pembrolizumab in a rolling 6 design. A Dose Level Review Team (DLRT) will review the safety data to evaluate possible drug effects and dose-limiting toxicities (DLTs).
• Part 2 will consist of an expansion cohort to assess pharmacokinetics (PK), safety, and preliminary efficacy data at the chosen target dose. The part 2 dose will be determined by the totality of the clinical data from part 1 as determined by the DLRT.

Based on the results from Part 1, a decision was made not to proceed with Part 2 of this study.

Secondary objectives of the study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of blinatumomab in combination with pembrolizumab. Tumor response will be evaluated according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al, 2007). With implementation of Protocol Amendment 5, response will also be assessed according to the Lugano Classification (Cheson et al, 2014). Only participants enrolled after implementation of Protocol Amendment 5 (03 December 2019) will have tumor assessments using the Lugano criteria.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Research Site
    • St Leonards, New South Wales, Australia, 2065
      • Research Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Research Site
    • Geelong, Victoria, Australia, 3220
      • Research Site
    • Melbourne, Victoria, Australia, 3004
      • Research Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Research Site
• France
  • Créteil Cedex, France, 94010
    • Research Site
  • Nantes Cedex 1, France, 44035
    • Research Site
  • Pierre-Benite, France, 69495
    • Research Site
• Germany
  • Heidelberg, Germany, 69120
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Research Site
  • Rotterdam, Netherlands, 3015 CN
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Castilla León
    • Salamanca, Castilla León, Spain, 37007
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08025
      • Research Site
• United States
  • California
    • La Jolla, California, United States, 92093-0960
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29424
      • Research Site
    • Greenville, South Carolina, United States, 29607
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have histologically confirmed diffuse large B-cell lymphoma that is either:
• Refractory after at least one regimen of systemic chemotherapy and/or targeted therapy, or
• In first or later relapse if have received at least 2 systemic regimens since time of diagnosis, or
• Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT) with adequate organ function after proximity to transplantation time exclusions
• Have measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life expectancy of ≥ 12 weeks in the opinion of the Investigator
• Biopsy proven DLBCL (biopsy proven at least at primary diagnosis of DLBCL)

Other Inclusion Criteria May Apply

Exclusion Criteria:

• Richter's transformation (DLBCL arising in the setting of prior chronic lymphocytic leukemia) or primary mediastinal B cell lymphoma (PMBCL)
• History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Has a diagnosis of immunodeficiency or has received systemic steroid therapy (in excess of 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of protocol specified therapy.
• Has undergone prior allogeneic HSCT:
• within the last 5 years OR
• greater than 5 years ago but has active graft versus host disease (GvHD) requiring systemic treatment.
• Has received autologous HSCT within 6 weeks prior to start of treatment.

Other Exclusion Criteria May Apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort Ia: Blinatumomab 9/28 µg/day + Pembrolizumab; Participants received blinatumomab administered as a continuous intravenous infusion (CIVI) for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days then 28 µg/day for the remaining days of treatment. Starting on Day 15 participants also received 200 mg pembrolizumab administered by intravenous (IV) infusion every 3 weeks (Q3W) until disease progression or for up to 35 cycles.	Drug: Blinatumomab; Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.; Other Names: Blincyto; AMG 103; Formerly known as MT103 or bscCD19xCD3; Drug: Pembrolizumab; One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.; Other Names: Keytruda; MK-3475
Experimental: Cohort IIa: Blinatumomab 9/28/56 µg/day + Pembrolizumab; Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 56 µg/day for the remaining days of treatment. Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.	Drug: Blinatumomab; Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.; Other Names: Blincyto; AMG 103; Formerly known as MT103 or bscCD19xCD3; Drug: Pembrolizumab; One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.; Other Names: Keytruda; MK-3475
Experimental: Cohort IIIa: Blinatumomab 9/28/112 µg/day + Pembrolizumab; Participants received blinatumomab administered as a continuous intravenous infusion for 8 weeks followed by a 28-day treatment-free interval. Participants with stable disease or better may have received a second 28-day consolidation cycle. The starting dose of each cycle was 9 µg/day for the first 7 days, 28 µg/day for 7 days then 112 µg/day for the remaining days of treatment. Starting on Day 19 participants also received 200 mg pembrolizumab administered by IV infusion Q3W until disease progression or for up to 35 cycles.	Drug: Blinatumomab; Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.; Other Names: Blincyto; AMG 103; Formerly known as MT103 or bscCD19xCD3; Drug: Pembrolizumab; One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.; Other Names: Keytruda; MK-3475
Experimental: Expansion Cohort; This cohort will test the maximum tolerated dose of blinatumomab in combination with pembrolizumab identified in Part 1 of the study.	Drug: Blinatumomab; Up to 2 cycles of blinatumomab may be given, where cycle 1 lasts 8 weeks, and cycle 2 lasts 28 days. The treatment is given as a continuous intravenous infusion.; Other Names: Blincyto; AMG 103; Formerly known as MT103 or bscCD19xCD3; Drug: Pembrolizumab; One cycle of pembrolizumab is a 200 mg IV injection lasting 30 minutes. One cycle will be given every 3 weeks until disease progression, or for a maximum of 35 cycles.; Other Names: Keytruda; MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities (DLTs)	Dose-limiting toxicities were grade 3-5 adverse events that occurred during the DLT-evaluation period that were judged by the Investigator to be possibly, probably or definitely related to study drug administration. All toxicities were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: Grade 3: Severe or medically significant but not immediately life-threatening.; Grade 4: Life-threatening.; Grade 5: Death.	The DLT evaluation period was 42 days from initiation of pembrolizumab treatment (Day 15 for Cohort Ia and Day 19 for Cohorts IIa and IIIa)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blinatumomab Clearance	Systemic clearance (CL) was calculated as CL=R0/Css,DN; where R0 is the infusion rate (μg/hr) and Css,DN is the dose normalized average Css.	Day 2 for 9 µg/day Css (all cohorts), days 10, 15, 22, 29, and 43 for 28 µg/day Css (Cohort Ia), day 10 for 28 µg/day Css (Cohorts IIa and IIIa), and days 19, 26, and 40 for 56 µg/day and 112 µg/day Css (Cohorts IIa and IIIa respectively).
Objective Response Rate During the First 12 Weeks Using Revised Response Cheson Criteria	Objective response rate is defined as the percentage of participants with either a complete response (CR) or a partial response (PR): CR: Disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy: If fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET) positive before therapy, a residual mass of any size is permitted if it is PET negative; For variably FDG-avid or if a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on computed tomography (CT) to normal size. Spleen or liver should not be palpable and normal size. Bone marrow infiltrate must have cleared or be negative by immunohistochemistry.; PR: Regression of measurable disease and no new sites (≥ 50% decrease in size of up to six of the largest dominant nodes or nodal masses and splenic and hepatic nodules). Participants with no post-baseline response assessments were considered non-responders.	First 12 weeks of blinatumomab treatment
Cohort IIIa Only: Objective Response Rate During the First 12 Weeks Using the Lugano Classification	Objective response rate is defined as the percentage of participants with either a complete metabolic response (CMR) or a partial metabolic response (PMR): CMR: For PET-CT-based response, score of 1-3 on the Deauville five-point scale (5PS) for lymph nodes and extralymphatic sites, no evidence of FDG-avid disease in marrow. For CT-based response, target nodes/masses regress to 1.5 cm in longest transverse diameter, no extralymphatic sites of disease, normal bone marrow morphology; PMR: For PET-CT-based response, score of 4 or 5 on 5PS with reduced uptake compared to baseline for lymph nodes and extralymphatic sites, residual uptake reduced compared to baseline in the bone marrow. For CT-based response, ≥ 50% decrease in sum of the product of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites, spleen must have regressed by > 50% in length beyond normal. Participants with no post-baseline response assessments were considered non-responders.	First 12 weeks of blinatumomab treatment
Objective Response Rate During the Treatment Period Using Revised Response Cheson Criteria	Objective response rate is defined as the percentage of participants with either a CR or a PR according to the Revised Response Criteria (2007): CR: Disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy: If FDG-avid or PET positive before therapy, a residual mass of any size is permitted if it is PET negative; For variably FDG-avid or if a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. Spleen or liver should not be palpable and normal size. Bone marrow infiltrate must have cleared or be negative by immunohistochemistry.; PR: Regression of measurable disease and no new sites (≥ 50% decrease in size of up to six of the largest dominant nodes or nodal masses and splenic and hepatic nodules). Participants with no post-baseline response assessments were considered non-responders.	From Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Cohort IIIa Only: Objective Response Rate During the Treatment Period Using the Lugano Classification	Objective response rate is defined as the percentage of participants with either a CMR or a CMR.; CMR: For PET-CT-based response, score of 1-3 on the Deauville 5PS for lymph nodes and extralymphatic sites, no evidence of FDG-avid disease in marrow. For CT-based response, target nodes/masses regress to 1.5 cm in longest transverse diameter, no extralymphatic sites of disease, normal bone marrow morphology; PMR: For PET-CT-based response, score of 4 or 5 on 5PS with reduced uptake compared to baseline for lymph nodes and extralymphatic sites, residual uptake reduced compared to baseline in the bone marrow. For CT-based response, ≥ 50% decrease in sum of the product of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites, spleen must have regressed by > 50% in length beyond normal. Participants with no post-baseline response assessments were considered non-responders.	From study Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Complete Response Rate During the First 12 Weeks Using the Revised Response Cheson Criteria	Complete response rate is defined as the percentage of participants with a CR according to the Revised Response Criteria (2007): - CR: Disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy: If FDG-avid or PET positive before therapy, a residual mass of any size is permitted if it is PET negative; For variably FDG-avid or if a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. Spleen or liver should not be palpable and normal size. Bone marrow infiltrate must have cleared or be negative by immunohistochemistry. Participants with no post-baseline response assessments were considered non-responders.	First 12 weeks of blinatumomab treatment
Cohort IIIa Only: Complete Response Rate During the First 12 Weeks Using the Lugano Classification	Complete response rate is defined as the percentage of participants with a CMR according to the Lugano classification (2014): CMR: For PET-CT-based response, score of 1-3 on the Deauville 5PS for lymph nodes and extralymphatic sites, no evidence of FDG-avid disease in marrow. For CT-based response, target nodes/masses regress to 1.5 cm in longest transverse diameter, no extralymphatic sites of disease, normal bone marrow morphology. Participants with no post-baseline response assessments were considered non-responders.	First 12 weeks of blinatumomab treatment
Complete Response Rate During the Treatment Period Using the Revised Response Cheson Criteria	Complete response rate is defined as the percentage of participants with a complete response according to the Revised Response Criteria (2007): - CR: Disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy: If FDG-avid or PET positive before therapy, a residual mass of any size is permitted if it is PET negative; For variably FDG-avid or if a pretreatment PET scan was negative, all lymph nodes and nodal masses must have regressed on CT to normal size. Spleen or liver should not be palpable and normal size. Bone marrow infiltrate must have cleared or be negative by immunohistochemistry. Participants with no post-baseline response assessments were considered non-responders.	From Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Cohort IIIa Only: Complete Response Rate During the Treatment Period Using the Lugano Classification	Complete response rate is defined as the percentage of participants with a CMR according to the Lugano classification (2014): - CMR: For PET-CT-based response, score of 1-3 on the Deauville 5PS for lymph nodes and extralymphatic sites, no evidence of FDG-avid disease in marrow. For CT-based response, target nodes/masses regress to 1.5 cm in longest transverse diameter, no extralymphatic sites of disease, normal bone marrow morphology. Participants with no post-baseline response assessments were considered non-responders.	From Day 1 to 30 days after last dose of either blinatumomab or pembrolizumab administration; the overall median duration of treatment was 87 days.
Progression Free Survival by the Revised Response Cheson Criteria	Progression-free survival was calculated as the time from the date of the first dose of blinatumomab until the date of diagnosis of progression of lymphoma using the Cheson revised response criteria (2007), or date of death, whichever was earliest. Participants who were alive and did not have progression were censored at the last radiological non-missing evaluable tumor assessment date. Progressive disease per the revised response criteria is any new lesion or increase of 50% or greater in size of nodal masses or lesions or new or recurrent nodal involvement.	From first dose of blinatumomab up to the end of study. Median (min, max) time on study was 188.0 days (19.0, 1512.0).
Cohort IIIa Only: Progression Free Survival Using the Lugano Classification	Progression-free survival was calculated as the time from the date of the first dose of blinatumomab until the date of diagnosis of progression of lymphoma using the Lugano 2014 classification, or date of death, whichever was earliest. For diagnosis of progression of lymphoma, the progression of radiographic assessment of PET-CT using the Lugano Classification was used. Participants who were alive and did not have progression were censored at the last radiological non-missing evaluable tumor assessment date. Progressive disease per the Lugano criteria is a score of 4 or 5 on the 5PS with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma.	From first dose of blinatumomab up to the end of study. Median (min, max) time on study was 188.0 days (19.0, 1512.0).
Overall Survival	Overall survival was calculated as the time from the date of first dose of blinatumomab until death due to any cause. Participants who were alive at the analysis date were censored at the date last known to be alive.	From first dose of blinatumomab up to the end of study. Median (min, max) time on study was 188.0 days (19.0, 1512.0).
Duration of Response for Participants Who Achieved CR/PR Using the Revised Response Cheson Criteria	Duration of response was calculated from the date a response of CR or PR was first achieved until the earliest date of a disease assessment indicating a disease progression or death, whichever occurred first. Participants who did not have a relapse event were censored on their last radiological non-missing evaluable tumor assessment date.	From first dose of blinatumomab up to the end of study. Median (min, max) time on study was 188.0 days (19.0, 1512.0).
Cohort IIIa Only: Duration of Response for Participants Who Achieved CMR/PMR Using the Lugano Classification	The duration of response was calculated from the date a response of CMR or PMR was first achieved until the earliest date of a disease assessment indicating a disease progression using the Lugano classification or death, whichever occurred first. Participants who did not have a relapse event were censored on their last radiological non-missing evaluable tumor assessment date.	From first dose of blinatumomab up to the end of study. Median (min, max) time on study was 188.0 days (19.0, 1512.0).
Blinatumomab Steady State Concentration (Css)	Serum blinatumomab concentrations were quantified using a validated enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) for the assay is 50 pg/mL. The Css of serum blinatumomab was summarized as the average of the observed concentrations collected after 24 hours from the start of continuous IV infusion or start of the dose step. For calculation of Css at 9 µg/day and 28 µg/day dosing, participants in all cohorts were combined.	Day 2 for 9 µg/day Css (all cohorts), days 10, 15, 22, 29, and 43 for 28 µg/day Css (Cohort Ia), day 10 for 28 µg/day Css (Cohorts IIa and IIIa), and days 19, 26, and 40 for 56 µg/day and 112 µg/day Css (Cohorts IIa and IIIa respectively).
Pembrolizumab Peak Serum Concentration	Pembrolizumab serum concentrations were quantified using a validated electro-chemiluminescent-based immunoassay with a lower limit of quantification of 25 ng/mL. The pembrolizumab pharmacokinetic data from all cohorts were combined for analysis.	Within approximately 30 minutes after the end of the infusion in cycle 1 (study day 15 for Cohort Ia, study day 19 for Cohorts IIa and IIIa) and cycle 8 (study day 162 for Cohort Ia and day 166 for Cohorts IIa and IIIa).
Pembrolizumab Minimum Serum Concentration	Pembrolizumab serum concentrations were quantified using a validated electrochemiluminescent-based immunoassay with a lower limit of quantification of 25 ng/mL. The pembrolizumab pharmacokinetic data from all cohorts were combined for analysis.	Pre-dose on pembrolizumab cycles 2, 4, 6, 8, and 12 (Study days 36, 78, 120, 162, and 246, respectively).
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A TEAE was defined as any untoward medical occurrence in a clinical trial participant that started after the initiation of blinatumomab. All TEAEs were graded using NCI CTCAE Version 4.0: Grade 2: Moderate; Grade 3: Severe or medically significant but not immediately life-threatening.	From first dose of blinatumomab to minimum of 30 days after last dose of blinatumomab or pembrolizumab (whichever was later) or end of study: median (min, max) duration was 22.7 (1.0, 85.8) days.

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2018
• Primary Completion (Actual): November 6, 2020
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Antibodies; DLBCL Relapsed post-autologous or allogeneic hematopoietic stem cell transplantation (HSCT); Bispecific in combination with PD-1/PD-L1 inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Blinatumomab
• Other Study ID Numbers: 20150290; 2016-002191-27 (EudraCT Number); PN348 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No