- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03688152
A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma
A Phase 1b, Multicenter, Open-Label Study of the Safety and Tolerability of INCB053914 in Combination With INCB050465 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Tucson, Arizona, United States, 85719
- University of Arizona Cancer Center
-
-
California
-
Santa Monica, California, United States, 90404
- UCLA Healthcare Hematology-Oncology
-
-
New York
-
Lake Success, New York, United States, 11042
- Clinical Research Alliance
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Relapsed or refractory DLBCL, which has been histologically documented, defined as having received at least 2 but no more than 5 prior systemic treatment regimens (eg, an anti-CD20 antibody, an anti-CD20 antibody with or without chemotherapy, or chemotherapy alone) and ineligible for further treatment with standard of care.
- Willing to undergo pretreatment and on-treatment incisional or excisional biopsy of nontarget adenopathy or extranodal lesions. Provision of the most recent, available archived tumor biopsy may satisfy the pretreatment biopsy.
Measurable disease as defined by the Lugano classification criteria:
- ≥ 1 measurable nodal lesion (≥ 1.5 cm in longest dimension) or ≥ 1 measurable extranodal lesion (> 1 cm in longest dimension) on CT scan or MRI
- ≥ 1 PET-avid lesion.
- Eastern Cooperative Oncology Group performance status 0 to 2.
- Willingness to avoid pregnancy or fathering children based on protocol-defined the criteria.
Exclusion Criteria:
- Laboratory values outside the protocol-defined range at screening unless approved by the medical monitor.
- Primary mediastinal (thymic) large B-cell lymphoma or Richter's Syndrome.
- Known brain or central nervous system metastases or history of uncontrolled seizures.
- Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
- Allogeneic stem cell transplant within the last 6 months, or active graft-versus-host disease following allogeneic transplant, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment.
- Use of immunosuppressive therapy following allogenic transplant within 28 days of the first dose of study treatment.
- Prior treatment with a PIM inhibitor, selective PI3Kδ inhibitor (eg, idelalisib), or a pan-PI3K inhibitor.
- Receipt of anticancer medications, therapies, or investigational drugs within protocol-defined intervals before the date of the first dose of study treatment.
- Current or previous other malignancy within 3 years of study entry, except cured (or treated with curative intent and no evidence of disease) basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
- History of liver function abnormality requiring investigation and/or treatment (eg, due to excessive alcohol or drug-induced liver injury).
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
- Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment, and exposure to a live vaccine within 30 days of study treatment administration.
- Known HIV infection.
- Evidence of HBV or HCV infection.
- History of stroke or intracranial hemorrhage within 6 months of the date of study treatment administration.
- History of clinically significant or uncontrolled cardiac disease.
- Presence of an abnormal ECG that is clinically meaningful. Screening QTc interval > 480 milliseconds is excluded (corrected by Fridericia).
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: INCB053914 + INCB050465
INCB053914 in combination with INCB050465.
|
Dose Escalation: INCB053914 at the protocol-defined starting dose in combination with INCB050465, with dose modifications based on tolerability criteria. Dose Expansion: Recommended dose from the dose-escalation study. Dose Escalation: INCB050465 at the protocol-defined starting dose in combination with INCB053914, with dose modifications based on tolerability criteria. Dose Expansion: Recommended dose from the dose-escalation study. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of treatment-emergent adverse events (TEAEs)
Time Frame: Up to approximately 6 months
|
TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
|
Up to approximately 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cmax of INCB053914 in combination with INCB050465
Time Frame: Day 15
|
Maximum observed plasma concentration.
|
Day 15
|
Tmax of INCB053914 in combination with INCB050465
Time Frame: Day 15
|
Time to maximum plasma concentration.
|
Day 15
|
Cmin of INCB053914 in combination with INCB050465
Time Frame: Day 15
|
Minimum observed plasma concentration during the dosing interval.
|
Day 15
|
AUC0-t of INCB053914 in combination with INCB050465
Time Frame: Day 15
|
Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.
|
Day 15
|
Cl/F of INCB053914 in combination with INCB050465
Time Frame: Day 15
|
Oral dose clearance.
|
Day 15
|
Overall response rate
Time Frame: Up to approximately 6 months
|
Defined as the percentage of participants with a complete remission (CR)/complete metabolic response (CMR) or partial remission (PR)/partial metabolic response (PMR) as defined by investigator assessment per revised Lugano classification criteria for lymphomas.
|
Up to approximately 6 months
|
Duration of response
Time Frame: Up to approximately 6 months
|
Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among participants who achieve an objective response, as determined by radiographic disease assessment.
|
Up to approximately 6 months
|
Progression-free survival
Time Frame: Up to approximately 6 months
|
Defined as the time from the date of the first dose of any study drug until the earliest date of disease progression, as determined by radiographic disease assessment, or death from any cause, whichever occurs first.
|
Up to approximately 6 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- INCB 53914-102
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Refractory Diffuse Large B-Cell Lymphoma
-
NeoImmuneTechRecruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Refractory High Grade B-Cell Lymphoma | Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-cell LymphomaUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingRecurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Recurrent Diffuse Large B-Cell... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNektar TherapeuticsRecruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Recurrent Grade 3b Follicular Lymphoma | Refractory Grade 3b Follicular... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterADC TherapeuticsWithdrawnRecurrent Diffuse Large B-Cell Lymphoma | Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Recurrent High... and other conditionsUnited States
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
David Bond, MDRecruitingRecurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Recurrent... and other conditionsUnited States
-
Nathan DenlingerBristol-Myers SquibbRecruitingB-Cell Non-Hodgkin Lymphoma-Recurrent | Diffuse Large B-Cell Lymphoma-Recurrent | Follicular Lymphoma-Recurrent | High Grade B-Cell Lymphoma-Recurrent | Primary Mediastinal Large B-Cell Lymphoma-Recurrent | Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent and other conditionsUnited States
-
University Hospital Southampton NHS Foundation...Hoffmann-La RocheTerminatedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited Kingdom
-
Dana-Farber Cancer InstituteBayer; AbbVieActive, not recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited States
-
The Lymphoma Academic Research OrganisationLymphoma Study AssociationNot yet recruitingRefractory High Grade B-Cell Lymphoma | Diffuse Large B-cell Lymphoma Refractory | Refractory Transformed B-cell Non-Hodgkin Lymphoma | Refractory Primary Mediastinal Large B-Cell LymphomaFrance
Clinical Trials on INCB053914
-
Medical College of WisconsinWithdrawnRefractory Multiple Myeloma | Relapse Multiple Myeloma
-
Incyte CorporationTerminated