Clinical trial NCT03688152: A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Keywords: Diffuse large B-cell lymphoma
DLBCL
Non-Hodgkin lymphoma
phosphatidylinositol 3-kinase delta inhibitor
PI3Kδ
PIM kinases
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-09-28
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of INCB053914 in combination with INCB050465 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Cmax of INCB053914 in combination with INCB050465
timeFrame: Day 15
measure: Tmax of INCB053914 in combination with INCB050465
timeFrame: Day 15
measure: Cmin of INCB053914 in combination with INCB050465
timeFrame: Day 15
measure: AUC0-t of INCB053914 in combination with INCB050465
timeFrame: Day 15
measure: Cl/F of INCB053914 in combination with INCB050465
timeFrame: Day 15
measure: Overall response rate
timeFrame: Up to approximately 6 months
measure: Duration of response
timeFrame: Up to approximately 6 months
measure: Progression-free survival
timeFrame: Up to approximately 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Santa Monica
country: United States
facility: UCLA Healthcare Hematology-Oncology
state: California
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
Study officials:
affiliation: Incyte Corporation
name: Fred Zheng, MD
role: STUDY_DIRECTOR
References: