Clinical trial NCT02431260: An Open-Label, Dose-Escalation Study of INCB054329 in Patients With Advanced Malignancies
Official title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054329 in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors and Hematologic Malignancy
Keywords: solid tumor
lymphoma
BET bromodomain inhibitor
BRD
Diffuse large B-cell lymphoma (DLBCL)
Burkitt's lymphoma
c-MYC
colorectal cancer
Non-small cell lung cancer
Pancreatic adenocarcinoma
castration-resistant prostate cancer
breast cancer
NUT midline carcinoma
leukemia
acute myeloid leukemia (AML)
myelodysplastic syndrome (MDS)
myeloproliferative neoplasms
myelofibrosis (MF)
multiple myeloma (MM)
MDS/MPN
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2015-04-30
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This was a study of INCB054329 given to patients with advanced malignancies that were conducted in three treatment groups. Each treatment group had a dose escalation (Part 1) and a dose expansion (Part 3), two of the treatment groups also had an intra-patient dose titration (Part 2).


Eligibility criteria: Key Inclusion Criteria:

* Confirmed diagnosis of advanced malignancy:

  * Treatment Group A (TGA): Part 1 and Part 2: Any advanced solid tumor or lymphoma; Part 3: Histologically confirmed disease in specific solid tumors and lymphomas
  * Treatment Group B (TGB): Acute Leukemia (Part 3 - acute myeloid leukemia \[AML\] only), myelodysplastic syndrome (MDS), myelodysplastic /myeloproliferative neoplasms (MDS/MPN) and myelofibrosis (MF)
  * Treatment Group C (TGC): Multiple myeloma
* Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 in Parts 1 and 2 dose escalation and titration, and 0, 1, 2 in Part 3 dose expansion

Key Exclusion Criteria:

* Inadequate hematopoietic, liver, endocrine or renal function
* Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:

  * \< 6 weeks for mitomycin-C or nitrosoureas
  * \< 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication)
  * \< 28 days for any antibodies or biological therapies
  * \< 5 half-lives for all other anticancer medications, or sponsor approval
* Prior radiotherapy within 2 weeks prior to first dose of study drug
* Untreated brain or central nervous system (CNS) metastases
* Type 1 diabetes or uncontrolled Type 2 diabetes
* Any sign of clinically significant bleeding

Primary outcomes:
measure: Number of Participants With a Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 30 days
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) Analysis of INCB054329
timeFrame: Summary of steady-state PK parameters by dosing regimen at Day 15
measure: Time to Maximum Plasma Concentration (Tmax) Analysis of INCB054329
timeFrame: Summary of steady-state PK parameters by dosing regimen at Day 15
measure: Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) Analysis of INCB054329
timeFrame: Summary of steady-state PK parameters by dosing regimen at Day 15
measure: AUC0-t Analysis of INCB054329
timeFrame: Summary of steady-state PK parameters by dosing regimen at Day 15
measure: Cl/F Analysis of INCB054329
timeFrame: Summary of steady-state PK parameters by dosing regimen at Day 15
measure: Pharmacodynamics (PD) Analysis - Total c-Myc % Inhibition Versus INCB054329
timeFrame: Day 15 in all cohorts
measure: Objective Response Rate (ORR)
timeFrame: Baseline through end of study, up to 6 months
measure: Duration of Response (DOR)
timeFrame: Baseline through end of study, up to 6 months
measure: Progression Free Survival (PFS)
timeFrame: Baseline through end of study, up to 6 months
measure: Overall Survival (OS)
timeFrame: Baseline through end of study, up to 6 months for participants in Part 2
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, Medical Center at Mount Zion
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute Research Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Incyte Corporation
name: Fred Zheng, M.D.
role: STUDY_DIRECTOR
References:
citation: Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.