Clinical trial NCT03538028: A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies
Official title: A Phase 1 Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN02385 in Participants With Select Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Microsatellite Instability (MSI)-High Endometrial Cancer
Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ])
Esophageal Cancer
Hepatocellular Carcinoma
Melanoma (Uveal Melanoma Excluded)
Merkel Cell Carcinoma
Mesothelioma
MSI-high Colorectal Cancer
Non-small Cell Lung Cancer (NSCLC)
Ovarian Cancer
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Small Cell Lung Cancer (SCLC)
Renal Cell Carcinoma (RCC)
Triple-negative Breast Cancer
Urothelial Carcinoma
Diffuse Large B-cell Lymphoma
Keywords: lymphocyte activation gene (LAG)
LAG-3
advanced solid tumor
metastatic solid tumor
relapsed/refractory DLCBL
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-05-25
Enrollment: 22
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 determine the safety, tolerability, and preliminary efficacy of INCAGN02385 in participants with advanced malignancies.


Eligibility criteria: Inclusion Criteria:

* Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
* Disease progression after treatment with available therapies that are known to confer clinical benefit, or intolerant to treatment, or refuse noncurative standard treatment. There is no limit to the number of prior treatment regimens.
* Participants with advanced or metastatic cervical cancer, MSI-high endometrial cancer, gastric cancer (including stomach and GEJ), esophageal cancer, hepatocellular carcinoma, melanoma (uveal melanoma excluded), Merkel cell carcinoma, mesothelioma, MSI-high colorectal cancer, NSCLC, ovarian cancer, SCCHN, SCLC, RCC, triple-negative breast cancer, and urothelial carcinoma, or alternative immunogenic tumor types with medical monitor approval. Participants with DLBCL may participate in Part 2 of the study.
* Presence of measureable disease based on RECIST v1.1 for solid tumors or the Lugano classification for DLBCL.
* Willingness and ability to safely undergo pretreatment and on-treatment tumor biopsies.
* Eastern Cooperative Oncology Group performance status 0 or 1.

Exclusion Criteria:

* Laboratory and medical history parameters outside the protocol-defined range.
* Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
* Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
* Receipt of a live vaccine within 30 days of planned start of study drug.
* Active autoimmune disease that required systemic treatment in the past.
* Known active CNS metastases and/or carcinomatous meningitis.
* Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. See protocol-defined exceptions.
* Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
* Active infection requiring systemic therapy.
* Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
* Known history of HIV (HIV 1/2 antibodies).
* Prior treatment with an anti-LAG-3 antibody for any indication.

Primary outcomes:
measure: Number of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Cmax of INCAGN02385
timeFrame: Up to 12 months
measure: Tmax of INCAGN02385
timeFrame: Up to 12 months
measure: Cmin of INCAGN02385
timeFrame: Up to 12 months
measure: AUC0-t of INCAGN02385
timeFrame: Up to 12 months
measure: Objective response rate (ORR) in participants with advanced or metastatic solid tumors
timeFrame: Up to 12 months
measure: Disease control rate (DCR) in participants with advanced or metastatic solid tumors
timeFrame: Up to 12 months
measure: Duration of response (DOR) in participants with advanced or metastatic solid tumors
timeFrame: Up to 12 months
measure: Progression-free survival (PFS) in participants with advanced or metastatic solid tumors
timeFrame: Up to 12 months
measure: ORR in participants with diffuse large B-cell lymphoma (DLBCL)
timeFrame: Up to 12 months
measure: DOR in participants with DLBCL
timeFrame: Up to 12 months
measure: PFS in participants with DLBCL
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Center
state: California
city: Hackensack
country: United States
facility: Hackensack Medical Center
state: New Jersey
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Incyte Corporation
name: John Janik, MD
role: STUDY_DIRECTOR
References: