GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors

Phase 2TerminatedNCT03576131

Genmab48 enrolled

Overview

The purpose of the trial is to evaluate the safety of GEN1029 (HexaBody®-DR5/DR5) in a mixed population of patients with specified solid tumors

The trial is an open-label, multi-center first-in-human trial of GEN1029 (HexaBody®-DR5/DR5). The trial consists of two parts a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Colorectal Cancer Non-small Cell Lung Cancer Triple Negative Breast Cancer Renal Cell Carcinoma Gastric Cancer Pancreatic Cancer Urothelial Cancer

Interventions

GEN1029 (HexaBody®-DR5/DR5)BIOLOGICAL

GEN1029 will be administered intravenously. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria (main): * Patients with advanced and/or metastatic cancer who have no available standard therapy or who are not candidates for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1029 may be beneficial. * Patient must be ≥ 18 years of age * Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 * Have an acceptable hematological status * Have an acceptable renal function * Have an acceptable liver function * Have an Eastern Cooperative Oncology Group performance status of 0 or 1 * Body weight ≥ 40kg * Patients both females and males, of childbearing or reproductive potential must agree to use adequate contraception from screening visit until six months after last infusion of GEN1029 Exclusion Criteria (main): * Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first GEN1029 administration * Have clinically significant cardiac disease * Have uncontrolled hypertension as defined in the protocol * Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke * History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of Investigational Medicinal Product (IMP) * Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first GEN1029 administration * History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial * Radiotherapy within 14 days prior to first GEN1029 administration * Any prior therapy with a compound targeting DR4 or DR5 * History of chronic liver disease or evidence of hepatic cirrhosis

Locations (6)

Yale University

New Haven, Connecticut, United States

UT M.D Anderson Cancer Center

Houston, Texas, United States

Hospital Univeritario Vall d'Hebron

Barcelona, Spain

START Madrid CIOCC

Madrid, Spain

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

DLT criteria in the dose escalation phase of this trial are defined as hematologic toxicity including Grade (G) 4 neutropenia/thrombocytopenia for minimal duration of 7 days, G3/4 febrile neutropenia, \>=G3 thrombocytopenia with bleeding, or G4 anemia; and non-hematologic toxicity including G4 infusion-related reactions (IRR) or anaphylaxis, G3 IRR did not resolve to =\<G1 within 24 hours, \>=G3 diarrhea/vomiting (did not respond to optimal treatment within 2 days), G3 nausea (did not respond to optimal treatment within 7days), or Hy's law or protocol-specified toxicities related to liver function test results or amylase and/or lipase elevations; or any \>=G3 possibly related non-hematological AE, which occurred during first 2 cycles (as specified in protocol).

Time frame: From Day 1 to 28 days after the first dose of study drug

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically important'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening during the treatment period including the safety follow-up period.

Time frame: Day 1 through Day 565 (corresponding to maximum observed duration)

Number of Participants With >= Grade 3 Laboratory Results

Number of participants with laboratory measurements of Grade \>= 3 by NCI-CTCAE v4.03 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used.

Data from ClinicalTrials.gov

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