Clinical trial NCT03576131: GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors
Official title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1029 in Patients With Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Non-small Cell Lung Cancer
Triple Negative Breast Cancer
Renal Cell Carcinoma
Gastric Cancer
Pancreatic Cancer
Urothelial Cancer
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: From Day 1 to 28 days after the first dose of study drug
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through Day 565 (corresponding to maximum observed duration)
measure: Number of Participants With >= Grade 3 Laboratory Results
timeFrame: Day 1 through Day 565 (corresponding to maximum observed duration)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Plasma Concentration of Hx-DR5-01 and Hx-DR5-05
timeFrame: Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3
measure: Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029
timeFrame: From Screening (Day -21 to -1) through Day 478 (corresponding to maximum observed duration)
measure: Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage
timeFrame: From Baseline (Day 1) through 8.8 months (corresponding to maximum observed duration)
measure: Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
measure: Progression-Free Survival (PFS) According to RECIST 1.1
timeFrame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
measure: Overall Survival (OS) According to RECIST 1.1
timeFrame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
measure: Duration of Response (DoR) According to RECIST 1.1
timeFrame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
measure: Time to Response (TTR) According to RECIST 1.1
timeFrame: From Day 1 through 8.8 months (corresponding to maximum observed duration)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Houston
country: United States
facility: UT M.D Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Hospital Univeritario Vall d'Hebron
city: Madrid
country: Spain
facility: START Madrid CIOCC
city: Newcastle
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Mardsen NHS Foundation Trust
Study officials:
affiliation: Newcastle Hospitals NHS Foundation Trust
name: Ruth Plummer, Professor
role: PRINCIPAL_INVESTIGATOR
References: