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

Primary Purpose

Colorectal Cancer, Non-small Cell Lung Cancer, Triple Negative Breast Cancer

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

GEN1029 (HexaBody®-DR5/DR5)

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management
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

Sites / Locations

Yale University
UT M.D Anderson Cancer Center
Hospital Univeritario Vall d'Hebron
START Madrid CIOCC
The Newcastle upon Tyne Hospitals NHS Foundation Trust
The Royal Mardsen NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GEN1029 (HexaBody®-DR5/DR5)

Arm Description

Outcomes

Primary Outcome Measures

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).

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.

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.

Secondary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05

The Cmax of Hx-DR5-01 and Hx-DR5-05 are reported.

Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05

The AUC(0-inf) of Hx-DR5-01 and Hx-DR5-05 are reported.

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

The AUC(0-Clast) of Hx-DR5-01 and Hx-DR5-05 are reported.

Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05

The CL of Hx-DR5-01 and Hx-DR5-05 are reported.

Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05

The Vss of Hx-DR5-01 and Hx-DR5-05 are reported.

Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05

The t1/2 of Hx-DR5-01 and Hx-DR5-05 are reported.

Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05

The Tmax of Hx-DR5-01 and Hx-DR5-05 are reported.

Plasma Concentration of Hx-DR5-01 and Hx-DR5-05

The plasma concentration of Hx-DR5-01 and Hx-DR5-05 are reported.

Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029

From positive ADA samples titer values and neutralizing antibody scores (positive or negative) were determined and reported. A participant was considered positive if negative at baseline (screening) and had at least one positive post-baseline result, or positive at baseline and had at least one positive post-baseline result with a titer higher than baseline. Number of participants with ADA positive to GEN1029 are reported.

Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage

Anti-tumor activity measured by tumor shrinkage was evaluated on based on of sum of the diameter(s) of all target lesions from the computerized tomography (CT) scan/positron emission tomography (PET)-CT scan. Largest tumor shrinkage is reported.

Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

The radiological evaluation was based on RECIST v1.1 using CT scan/PET-CT scan. The OR was defined as complete response (CR) or partial response (PR) per RECIST v1.1. The CR was defined as disappearance of all target and non-target lesions and reduction in short axis to <10 mm of any pathological and non-pathological lymph nodes. The PR was defined as >=30% decrease in sum of diameters of target lesions (compared to baseline), no unequivocal progression of existing non-target lesions, and no new lesion.

Progression-Free Survival (PFS) According to RECIST 1.1

The PFS was defined as the number of days from the date of first study drug administration to first progressive disease (PD) or death from any cause. The PD was defined as at least 20% (and >= 5 mm) increase in the sum of the longest diameter (LD) of target lesions, compared to the smallest sum of the target LDs recorded while in trial or the appearance of 1 or more new lesions; unequivocal progression of existing non-target lesions; and/or new lesion. The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET scan. The PFS was estimated using Kaplan-Meier method.

Overall Survival (OS) According to RECIST 1.1

Overall survival was defined as the number of days from date of first study drug administration to death due to any cause. If a subject was not known to have died, then OS was censored, and the censoring date was the latest date the subject was known to be alive (on or before the cut-off date). The OS was estimated using Kaplan-Meier method.

Duration of Response (DoR) According to RECIST 1.1

The radiological evaluation based on RECIST v1.1 was assessed using CT scan/PET-CT scan. The DoR was defined as duration from the first documentation of confirmed OR (CR or PR) to date of first progressive disease (PD) or death.

Time to Response (TTR) According to RECIST 1.1

TTR is defined as the number of days from first dose of study drug to the first documented confirmed CR or PR, which must be subsequently confirmed.

Full Information

NCT ID

NCT03576131

First Posted

May 8, 2018

Last Updated

July 31, 2023

Sponsor

Genmab

1. Study Identification

Unique Protocol Identification Number

NCT03576131

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decision

Study Start Date

April 30, 2018 (Actual)

Primary Completion Date

October 12, 2021 (Actual)

Study Completion Date

October 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genmab

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GEN1029 (HexaBody®-DR5/DR5)

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

GEN1029 (HexaBody®-DR5/DR5)

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Dose Limiting Toxicities (DLTs)

Description

Time Frame

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

Title

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

Description

Time Frame

Day 1 through Day 565 (corresponding to maximum observed duration)

Title

Number of Participants With >= Grade 3 Laboratory Results

Description

Time Frame

Day 1 through Day 565 (corresponding to maximum observed duration)

Secondary Outcome Measure Information:

Title

Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05

Description

The Cmax of Hx-DR5-01 and Hx-DR5-05 are reported.

Time Frame