GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors
- Conditions
- Gastric CancerUrothelial CancerColorectal CancerNon-small Cell Lung CancerRenal Cell CarcinomaPancreatic CancerTriple Negative Breast Cancer
- Interventions
- Biological: GEN1029 (HexaBody®-DR5/DR5)
- Registration Number
- NCT03576131
- Lead Sponsor
- Genmab
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GEN1029 (HexaBody®-DR5/DR5) GEN1029 (HexaBody®-DR5/DR5) -
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) From Day 1 to 28 days after the first dose of study drug 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 >= Grade 3 Laboratory Results Day 1 through Day 565 (corresponding to maximum observed duration) 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Day 1 through Day 565 (corresponding to maximum observed duration) 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.
- Secondary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The Cmax 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 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The Vss of Hx-DR5-01 and Hx-DR5-05 are reported.
Duration of Response (DoR) According to RECIST 1.1 From Day 1 through 8.8 months (corresponding to maximum observed duration) 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.
Plasma Concentration of Hx-DR5-01 and Hx-DR5-05 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The plasma concentration 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 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The AUC(0-Clast) of Hx-DR5-01 and Hx-DR5-05 are reported.
Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage From Baseline (Day 1) through 8.8 months (corresponding to maximum observed duration) 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.
Progression-Free Survival (PFS) According to RECIST 1.1 From Day 1 through 8.8 months (corresponding to maximum observed duration) 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.
Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The AUC(0-inf) of Hx-DR5-01 and Hx-DR5-05 are reported.
Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The CL 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 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The Tmax of Hx-DR5-01 and Hx-DR5-05 are reported.
Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029 From Screening (Day -21 to -1) through Day 478 (corresponding to maximum observed duration) 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.
Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 From Day 1 through 8.8 months (corresponding to maximum observed duration) 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.
Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05 Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3 The t1/2 of Hx-DR5-01 and Hx-DR5-05 are reported.
Time to Response (TTR) According to RECIST 1.1 From Day 1 through 8.8 months (corresponding to maximum observed duration) 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.
Overall Survival (OS) According to RECIST 1.1 From Day 1 through 8.8 months (corresponding to maximum observed duration) 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.
Trial Locations
- Locations (6)
UT M.D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Hospital Univeritario Vall d'Hebron
🇪🇸Barcelona, Spain
The Royal Mardsen NHS Foundation Trust
🇬🇧Sutton, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust
🇬🇧Newcastle, United Kingdom
START Madrid CIOCC
🇪🇸Madrid, Spain