GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors
Study Details
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
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
The trial is an open-label, multi-center safety 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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: GEN1029 (HexaBody®-DR5/DR5) Open label, single arm trial where GEN1029 will be administered |
Biological: GEN1029 (HexaBody®-DR5/DR5)
GEN1029 will be administered intravenously once every 14 days. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.
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Outcome Measures
Primary Outcome Measures
- Dose Limiting Toxicities (DLTs) [DLTs will be identified from the two first treatment cycles (28 days, a cycle is 14 days)]
To determine recommended phase 2a dose of GEN1029
- Adverse events (AEs) [Throughout and at the end of trial (up to 24 months after first treatment cycle (a treatment cycle is 14 days))]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Secondary Outcome Measures
- Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Area under the plasma concentration-time curve from time zero to infinity (AUC) of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Area under the plasma concentration-time curve from time 0 to day 14 (AUC 0-->14days) of GEN1029 [Treatment cycle 2 and 3 i.e. up to 28 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Time to reach maximum plasma concentration (Tmax) of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Terminal elimination half-life (T1/2) of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Area under the plasma concentration-time curve from time zero to last concentration. [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- PK: Volume of distribution of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- Plasma clearance of GEN1029 [First 3 treatment cycles i.e. up to 42 days (each cycle is 14 days)]
Plasma concentrations of GEN1029
- Percentage of participants with GEN1029 anti-drug antibodies [From day one through up to 70 days after the last dose of study drug (up to 36 months)]
Percentage of participants with treatment-emergent positive anti-GEN1029 antibodies by treatment group
- Anti-tumor activity measured by tumor shrinkage (based on computerized tomography evaluations [From day 1 until disease progression as assessed by the investigator, the start of new anticancer therapy, withdrawal of consent, or death, whichever occurs first (up to 36 months)]
Anti-tumor activity
- Objective response rate (ORR) [From day 1 until disease progression as assessed by the investigator, the start of new anticancer therapy, withdrawal of consent, or death, whichever occurs first (up to 36 months)]
Proportion of patients who have achieved a partial response (PR) or complete response (CR) according to RECIST 1.1.
- Progression-free survival (PFS) [From day 1 until disease progression as assessed by the investigator, the start of new anticancer therapy, withdrawal of consent, or death, whichever occurs first (up to 36 months)]
PFS is defined as the time from date of first dose to objectively documented progression of disease or death
- Duration of response (DOR) [From day 1 until disease progression as assessed by the investigator, the start of new anticancer therapy, withdrawal of consent, or death, whichever occurs first (up to 36 months)]
DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death
- Overall survival (OS) [From day 1 until death or withdrawal from the study, whichever occurred first (up to 36 months)]
DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death
- Time to response (TTR) [From day 1 until disease progression as assessed by the investigator, the start of new anticancer therapy, withdrawal of consent, or death, whichever occurs first (up to 36 months)]
TTR is defined as the number of days from first dose to the first partial or complete response
Eligibility Criteria
Criteria
Inclusion Criteria (main):
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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.
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Patient must be ≥ 18 years of age
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Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
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Have an acceptable hematological status
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Have an acceptable renal function
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Have an acceptable liver function
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Have an Eastern Cooperative Oncology Group performance status of 0 or 1
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Body weight ≥ 40kg
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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):
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Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first GEN1029 administration
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Have clinically significant cardiac disease
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Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management
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Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke
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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)
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Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first GEN1029 administration
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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
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Radiotherapy within 14 days prior to first GEN1029 administration
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Any prior therapy with a compound targeting DR4 or DR5
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History of chronic liver disease or evidence of hepatic cirrhosis
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Yale University | New Haven | Connecticut | United States | 06510 |
2 | UT M.D Anderson Cancer Center | Houston | Texas | United States | 77030 |
3 | Hospital Univeritario Vall d'Hebron | Barcelona | Spain | ||
4 | START Madrid CIOCC | Madrid | Spain | ||
5 | The Newcastle upon Tyne Hospitals NHS Foundation Trust | Newcastle | United Kingdom | ||
6 | The Royal Mardsen NHS Foundation Trust | Sutton | United Kingdom |
Sponsors and Collaborators
- Genmab
Investigators
- Principal Investigator: Ruth Plummer, Professor, Newcastle Hospitals NHS Foundation Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GCT1029-01