First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of GEN1029 in patients with malignant solid tumors
- Conditions
- Malignant solid tumors: Patients with advanced and/or metastatic colorectal cancer (CRC), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), renal cell carcinoma (RCC), gastric (incl. esophagogastric junction) cancer, pancreatic cancer or urothelial cancer.MedDRA version: 20.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001394-16-ES
- Lead Sponsor
- Genmab B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 206
- 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 the last infusion of IMP
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 156
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
- Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first IMP 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
- Have received a cumulative dose of corticosteroid = 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first IMP 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 IMP administration
- Any prior therapy with a compound targeting DR4 or DR5
- History of chronic liver disease or evidence of hepatic cirrhosis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: - Determine the MTD and/or the recommended Phase 2 dose(s) (RP2D)<br> - Establish the safety profile of GEN1029<br> ;<br> Secondary Objective: - Establish the PK profile and evaluate immunogenicity of GEN1029 after single and multiple infusions<br> - Evaluate the anti-tumor activity of GEN1029<br> ;<br> Primary end point(s): - Dose limiting Toxicities (DLTs)<br> - Adverse events (AEs) and safety laboratory parameters (hematology and biochemistry)<br> ;<br> Timepoint(s) of evaluation of this end point: DLTs: dose limiting toxicities will be collected for the first two cycles i.e. DLT period of 28 days.<br> AEs: screening; Day 1, 2, 8 during Cycles 1-3; Days 1, 8 during subsequent Cycles (4-PD); EoT; 4, 13, 26, 39, 52 Weeks after last dosing.<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): - PK parameters of GEN1029<br> - Immunogenicity of GEN1029<br> - Anti-tumor activity measured by tumor shrinkage<br> - Objective Response, Progression-Free Survival (PFS), Overall Survival<br> (OS) and Duration of Response (DoR)<br> ;Timepoint(s) of evaluation of this end point: During the entire study