GEN1046 Safety Trial in Patients With Malignant Solid Tumors
- Conditions
- Malignant solid tumors: Patients with relapsed or refractory, advanced and/or metastatic non-small cell lung cancer (NSCLC), endometrial carcinoma (EC), urothelial carcinoma (UC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), or cervical cancer who are not anymore candidates for standard therapyMedDRA version: 20.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003402-63-ES
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 192
For Both Dose Escalation and Expansion
• Subject must have measurable disease according to RECIST 1.1.
• Subject must have Eastern Cooperative Oncology Group (ECOG) 0-1.
• Subject must have organ and bone marrow function as follows:
• Bone marrow / hematological function:
- absolute neutrophil count (ANC) = 1.5 x 10(9)/L
- hemoglobin = 9.0 g/dL
- platelet count = 100 x 10(9)/L
• Liver function:
- Total bilirubin = ULN
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 1.5 x ULN
- Albumin = 30 g/L
• Coagulation status:
- prothrombin time (PT)/International normalized ratio (INR) = 1.5
- Activated partial thromboplastin time (aPTT) = 1.5 x ULN
• Renal function:
Glomerular filtration rate (GFR) = 45 mL/min/1.73 m²
For Dose Escalation:
• Subjects must have a histologically or cytologically confirmed non-CNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy.
For Expansion:
• Subjects must have histologically or cytological confirmed diagnosis of relapsed or refractory, advanced and/or metastatic NSCLC, EC, UC, TNBC, SCCHN, or cervical cancer who are not anymore candidates for standard therapy.
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 144
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48
•Subject has uncontrolled intercurrent illness, including but not limited to:
• Ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered less than 2 weeks prior to first dose
• Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
• Uncontrolled hypertension defined as systolic blood pressure = 160 mmHg and/or diastolic blood pressure = 100 mmHg, despite optimal medical management.
• Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs).
• Subjects with a history of grade 3 or higher irAEs that led to treatment discontinuation of a checkpoint inhibitor should be excluded. Subjects with irAEs below grade 3 that led to discontinuation should be discussed with the sponsor.
• Subjects with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade are excluded.
• History of chronic liver disease or evidence of hepatic cirrhosis.
• History of non-infectious pneumonitis that has required steroids or currently has pneumonitis.
• 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 GEN1046.
• Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
• Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke.
• Prior therapy:
• Radiotherapy: Radiotherapy within 14 days prior to first GEN1046 administration. Palliative radiotherapy will be allowed.
• Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1046 administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab.
• Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to grade 1 or less with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must have recovered to = grade 2.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Primary end point(s): - Dose limiting Toxicities (DLTs)<br> - Adverse events (AEs) and safety laboratory parameters<br> ;<br> Main Objective: - Determine the MTD and/or the recommended Phase 2 dose (RP2D)<br> - Establish the safety profile of GEN1046<br> ;<br> Secondary Objective: - Establish the PK profile<br> - Evaluate immunogenicity of GEN1046<br> - Evaluate the anti-tumor activity of GEN1046<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 42 days.<br> AEs: screening; Day 1, 2, 3, 8, 15 during Cycles 1-2; Days 1, 8, 15 during Cycle 3-4, Day 1 subsequent Cycles (5-PD); EoT; 4, 8, 12, subsequent every 12 (survival follow-up) Weeks after last dosing.<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): - PK parameters<br> - Anti-Drug Antibody (ADA) response<br> - Anti-tumor activity, i.e., reduction in tumor size according to RECIST 1.1:<br> - Objective Response Rate (ORR)<br> - Disease Control Rate (DCR)<br> - Duration of Response (DoR)<br> ;Timepoint(s) of evaluation of this end point: During the entire study