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 or refuse standard therapy MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: DuoBody-PD-L1x4-1BB
Product Code: GEN1046
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: GEN1046 (DuoBody-PD-L1x4-1BB)
CAS Number: 2253937-12-9
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Dose Escalation: • Measurable disease according to RECIST 1.1. • Eastern Cooperative Oncology Group (ECOG) 0-1. • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. • 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 Dose Expansion: • Measurable disease according to RECIST 1.1. • Eastern Cooperative Oncology Group (ECOG) 0-1. • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol. • 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 or refuse 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 285 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: •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 prior immunotherapy treatment 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 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. • Subjects who discontinued treatment due to disease progression within the first 6 weeks of a CPI containing treatment. • Prior treatment with a 4-1BB (CD137) targeted agent. • Prior treatment with a T-cell agonist or anti-CTLA-4 targeted agent within 12 weeks prior to the initiation of treatment. • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Determine the MTD and/or the recommended Phase 2 dose (RP2D) - Establish the safety profile of GEN1046;Secondary Objective: - Establish the PK profile - Evaluate immunogenicity of GEN1046 - Evaluate the anti-tumor activity of GEN1046;Primary end point(s): Dose Escalation: - Dose limiting Toxicities (DLTs) - Adverse events (AEs) and safety laboratory parameters Dose Expansion: - Adverse events (AEs) and safety laboratory parameters ;Timepoint(s) of evaluation of this end point: Dose Escalation: - DLTs: dose limiting toxicities will be collected for the first two cycles i.e. DLT period of 42 days. - 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. Dose Expansion: - 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation: - PK parameters - Anti-Drug Antibody (ADA) response - Anti-tumor activity, i.e., reduction in tumor size according to RECIST 1.1: - Objective Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR) Dose Expansion: - PK parameters - Anti-Drug Antibody (ADA) response - Anti-tumor activity, i.e., reduction in tumor size according to RECIST 1.1: - Objective Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR) ;Timepoint(s) of evaluation of this end point: During the entire study | — |
Countries
Czech Republic, Hungary, Israel, Italy, Poland, Spain, United States
Contacts
Public ContactClinical Trial Information
Genmab A/S
Outcome results
None listed