Malignant solid tumors: Patients with relapsed or refractory, advanced and/or metastatic melanoma, Non-Small Cell Lung Cancer (NSCLC) or Colorectal Cancer (CRC) who are not anymore candidates for standard therapy MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: DuoBody- CD40x4-1BB
Product Code: GEN1042
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: GEN1042 (DuoBody-CD40x4-1BB)
CAS Number: 2253891-70-0
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 adequate organ and bone marrow function as defined in protocol. 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 melanoma, NSCLC, CRC cancer for whom there are no alternative treatment options. 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 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: •Subject has uncontrolled intercurrent illness, including but not limited to: • Ongoing or active infection requiring intravenous treatment with antiinfective 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. • 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. • History of liver disease (e.g., alcoholic hepatitis or non-alcoholic steatohepatitis (NASH), drug-related or auto-immune hepatitis. • 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 GEN1042. • 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 GEN1042 administration. Palliative radiotherapy will be allowed. • Unless otherwise noted, treatment with an anti-cancer agent (within 21 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1042 administration. The use of RANK-L inhibitors and bisphosphonates (if on a stable dose for at least 4 weeks) is permitted while participating in this trial. However, the initiation of growth factors and bisphosphonates is not allowed during the first 4 weeks of GEN1042 treatment, unless agreed upon by the investigator and medical monitor. • 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 maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) - Establish the safety profile of GEN1042;Secondary Objective: - Establish the PK profile of GEN1042 - Evaluate immunogenicity of GEN1042 - Evaluate the anti-tumor activity of GEN1042;Primary end point(s): - Dose-limiting toxicity (DLT) - Adverse events (AEs) and safety laboratory parameters;Timepoint(s) of evaluation of this end point: DLTs: dose limiting toxicities will be collected for the first cycle i.e. DLT period of 3 weeks (21 days). AEs: screening; Day 1, 2, 3, 8, 15 during Cycles 1-2; Days 1, 8, 15 during Cycles 3-6, Day 1 subsequent Cycles (7-PD); EoT; 4, 8, 12, subsequent every 12 (survival follow-up) Weeks after last dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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
Denmark, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Genmab A/S
Outcome results
None listed