First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors
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Study Summary
To evaluate the safety of GEN1046 in patients with malignant solid tumors
To determine the maximum tolerated dose (DMT) or the recommended dose for phase II (DRFII)
To determine the security profile of GEN1046
To evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
To find the best dose and study the effects (good and bad) of the experimental immunotherapy GEN1046.
To evaluate the safety and pharmacokinetics of GEN1046 in Japanese patients with malignant solid tumors.
The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together with standard of care treatment (docetaxel) or another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of patients with certain types of cancer. All subjects will receive active drug; no one will receive placebo.
- For Dose Escalation: • 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: • 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 For separate expansion cohorts: metastatic NSCLC without prior systemic treatment regimens for metastatic disease. For Both Dose Escalation and Expansion Have measurable disease according to RECIST 1.1 Have Eastern Cooperative Oncology Group (ECOG) 0-1 Have an acceptable hematological status Have acceptable liver function Have an acceptable coagulation status Have acceptable renal function - Should provide a tumor tissue sample (formalin-fixed paraffin-embedded [FFPE] blocks/slides) from archival tissue or fresh biopsy collected before C1D1, preferably derived from advanced disease stage.
- Have uncontrolled intercurrent illness, including but not limited to:
- Ongoing or active infection requiring intravenous treatment with anti-infective therapy, or any ongoing systemic inflammatory condition requiring further diagnostic work-up or management during screening.
- 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 evidence of autoimmune disease
- History of irAEs that led to prior checkpoint treatment discontinuation
- Prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade
- 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 acasunlimab
- 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 within 14 days prior to first dose of acasunlimab. Note: 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 acasunlimab administration. Accepted exceptions are bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab
- Toxicities from previous anti-cancer therapies that have not adequately resolved
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Clinical Study Information for Healthcare Providers
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