A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of the trial is to evaluate the safety, determine the recommended phase 2 dose, and assess preliminary clinical activity of GEN1044 in subjects with solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1/Phase 2 |
Detailed Description
The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose escalation part (phase 1) and an expansion part (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined from phase 1.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Open Label, single arm where GEN1044 will be administered |
Biological: GEN1044 is an IgG1 bispecific antibody targeting CD3 and 5T4.
GEN1044 will be administered (intravenously) in cycles of 21 days. The dose-levels will be determined by the starting dose and the escalation steps taken in the trial.
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Outcome Measures
Primary Outcome Measures
- Dose Escalation Part: Dose Limiting Toxicities (DLTs) [DLTs will be assessed during the first cycle (21 days) in each cohort]
To assess recommended phase 2 dose
- Adverse Events (AEs) [AEs are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
To assess the safety and tolerability of GEN1044 throughout the treatment period of patients participating in the trial
- Expansion Part: Evaluate anti-tumor activity [Response assessment will be evaluated through trial completion, up to 5 years after last patient first visit.]
Reduction in tumor size according to response assessment (Objective Response Rate)
- Safety Laboratory parameters (Hematology: Hematocrit, Hemoglobin Mean platelet volume, Platelet Count, Red Blood Cell Count, White Blood Cell Count) ) [Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
To assess the safety and tolerability of GEN1044 throughout the treatment period of patients participating in the trial
- Safety Laboratory parameters (Biochemistry: ALP, ALT, Amylase, AST, Bilirubin, BUN, Calcium, Chloride, Creatinine, CRP, Albumin, GGT, Glucose, Glycosylated hemoglobin, LDH, Lipase, Magnesium, Nitrogen, Phosphate, Potassium, Protein, Sodium, Uric acid) [Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
To assess the safety and tolerability of GEN1044 throughout the treatment period of patients participating in the trial
- Safety Laboratory parameters (Coagulation: Prothrombin time, International normalized ratio, Activated partial thromboplastin time) [Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
To assess the safety and tolerability of GEN1044 throughout the treatment period of patients participating in the trial
- Safety Laboratory parameters (Urinalysis: Leukocytes, Protein) [Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
To assess the safety and tolerability of GEN1044 throughout the treatment period of patients participating in the trial
Secondary Outcome Measures
- To establish the pharmacokinetic profile (PK) profile of GEN1044 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Rate at which the drug is removed from the body (clearance)
- To establish the PK profile of GEN1044 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Amount of drug in the body (volume of distribution)
- To establish the PK profile of GEN1044 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Area-under-the-concentration-time curve (AUC0-C last)
- To establish the PK profile of GEN1044 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Maximum concentration of GEN1044 (Cmax) after dosing
- To establish the PK profile of GEN1044 [Assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Time after dosing at which the maximum drug concentration was observed (Tmax)
- To establish the PK profile of GEN1044 [PK parameter will be assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Time after dosing at which the lowest drug concentration is observed before the next dose is administered (CTrough)
- To establish the PK profile of GEN1044 [PK parameter will be assed throughout trial until the end of the safety follow-up period (30 days after last dose)]
Elimination half-life of the drug (T1/2)
- Evaluate immunogenicity of GEN1044 [ADA are collected throughout trial until the end of the safety follow-up period (30 days after last dose)]
Anti-drug antibody response (ADA)
- Expansion Part: Evaluate efficacy [Assessment will be made through trial completion, up to 5 years after last patient first visit.]
Progression free survival (Overall survival)
Eligibility Criteria
Criteria
Key Inclusion Criteria:
Dose Escalation Part:
• Subject with locally advanced or metastatic solid tumor(s) (excluding subjects with primary central nervous system [CNS] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy.
Expansion Part:
• Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, Triple Negative Breast Cancer (TNBC), Squamous Cell Carcinoma of the Head and Neck (SCCHN), Non-small Cell Lung Cancer (both adenocarcinoma (ACC) and squamous cell carcinoma (SCC) (NSCLC/ACC and NSCLC/SCC), Bladder Cancer.
Both Parts:
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Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures.
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Must have measurable disease according to response assessment criteria relevant to the tumor type.
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Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.
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A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception.
Key Exclusion Criteria (both parts):
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Has an uncontrolled intercurrent illness, including but not limited to:
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Ongoing or active infection requiring intravenous treatment with anti-infective therapy
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Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia.
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Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management.
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Ongoing or recent evidence of significant autoimmune disease Subjects with a history of grade 3 or higher irAEs that led to treatment discontinuation.
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Subjects with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
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History of chronic liver disease or evidence of hepatic cirrhosis.
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History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis.
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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 GEN1044.
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Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.
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Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
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Prior therapy:
Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed.
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Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.
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Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or has known allergies, hypersensitivity, or intolerance to GEN1044 or its excipients.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tennesse Oncology, PLLC - Nashville | Nashville | Tennessee | United States | 37203 |
| 2 | MD Anderson Cancer center | Houston | Texas | United States | 77054 |
| 3 | Rigshospitalet (Copenhagen University Hospital) | Copenhagen | Denmark | 2100 | |
| 4 | Chaim Sheba Medical Center | Ramat Gan | Israel | 5265601 | |
| 5 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | 8035 | |
| 6 | Fundacion Jimenez Diaz | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Genmab
- AbbVie
Investigators
- Study Director: Roberto Oliveri, MD, Genmab
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GCT1044-01
- 2019-003998-26