Brief Title: A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose Escalation Part: Dose Limiting Toxicities (DLTs)

Primary Outcome 1 - Timeframe: DLTs will be assessed during the first cycle (21 days) in each cohort

Primary Outcome 2 - Measure: Adverse Events (AEs)

Primary Outcome 2 - Timeframe: AEs are collected throughout trial until the end of the safety follow-up period (30 days after last dose)

Primary Outcome 3 - Measure: Expansion Part: Evaluate anti-tumor activity

Primary Outcome 3 - Timeframe: Response assessment will be evaluated through trial completion, up to 5 years after last patient first visit.

Primary Outcome 4 - Measure: Safety Laboratory parameters (Hematology: Hematocrit, Hemoglobin Mean platelet volume, Platelet Count, Red Blood Cell Count, White Blood Cell Count) )

Primary Outcome 4 - Timeframe: Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)

Primary Outcome 5 - Measure: 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)

Primary Outcome 5 - Timeframe: Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)

Primary Outcome 6 - Measure: Safety Laboratory parameters (Coagulation: Prothrombin time, International normalized ratio, Activated partial thromboplastin time)

Primary Outcome 6 - Timeframe: Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)

Primary Outcome 7 - Measure: Safety Laboratory parameters (Urinalysis: Leukocytes, Protein)

Primary Outcome 7 - Timeframe: Safety Laboratory parameters are collected throughout trial until the end of the safety follow-up period (30 days after last dose)

CONDITION

• Dose Escalation Part: Locally Advanced or Metastatic Solid Tumor(s)
• Expansion Part: Prostate Cancer
• Expansion Part: Esophageal Cancer
• Expansion Part: Triple Negative Breast Cancer (TNBC)
• Expansion Part: Squamous Cell Carcinoma of Head and Neck (SCCHN)
• Expansion Part: Non-small Cell Lung Cancer (NSCLC)
• Expansion Part: Bladder Cancer
• Expansion Part: Uterine Cancer

ELIGIBILITY

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:
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.

- Must have measurable disease according to response assessment criteria relevant to the tumor type.

- Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1.

- 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):
Has an uncontrolled intercurrent illness, including but not limited to:
Ongoing or active infection requiring intravenous treatment with anti-infective therapy

- 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 significant autoimmune disease Subjects with a history of grade 3 or higher irAEs that led to treatment discontinuation.

- Subjects with a 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 GEN1044.

- Serious, non-healing wound, skin ulcer (of any grade), or bone fracture.

- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke.
Prior therapy:
Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 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 GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved.

- 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Roberto Oliveri, MD

Role: Study Director

Affiliation: Genmab

Overall Contact

Name: Roberto Oliveri, MD

Phone: +4570202728

Email: clinicaltrials@genmab.com

LOCATION