First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors

The trial is an open-label, multi-center safety trial of GEN1046. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) 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.

Inclusion Criteria:

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 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

Exclusion Criteria:

• Have uncontrolled intercurrent illness, including but not limited to:
  • Ongoing or active infection requiring intravenous treatment with antiinfective 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 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 GEN1046
  • 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: 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
• Toxicities from previous anti-cancer therapies that have not adequately resolved