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


  • Org Study ID: GCT1046-01
  • Secondary ID: 2018-003402-63
  • NTC ID: NCT03917381
  • Sponsor: Genmab


The purpose of the trial is to evaluate the safety of GEN1046 as monotherapy and in combination therapies in patients 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.

  • Overall Status
  • Start Date
    May 14, 2019
  • Phase
    Phase 1, Phase 2
  • Study Type


Primary Outcome 1 - Measure: Dose limiting toxicity (DLT)

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

Primary Outcome 2 - Measure: Adverse events

Primary Outcome 2 - Timeframe: throughout the study and up to 2 months after last subject last treatment

Primary Outcome 3 - Measure: Safety laboratory parameters (hematology, biochemistry, coagulation, endocrines)

Primary Outcome 3 - Timeframe: throughout the study and up to 2 months after last subject last treatment

Primary Outcome 4 - Measure: For expansion cohort 1 only: Objective Response Rate (ORR)

Primary Outcome 4 - Timeframe: throughout the study and up to 2 months after last subject last treatment


  • Solid Tumors
  • Non-small Cell Lung Cancer
  • Urothelial Carcinoma
  • Endometrial Carcinoma
  • Triple Negative Breast Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Cervical Cancer


Key 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 two 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
Key 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
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No


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Overall Contact

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Phone: +4570202728



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