GEN1046 Safety Trial in Patients With Malignant Solid Tumors

Genmab

Status and phase: Active, not recruiting; Phase 2; Phase 1

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

Treatments: Biological: Acasunlimab in combination with pembrolizumab (in a separate expansion cohort); Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort); Biological: Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts); Biological: Acasunlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03917381

2023-509059-15-00 (EU Trial (CTIS) Number)

MOH_2019-05-08_006011 (Registry Identifier)

GCT1046-01

2018-003402-63 (EudraCT Number)

Details and patient eligibility

About

The purpose of the trial is to evaluate the safety of acasunlimab (also known as GEN1046) as monotherapy and in combination therapies in patients with malignant solid tumors

Full description

The trial is an open-label, multi-center safety trial of acasunlimab (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.

Enrollment: 429 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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429 participants in 2 patient groups

Dose escalation

Experimental group

Description:

Acasunlimab will be administered as monotherapy

Treatment:

Biological: Acasunlimab

Expansion

Experimental group

Description:

Acasunlimab will be administered as monotherapy (or in combination with docetaxel or in combination with pembrolizumab or in combination with pembrolizumab and standard chemotherapy in separate expansion cohorts)

Treatment:

Biological: Acasunlimab

Biological: Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)

Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort)

Biological: Acasunlimab in combination with pembrolizumab (in a separate expansion cohort)