GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies

NCT ID: NCT04937153

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2024-10-01

Brief Summary

The primary objective of the study is to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and pharmacokinetics (PK) of acasunlimab (also known as GEN1046) administered as monotherapy or in combination with pembrolizumab in Japanese study participants with malignant solid tumors.

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

acasunlimab monotherapy

Group Type: EXPERIMENTAL

Acasunlimab

Intervention Type: BIOLOGICAL

Acasunlimab will be administered intravenously (IV) once every 21 days.

acasunlimab + pembrolizumab combination therapy

Group Type: EXPERIMENTAL

Acasunlimab

Intervention Type: BIOLOGICAL

Acasunlimab will be administered intravenously (IV) once every 21 days.

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab will be administered IV once every 21 days.

Interventions

Acasunlimab

Acasunlimab will be administered intravenously (IV) once every 21 days.

Intervention Type: BIOLOGICAL

Pembrolizumab

Pembrolizumab will be administered IV once every 21 days.

Intervention Type: BIOLOGICAL

Other Intervention Names

GEN1046; DuoBody®-PD-L1x4-1BB

Eligibility Criteria

Inclusion Criteria

• Participant must have a histologically-confirmed non-central nervous system (CNS) solid tumor that is metastatic or unresectable and for whom there is no available standard therapy likely to confer clinical benefit; or a participant who is not a candidate for such available therapy and for whom, in the opinion of the investigator, experimental therapy with acasunlimab or acasunlimab in combination with pembrolizumab may be beneficial.
• Asian race and Japanese ethnicity.
• Have measurable disease according to Response Evaluation Criteria in Solid Tumors (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.
• Should provide a tumor tissue sample (formalin-fixed paraffin-embedded [FFPE] blocks/slides) from archival tissue or fresh biopsy collected before C1D1, preferably derived from advanced disease stage.

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.
• Evidence of interstitial lung disease.
• 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 trial treatment.
• 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 the first dose of trial treatment. 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 trial treatment administration.
• Toxicities from previous anti-cancer therapies that have not adequately resolved.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genmab

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Official

Role: STUDY_DIRECTOR

Genmab

Locations

National Cancer Center East

Chiba, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Countries

Japan

Other Identifiers

jRCT2031210112

Identifier Type: REGISTRY

Identifier Source: secondary_id

GCT1046-02

Identifier Type: -

Identifier Source: org_study_id