GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies

Open-label, Dose-escalation Trial to Evaluate the Safety and Pharmacokinetics of GEN1046 in Japanese Subjects With Advanced Solid Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Biological: Acasunlimab; Biological: Pembrolizumab

Detailed Description

The purpose of the trial is to evaluate the safety and pharmacokinetics of GEN1046 in Japanese subjects with malignant solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • National Cancer Center East
  • Tokyo, Japan
    • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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.

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.
  • 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.

Note: Other protocol specified inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: acasunlimab monotherapy	Biological: Acasunlimab; Acasunlimab will be administered intravenously (IV) once every 21 days.; Other Names: GEN1046; DuoBody®-PD-L1x4-1BB
Experimental: acasunlimab + pembrolizumab combination therapy	Biological: Acasunlimab; Acasunlimab will be administered intravenously (IV) once every 21 days.; Other Names: GEN1046; DuoBody®-PD-L1x4-1BB; Biological: Pembrolizumab; Pembrolizumab will be administered IV once every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From first dose date up to end of the safety follow up period, 90 days after last dose
Number of Participants with Dose limiting Toxicities (DLTs)	Determine the DLT profile of acasunlimab administered as monotherapy or in combination with pembrolizumab. The DLTs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.	During first cycle (Cycle length=21 days) in each cohort
Area under the concentration time curve (AUC) of Acasunlimab		Predose and postdose at multiple timepoints of each cycle (Cycle length=21 days)
Maximum (Peak) Plasma Concentration (Cmax) of Acasunlimab		Predose and postdose at multiple timepoints of each cycle (Cycle length=21 days)
Time to Reach Cmax (Tmax) of Acasunlimab		Predose and postdose at multiple timepoints of each cycle (Cycle length=21 days)
Plasma Trough (Pre-dose) Concentrations (Cthrough) of Acasunlimab		Predose and postdose at multiple timepoints of each cycle (Cycle length=21 days)
Elimination half-life (t 1/2) of Acasunlimab		Predose and postdose at multiple timepoints of each cycle (Cycle length=21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Anti-Drug Antibody (ADA) to Acasunlimab	Serum samples will be screened for ADAs to acasunlimab and the titer of confirmed positive samples will be reported.	Up to 2 years

Collaborators and Investigators

• Sponsor: Genmab
• Collaborators: BioNTech SE
• Investigators: Study Director: Study Official, Genmab

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): October 1, 2024
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: GCT1046-02; jRCT2031210112 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes