GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies

NCT04937153 | Completed Phase 1 FDA Drug

• 2 other identifiers: GCT1046-02jRCT2031210112
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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 Outcomes (1)

• Number of Participants with Anti-Drug Antibody (ADA) to Acasunlimab

  Up to 2 years

Study Arms (2)

acasunlimab monotherapy

EXPERIMENTAL

Biological: Acasunlimab

acasunlimab + pembrolizumab combination therapy

EXPERIMENTAL

Biological: Acasunlimab; Biological: Pembrolizumab

Interventions

Acasunlimab BIOLOGICAL

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

Also known as: GEN1046, DuoBody®-PD-L1x4-1BB

acasunlimab + pembrolizumab combination therapy; acasunlimab monotherapy

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered IV once every 21 days.

acasunlimab + pembrolizumab combination therapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genmab: lead

Study Sites (2)

National Cancer Center East

Chiba, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The starting dose is 15 mg administered as a flat dose. Dose escalation steps are based on safety data.

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: June 23, 2021
• Study Start: June 15, 2021
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2)