GEN1046 Safety Trial in Patients With Malignant Solid Tumors

August 17, 2026 updated by: Genmab

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

The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together with standard of care treatment (docetaxel) or another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of patients with certain types of cancer. All subjects will receive active drug; no one will receive placebo.

This trial has 2 parts. The purpose of the first part is to find out if acasunlimab at various doses is safe and to find out the best doses of acasunlimab to use. The purpose of the second part is to give acasunlimab to more subjects to see how well the doses of acasunlimab selected in the first part work against cancer when given alone and how well they work when given with pembrolizumab with or without chemotherapy.

Trial details include:

  • The average trial duration for an individual subject will be about 74 weeks.
  • The average treatment duration for an individual subject will be about 21 weeks.
  • The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The trial is an open-label, multi-center safety trial of acasunlimab (GEN1046). The trial consists of 2 consecutive parts: a first-in-human (FIH) dose escalation (phase 1) and an expansion (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.

Study Type

Interventional

Enrollment (Actual)

429

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Brno, Czechia
        • Fakultni nemocnice Brno
      • Brno, Czechia
        • University Hospital Brno
      • Nový Jičín, Czechia
        • Nemocnice AGEL Ostrava-Vítkovice a.s.
      • Olomouc, Czechia
        • Fakultni Nemocnice Olomouc
  • Georgia
      • Batumi, Georgia
        • High Technology Hospital Medcenter
      • Tbilisi, Georgia
        • LLC "TIM - Tbilisi Institute of Medicine"
      • Tbilisi, Georgia
        • LTD Consilium Medulla
      • Tbilisi, Georgia
        • Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd
  • Hungary
      • Debrecen, Hungary
        • Onkologiai Klinika
      • Kecskemét, Hungary
        • BKMK Hospital
      • Törökbálint, Hungary
        • Pulmonology Hospital Törökbálinti
  • Israel
      • Haifa, Israel
        • Rambam Health Care Campus RHCC - Rambam Medical Center
      • Jerusalem, Israel, 12000
        • Hadassah Medical Organization HMO - Sharett Institute of Oncology
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
      • Tel Litwinsky, Israel, 52621
        • Sheba Medical Center, Ramat Gan
  • Italy
      • Bologna, Italy
        • Policlinico San'Orsola
      • Milan, Italy
        • IRCCS - Istituto Europeo di Oncologia IEO
      • Naples, Italy
        • Istituto Nazionale Tumori - Fondazione Pascale Italy
      • Parma, Italy
        • Azienda Ospedaliero Universitaria di Parma
      • Ravenna, Italy
        • AUSL Romagno-Ravenna
      • Roma, Italy
        • Policlinico Uni. Campus Bio-Medico
      • Rome, Italy
        • Regina Elena National Cancer Institute
      • Varese, Italy
        • ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "
  • Poland
      • Gdansk, Poland
        • Uniwersyteckie Centrum Kliniczne
      • Poznan, Poland
        • Medpolonia Sp. z o.o.
      • Prabuty, Poland
        • Specialist Hospital in Prabuty
      • Szczecin, Poland
        • Dom Lekarski SA
      • Warsaw, Poland
        • Maria Sklodowska Curie National Research Instutute of Oncology
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall Dhebron
      • Barcelona, Spain, 8023
        • IOB-Hospital Quironsalud Barcelona
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28040
        • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
      • Madrid, Spain
        • MD Anderson Cancer Center Madrid
      • Madrid, Spain
        • Hospital Universitario La Princesa
      • Madrid, Spain, 28050
        • START Madrid-CIOCC
      • Madrid, Spain, 28223
        • NEXT Oncology Madrid
      • Málaga, Spain
        • Hospital Universitario Virgen de la Victoria
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Valencia, Spain, 46010
        • Hospital Clínico de Valencia
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye)
        • Gulhane Training and Research Hospital
      • Cordaleo, Turkey (Türkiye)
        • Medical Point Izmir Hospital
      • Edirne, Turkey (Türkiye)
        • Trakya University Hospital
  • Ukraine
      • Kyiv, Ukraine
        • ARENSIA Exploratory Medicine LLC
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8028
        • Yale University Cancer Center
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Healthcare Inc
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Grand Rapids, Michigan, United States, 49546
        • START MidWest
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10016
        • NYU Langone
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • UNC Chapel Hill
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute, Atrium Health
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Acasunlimab will be administered as monotherapy.
Biological: Acasunlimab
Acasunlimab will be administered intravenously once every 21 days (in selected expansion cohorts acasunlimab will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles).
Other Names:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Experimental: Expansion
Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts.
Biological: Acasunlimab
Acasunlimab will be administered intravenously once every 21 days (in selected expansion cohorts acasunlimab will be administered intravenously once every 21 days for the first 2 cycles, and every 42 days in subsequent cycles).
Other Names:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort)
Acasunlimab and docetaxel will be administered intravenously once every 21 days.
Other Names:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biological: Acasunlimab in combination with pembrolizumab (in a separate expansion cohort)
Acasunlimab and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively.
Other Names:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB
Biological: Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)
Acasunlimab and pembrolizumab and standard chemotherapy will be administered intravenously once every 21 days for 4 cycles, followed by treatment with acasunlimab and pembrolizumab once every 21 days.
Other Names:
  • GEN1046
  • DuoBody®-PD-L1x4-1BB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)
Time Frame: During first cycle (21 days)
In this trial, a DLT was defined as any grade 5 toxicity, grade 4 neutropenia lasting more than 7 days, grade 3 and 4 febrile neutropenia, grade 4 thrombocytopenia for minimal duration of 7 days, grade 3&4 hemorrhage associated with thrombocytopenia of ≥ grade 3 requiring platelet transfusion, grade 4 anemia, liver toxicity (transaminases and bilirubin elevations), grade 3 nausea that didn't respond to optimal antiemetic treatment within 7 days, grade ≥3 vomiting that didn't respond to optimal antiemetic treatment within 3 days, grade ≥3 diarrhea that didn't respond to optimal antidiarrheal treatment within 3 days, grade 3 immune-related adverse event (irAEs) that didn't improve to ≤ grade 1 within 7 days by appropriate care or with corticosteroids (with exceptions per protocol), any grade 4 irAE, any other ≥ grade 3 non-hematological adverse events (AE), which occurred during the first GEN1046 treatment cycle (with exceptions per protocol).
During first cycle (21 days)
Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Treatment-emergent Adverse Events (AEs)
Time Frame: Up to approximately 5 years, 10 months
An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 5 years, 10 months
Expansion Cohort 1: Objective Response Rate (ORR)
Time Frame: Up to approximately 5 years, 10 months
ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on response evaluation criteria in solid tumors (RECIST v1.1). CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 millimeters (mm). PR was defined as ≥30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs.
Up to approximately 5 years, 10 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combination Therapy Expansion Cohorts: Number of Participants With Treatment-emergent AEs
Time Frame: Up to approximately 5 years, 10 months
An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Treatment-emergent AEs were any AEs that developed or worsened after the first dose of a medicinal product. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Up to approximately 5 years, 10 months
Dose Escalation: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2.
Cycle 1 and Cycle 2 (cycles were 21 days)
Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of GEN1046
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
Venous blood samples were collected for measurement of plasma concentrations of GEN1046. Data reported are average values for Cycle 1 and Cycle 2.
Cycle 1 and Cycle 2 (cycles were 21 days)
Number of Participants With Anti-drug Antibodies (ADAs) to GEN1046
Time Frame: Up to approximately 5 years, 10 months
Venous blood samples were collected for measurement of serum concentrations of ADAs. A participant was considered as positive overall status if: (i) negative at baseline and at least one positive post-baseline result; or (ii) positive at baseline and at least one positive post-baseline result with a titer higher than baseline.
Up to approximately 5 years, 10 months
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: ORR
Time Frame: Up to approximately 5 years, 10 months
ORR was defined as the percentage of participants with BOR of CR or PR based on RECIST. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs.
Up to approximately 5 years, 10 months
Dose Escalation and Expansion Cohorts 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13: Disease Control Rate (DCR)
Time Frame: Up to approximately 5 years, 10 months
DCR was defined as the percentage of participants with confirmed BOR of CR, PR, or stable disease (SD) according to RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes must have had a reduction in short axis to <10 mm. PR was defined as ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of LDs. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Follow-up measurements must have met the SD criteria at least once and for a minimum time period of 6 weeks (±7 days) after first treatment.
Up to approximately 5 years, 10 months
Duration of Response (DoR)
Time Frame: Up to approximately 5 years, 10 months
DOR was defined as the time from first documentation of response (CR or PR) to the date of the first documented progression or death whichever occurred earlier based on RECIST v1.1. DOR only applied to participants whose confirmed best overall response was CR or PR (i.e., responders).
Up to approximately 5 years, 10 months
Expansion Cohort 1: Progression Free Survival (PFS)
Time Frame: Up to approximately 5 years, 10 months
PFS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to the first documented progression or death due to any cause, whichever occurred first based on RECIST version 1.1.
Up to approximately 5 years, 10 months
Expansion Cohort 1: Overall Survival (OS)
Time Frame: Up to approximately 5 years, 10 months
OS was defined as the time from Day 1 in Cycle 1 (cycles were 21 days) to death due to any cause.
Up to approximately 5 years, 10 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genmab

Collaborators

BioNTech SE

Investigators

  • Study Director: Study Official, Genmab

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2019

Primary Completion (Actual)

April 1, 2025

Study Completion (Actual)

August 3, 2026

Study Registration Dates

First Submitted

April 11, 2019

First Submitted That Met QC Criteria

April 12, 2019

First Posted (Actual)

April 17, 2019

Study Record Updates

Last Update Posted (Actual)

September 9, 2026

Last Update Submitted That Met QC Criteria

August 17, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCT1046-01
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2018 (U.S. NIH Grant/Contract)
  • 2018-003402-63 (EudraCT Number)
  • MOH_2019-05-08_006011 (Registry Identifier: Clinical Research Site - mytrial)
  • 2023-509059-15 (Other Identifier: EU Trial (CTIS) Number)

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe