GEN1046 Safety Trial in Patients With Malignant Solid Tumors

NCT ID: NCT03917381

Last Updated: 2026-02-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 429 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-14
• Study Completion Date: 2026-02-28

Brief Summary

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.

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.

Conditions

Solid Tumors

Study Design

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

Study Groups

Dose Escalation

Acasunlimab will be administered as monotherapy.

Group Type: EXPERIMENTAL

Acasunlimab

Intervention Type: BIOLOGICAL

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).

Expansion

Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts.

Group Type: EXPERIMENTAL

Acasunlimab

Intervention Type: BIOLOGICAL

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).

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

Intervention Type: BIOLOGICAL

Acasunlimab and docetaxel will be administered intravenously once every 21 days.

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

Intervention Type: BIOLOGICAL

Acasunlimab and pembrolizumab will be administered intravenously once every 21 days or every 42 days, respectively.

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

Intervention Type: BIOLOGICAL

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.

Interventions

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).

Intervention Type: BIOLOGICAL

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

Acasunlimab and docetaxel will be administered intravenously once every 21 days.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

GEN1046; DuoBody®-PD-L1x4-1BB; GEN1046; DuoBody®-PD-L1x4-1BB; GEN1046; DuoBody®-PD-L1x4-1BB; GEN1046; DuoBody®-PD-L1x4-1BB

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 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

Mayo Clinic

Phoenix, Arizona, United States

Yale University Cancer Center

New Haven, Connecticut, United States

Mayo Clinic

Jacksonville, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Iowa Hospitals

Iowa City, Iowa, United States

Norton Healthcare Inc

Louisville, Kentucky, United States

University of Michigan

Ann Arbor, Michigan, United States

START Midwest

Grand Rapids, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

NYU Langone

New York, New York, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Levine Cancer Institute, Atrium Health

Charlotte, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Fakultni nemocnice Brno

Brno, , Czechia

University Hospital Brno

Brno, , Czechia

Nemocnice AGEL Ostrava-Vítkovice a.s.

Nový Jičín, , Czechia

Fakultni nemocnice Olomouc

Olomouc, , Czechia

High Technology Hospital Medcenter

Batumi, , 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

Tbilisi, , Georgia

Onkologiai Klinika

Debrecen, , Hungary

BKMK Hospital

Kecskemét, , Hungary

Pulmonology Hospital Törökbálinti

Törökbálint, , Hungary

Rambam Health Care Campus RHCC - Rambam Medical Center

Haifa, , Israel

Hadassah Medical Organization HMO - Sharett Institute of Oncology

Jerusalem, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Sheba Medical Center, Ramat Gan

Tel Litwinsky, , Israel

Policlinico San'Orsola

Bologna, , Italy

IRCCS - Istituto Europeo di Oncologia IEO

Milan, , Italy

Istituto Nazionale Tumori - Fondazione Pascale Italy

Napoli, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

AUSL Romagno-Ravenna

Ravenna, , Italy

Policlinico Uni. Campus Bio-Medico

Roma, , Italy

Regina Elena National Cancer Institute

Rome, , Italy

ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "

Varese, , Italy

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Medpolonia Sp. z o.o.

Poznan, , Poland

Specialist Hospital in Prabuty

Prabuty, , Poland

Dom Lekarski SA

Szczecin, , Poland

Maria Sklodowska Curie National Research Instutute of Oncology

Warsaw, , Poland

Hospital Universitario Vall dHebron

Barcelona, , Spain

IOB-Hospital Quironsalud Barcelona

Barcelona, , Spain

START Madrid-FJD, Hospital Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

START Madrid-CIOCC

Madrid, , Spain

NEXT Oncology Madrid

Madrid, , Spain

Hospital Universitario La Princesa

Madrid, , Spain

MD Anderson Cancer Center Madrid

Madrid, , Spain

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Hospital Clinico De Valencia

Valencia, , Spain

Gulhane Training and Research Hospital

Ankara, , Turkey (Türkiye)

Trakya University Hospital

Edirne, , Turkey (Türkiye)

Medical Point Izmir Hospital

Karşıyaka, , Turkey (Türkiye)

ARENSIA Exploratory Medicine LLC

Kyiv, , Ukraine

Countries

United States; Czechia; Georgia; Hungary; Israel; Italy; Poland; Spain; Turkey (Türkiye); Ukraine

References

Muik A, Garralda E, Altintas I, Gieseke F, Geva R, Ben-Ami E, Maurice-Dror C, Calvo E, LoRusso PM, Alonso G, Rodriguez-Ruiz ME, Schoedel KB, Blum JM, Sanger B, Salcedo TW, Burm SM, Stanganello E, Verzijl D, Vascotto F, Sette A, Quinkhardt J, Plantinga TS, Toker A, van den Brink EN, Fereshteh M, Diken M, Satijn D, Kreiter S, Breij ECW, Bajaj G, Lagkadinou E, Sasser K, Tureci O, Forssmann U, Ahmadi T, Sahin U, Jure-Kunkel M, Melero I. Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors. Cancer Discov. 2022 May 2;12(5):1248-1265. doi: 10.1158/2159-8290.CD-21-1345.

Reference Type: DERIVED

PMID: 35176764 (View on PubMed)

Other Identifiers

2018-003402-63

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOH_2019-05-08_006011

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-509059-15

Identifier Type: OTHER

Identifier Source: secondary_id

GCT1046-01

Identifier Type: -

Identifier Source: org_study_id