GEN1046 Safety Trial in Patients With Malignant Solid Tumors

NCT03917381 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: GCT1046-012018-003402-63MOH_2019-05-08_0060112023-509059-15
• Study Type: interventional
• Target: 429
• Locations: 10 countries
• Sites: 57

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Dose Escalation: Number of Participants With Dose Limiting Toxicity (DLT)

  Toxicities will be graded for severity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 5.0.

  During first cycle (21 days) for each cohort

• Dose Escalation and Monotherapy Expansion Cohorts: Number of Participants With Adverse Events (AEs)

  From first dose until the end of the study (up to 60 days after the last dose)

• Expansion Cohort 1: Objective Response Rate (ORR)

  ORR is 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 tumours (RECIST).

  Up to 3 years

Secondary Outcomes (10)

• Expansion Cohort 1: Number of Participants With AEs

  From first dose until the end of the study (up to 60 days after the last dose)

• Combination Therapy Expansion Cohorts: Number of Participants With AEs

  From first dose until the end of the study (up to 60 days after the last dose)

• All Parts: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUClast) of GEN1046

  Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose)

• All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1046

  Predose and postdose at multiple timepoints up to end of safety follow up (up to 60 days after last dose)

• All Parts: Number of Participants with Anti-drug Antibodies (ADAs)

  Up to 3 years

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Acasunlimab will be administered as monotherapy.

Biological: Acasunlimab

Expansion

EXPERIMENTAL

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

Biological: Acasunlimab; Biological: Acasunlimab in combination with docetaxel (in a single expansion cohort); Biological: Acasunlimab in combination with pembrolizumab (in a separate expansion cohort); Biological: Acasunlimab in combination with pembrolizumab and standard chemotherapy (in separate expansion cohorts)

Interventions

Acasunlimab 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).

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

Dose Escalation; Expansion

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

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

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

Expansion

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

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

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

Expansion

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

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

Expansion

Eligibility Criteria

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

You may qualify if:

• 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

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
• 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

Sponsors & Collaborators

• Genmab: lead

Study Sites (57)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Yale University Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals

Iowa City, Iowa, 52242, United States

Location

Norton Healthcare Inc

Louisville, Kentucky, 40202, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

UNC Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Levine Cancer Institute, Atrium Health

Charlotte, North Carolina, 28204, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Fakultni nemocnice Brno

Brno, Czechia

Location

University Hospital Brno

Brno, Czechia

Location

Nemocnice AGEL Ostrava-Vítkovice a.s.

Nový Jičín, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, Czechia

Location

High Technology Hospital Medcenter

Batumi, Georgia

Location

LLC "TIM - Tbilisi Institute of Medicine"

Tbilisi, Georgia

Location

LTD Consilium Medulla

Tbilisi, Georgia

Location

Tbilisi State Medical University and Ingorovka High Medical Technology University Clinic Ltd

Tbilisi, Georgia

Location

Onkologiai Klinika

Debrecen, Hungary

Location

BKMK Hospital

Kecskemét, Hungary

Location

Pulmonology Hospital Törökbálinti

Törökbálint, Hungary

Location

Rambam Health Care Campus RHCC - Rambam Medical Center

Haifa, Israel

Location

Hadassah Medical Organization HMO - Sharett Institute of Oncology

Jerusalem, 12000, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Sheba Medical Center, Ramat Gan

Tel Litwinsky, 52621, Israel

Location

Policlinico San'Orsola

Bologna, Italy

Location

IRCCS - Istituto Europeo di Oncologia IEO

Milan, Italy

Location

Istituto Nazionale Tumori - Fondazione Pascale Italy

Naples, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, Italy

Location

AUSL Romagno-Ravenna

Ravenna, Italy

Location

Policlinico Uni. Campus Bio-Medico

Roma, Italy

Location

Regina Elena National Cancer Institute

Rome, Italy

Location

ASST Sette Laghi "Ospedale di Circolo e Fondazione Macchi "

Varese, Italy

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Location

Medpolonia Sp. z o.o.

Poznan, Poland

Location

Specialist Hospital in Prabuty

Prabuty, Poland

Location

Dom Lekarski SA

Szczecin, Poland

Location

Maria Sklodowska Curie National Research Instutute of Oncology

Warsaw, Poland

Location

Hospital Universitario Vall dHebron

Barcelona, 08035, Spain

Location

IOB-Hospital Quironsalud Barcelona

Barcelona, 8023, Spain

Location

START Madrid-FJD, Hospital Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

START Madrid-CIOCC

Madrid, 28050, Spain

Location

NEXT Oncology Madrid

Madrid, 28223, Spain

Location

Hospital Universitario La Princesa

Madrid, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Clinico De Valencia

Valencia, 46010, Spain

Location

Gulhane Training and Research Hospital

Ankara, Turkey (Türkiye)

Location

Medical Point Izmir Hospital

Cordaleo, Turkey (Türkiye)

Location

Trakya University Hospital

Edirne, Turkey (Türkiye)

Location

ARENSIA Exploratory Medicine LLC

Kyiv, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 35176764 DERIVED

MeSH Terms

Interventions

Docetaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 17, 2019
• Study Start: May 14, 2019
• Primary Completion: April 1, 2025
• Study Completion: February 1, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GE (4); IT (8); UA (1); HU (3); US (14); TU (3); IL (4); ES (11); PL (5); CZ (4)