Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer

NCT ID: NCT05117242

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-27

Study Completion Date

2027-05-27

Brief Summary

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The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone (monotherapy) versus when it is combined with a cancer drug (pembrolizumab) for participants with relapsed/refractory (disease has returned after treatment or did not respond to treatment) non-small cell lung cancer (NSCLC; the most common type of lung cancer).

This trial has 2 parts. The purpose of the first part is to find out if the combination of acasunlimab and pembrolizumab is safe and to find out the best doses to use. The purpose of the second part is to give acasunlimab and pembrolizumab to more participants to evaluate efficacy. In the second part of the trial, participants will be randomized to participate in 1 of the 3 arms of the trial. Randomized means that the participant will be randomly assigned to a treatment arm based on chance; no one chooses their treatment arm.

Participants will receive either acasunlimab alone (100 followed by 500 mg into the vein) or acasunlimab with pembrolizumab (200 or 400 mg into the vein) once every 3 or 6 weeks, depending on which arm the participant is randomized into. All participants will receive active drug; no one will receive placebo.

Trial details include:

* The average trial duration for an individual participant will be about 10 months.
* The average treatment duration for an individual participant will be about 6 months.
* The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.

Detailed Description

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Conditions

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Non Small Cell Lung Cancer Metastatic

Keywords

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DuoBody® Bispecific antibody PD-L1 4-1BB

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

Treatment with acasunlimab once every 21 days for the first 2 cycles and then every 42 days in subsequent cycles

Group Type EXPERIMENTAL

Acasunlimab

Intervention Type BIOLOGICAL

Acasunlimab will be administered intravenously (IV)

Arm B

Treatment with acasunlimab + pembrolizumab once every 21 days

Group Type EXPERIMENTAL

Acasunlimab

Intervention Type BIOLOGICAL

Acasunlimab will be administered intravenously (IV)

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab will be administered IV

Arm C

Treatment with acasunlimab + pembrolizumab once every 42 days

Group Type EXPERIMENTAL

Acasunlimab

Intervention Type BIOLOGICAL

Acasunlimab will be administered intravenously (IV)

Pembrolizumab

Intervention Type BIOLOGICAL

Pembrolizumab will be administered IV

Interventions

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Acasunlimab

Acasunlimab will be administered intravenously (IV)

Intervention Type BIOLOGICAL

Pembrolizumab

Pembrolizumab will be administered IV

Intervention Type BIOLOGICAL

Other Intervention Names

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GEN1046 DuoBody®-PD-L1×4-1BB KEYTRUDA®

Eligibility Criteria

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Inclusion Criteria

* Have signed an informed consent form (ICF)
* Be at least 18 years of age.
* Have histologically or cytologically confirmed diagnosis of stage 4 NSCLC with at least 1 prior line of systemic therapy containing an anti-PD-1/PD-L1 mAb for metastatic disease
* Have a tumor PD-L1 expression result available prior to first treatment demonstrating PD-L1 expression in ≥1% of tumor cells as assessed by a central or local laboratory during screening.
* Have measurable disease per RECIST v1.1.
* Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
* Have life expectancy of at least 3 months.
* Have adequate organ and bone marrow function as defined in the protocol.

Exclusion Criteria

* Documentation of known EGFR, KRAS, RET, ROS1, BRAF mutations, NTRK gene infusions, RET arrangement, ALK gene rearrangements, high-level MET amplification, or METex 14 skipping. Note: Subjects harboring such mutations, gene rearrangements or amplifications may be enrolled in the trial, if subjects have received prior approved targeted therapy for such mutations, the subject may still be eligible for this trial.
* Treatment with an anti-cancer agent within 28 days prior to acasunlimab administration.
* Any investigational agent (including investigational vaccines).
* Radiotherapy within 14 days prior to first dose of acasunlimab. Note: palliative radiotherapy will be allowed for local pain control under certain conditions.
* Chronic systemic immunosuppressive corticosteroid doses, ie, prednisone \>10 mg daily or a cumulative dose \>150 mg prednisone within 14 days before the first acasunlimab administration.
* Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Subject has contraindications to the use of pembrolizumab per local prescribing information.
* Subject has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis (interstitial lung disease).
* 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 (within 6 months) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs.
* Subject has a known history of any of the following:

1. Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
2. Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.
3. Liver disease (eg, alcoholic hepatitis or non-alcoholic steatohepatitis, drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis).
4. 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.
5. Grade 3 or higher allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Genmab

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Official

Role: STUDY_DIRECTOR

Genmab

Locations

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St. Joseph Heritage Healthcare

Santa Rosa, California, United States

Site Status

Florida Cancer Specialists - FCS South

Fort Myers, Florida, United States

Site Status

Florida Cancer Center

St. Petersburg, Florida, United States

Site Status

Henry Ford Cancer Institute

Detroit, Michigan, United States

Site Status

Cancer & Hematology Centers of Western Michigan CHCWM P.C.

Grand Rapids, Michigan, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Hopital Morvan CHU de Brest

Brest, , France

Site Status

Hopital Charles Nicolle Chu Rouen

Rouen, , France

Site Status

Hopital dInstruction Des Armees Begin

Saint-Mandé, , France

Site Status

Institut de Cancerologie Strasbourg Europe (ICANS)

Strasbourg, , France

Site Status

Hôpital Foch

Suresnes, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Med.Hochschule Hannover Klinik für Pneumologie

Hanover, , Germany

Site Status

Universitatsklinik Giessen und Marburg Standort Giessen

Hessen, , Germany

Site Status

LKI Lungenfachklinik Immenhausen

Immenhausen, , Germany

Site Status

Department of Internal Medicine II

Regensburg, , Germany

Site Status

Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco

Catania, , Italy

Site Status

IRCCS Istituto Europeo di Oncologia

Milan, , Italy

Site Status

UOC Oncoematologia AOU L.Vanvitelli

Napoli, , Italy

Site Status

La Maddalena SPA

Palermo, , Italy

Site Status

IFO Regina Elena

Roma, , Italy

Site Status

Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status

VU University Medical Center

Amsterdam, , Netherlands

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, , Poland

Site Status

Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, , Poland

Site Status

Centro Clinico Champalimaud

Lisbon, , Portugal

Site Status

Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio

Porto, , Portugal

Site Status

Hospital Universitari Vall dHebron

Barcelona, , Spain

Site Status

Clinica Universidad de Navarra CUN

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

MD Anderson Cancer Center

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Fundacion Instituto Valenciano de Oncologia

Valencia, , Spain

Site Status

Cheltenham General Hospital

Cheltenham, , United Kingdom

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

Countries

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United States France Germany Italy Netherlands Poland Portugal Spain United Kingdom

Other Identifiers

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2021-001928-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1004314

Identifier Type: OTHER

Identifier Source: secondary_id

NL-OMON54259

Identifier Type: REGISTRY

Identifier Source: secondary_id

2024-513770-22-00

Identifier Type: OTHER

Identifier Source: secondary_id

RECF-005102

Identifier Type: REGISTRY

Identifier Source: secondary_id

15582

Identifier Type: REGISTRY

Identifier Source: secondary_id

GCT1046-04

Identifier Type: -

Identifier Source: org_study_id