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

NCT05117242 | Active Not Recruiting Phase 2 FDA Drug

• 7 other identifiers: GCT1046-042021-001928-171004314NL-OMON542592024-513770-22-00RECF-00510215582
• Study Type: interventional
• Target: 125
• Locations: 9 countries
• Sites: 40

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer Metastatic

Keywords

DuoBody®; Bispecific antibody; PD-L1; 4-1BB

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR will be measured as the proportion of subjects with a confirmed response of complete response (CR) or partial response (PR) as per RECIST v1.1

  From first treatment to approximately 27 weeks after last subject's first dose

Secondary Outcomes (5)

• Duration of response (DOR)

  From onset date of response until disease progression/death/lost to follow-up/start of new anticancer therapy or withdrawal of consent, whichever occurs first (an expected average of 6 months)

• Time to response (TTR)

  From first treatment to date of onset of initial response (CR or PR) as per RECIST v.1.1 (an expected average of 6 months)

• Progression-free survival (PFS)

  From first treatment to first documented progression or death due to any cause (an expected average of 6 months)

• Overall survival (OS)

  From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)

• Incidence and severity of adverse events (AEs) and laboratory abnormalities

  Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)

Study Arms (3)

Arm A

EXPERIMENTAL

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

Biological: Acasunlimab

Arm B

EXPERIMENTAL

Treatment with acasunlimab + pembrolizumab once every 21 days

Biological: Acasunlimab; Biological: Pembrolizumab

Arm C

EXPERIMENTAL

Treatment with acasunlimab + pembrolizumab once every 42 days

Biological: Acasunlimab; Biological: Pembrolizumab

Interventions

Acasunlimab BIOLOGICAL

Acasunlimab will be administered intravenously (IV)

Also known as: GEN1046, DuoBody®-PD-L1×4-1BB

Arm A; Arm B; Arm C

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered IV

Also known as: KEYTRUDA®

Arm B; Arm C

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Grade 3 or higher irAEs that led to treatment discontinuation of a prior immunotherapy treatment.
• Myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade.

Sponsors & Collaborators

• Genmab: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (40)

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Florida Cancer Specialists - FCS South

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Center

St. Petersburg, Florida, 33705, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

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

Grand Rapids, Michigan, 49503, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Institut Bergonie

Bordeaux, France

Location

Hopital Morvan CHU de Brest

Brest, France

Location

Hopital Charles Nicolle Chu Rouen

Rouen, France

Location

Hopital dInstruction Des Armees Begin

Saint-Mandé, France

Location

Institut de Cancerologie Strasbourg Europe (ICANS)

Strasbourg, France

Location

Hôpital Foch

Suresnes, France

Location

Gustave Roussy

Villejuif, France

Location

Med.Hochschule Hannover Klinik für Pneumologie

Hanover, Germany

Location

Universitatsklinik Giessen und Marburg Standort Giessen

Hessen, Germany

Location

LKI Lungenfachklinik Immenhausen

Immenhausen, Germany

Location

Department of Internal Medicine II

Regensburg, Germany

Location

Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco

Catania, Italy

Location

IRCCS Istituto Europeo di Oncologia

Milan, Italy

Location

UOC Oncoematologia AOU L.Vanvitelli

Naples, Italy

Location

La Maddalena SPA

Palermo, Italy

Location

IFO Regina Elena

Roma, Italy

Location

Netherlands Cancer Institute

Amsterdam, Netherlands

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, Poland

Location

Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, Poland

Location

Centro Clinico Champalimaud

Lisbon, Portugal

Location

Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio

Porto, Portugal

Location

Hospital Universitari Vall dHebron

Barcelona, Spain

Location

Clinica Universidad de Navarra CUN

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, Spain

Location

Cheltenham General Hospital

Cheltenham, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 11, 2021
• Study Start: October 27, 2021
• Primary Completion: December 2, 2024
• Study Completion (Estimated): August 30, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2); US (6); FR (7); IT (5); GB (2); NL (4); ES (8); PT (2); DE (4)