Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)

A Prospective, Open-Label, Randomized, Phase 3 Trial of Acasunlimab (GEN1046) in Combination With Pembrolizumab Versus Docetaxel in Subjects With PD-L1 Positive Metastatic Non-Small Cell Lung Cancer After Treatment With a PD-1/PD-L1 Inhibitor and Platinum-Containing Chemotherapy (ABBIL1TY NSCLC-06)

This is a multicenter, randomized, open-label, international, Phase 3 trial to evaluate the efficacy and safety of acasunlimab in combination with pembrolizumab versus docetaxel (standard of care) in participants with locally advanced (unresectable stage IIIB/C) or programmed death ligand 1 (PD-L1)-positive metastatic non-small cell lung cancer (NSCLC) who have been treated with programmed cell death protein 1 (PD-1)/PD-L1 inhibitor and platinum-containing chemotherapy, administered either in combination or sequentially in the locally advanced (unresectable stage IIIB/C) or metastatic setting.

Study Overview

• Status: Active, not recruiting
• Conditions: PD-L1-positive, Locally Advanced (Unresectable Stage IIIB/C) or Metastatic NSCLC
• Intervention / Treatment: Drug: Docetaxel; Drug: Pembrolizumab; Drug: Acasunlimab

Detailed Description

The goal of this trial is to determine the efficacy and safety of acasunlimab (an experimental antibody also known as GEN1046 or DuoBody® PDL1x4-1BB) in combination with pembrolizumab (an antibody known as KEYTRUDA®) compared to that of docetaxel (a standard of care chemotherapy). During the trial, the participant's quality of life will also be evaluated using industry-standard scales of measurement. To be eligible, participants must have:

1. non-small cell lung cancer that are locally advanced, unresectable stage IIIB/C or has metastasized (spread)
2. tumors that are positive for the PD-L1 protein (a biomarker that may be predictive of response to therapy)
3. been previously treated with a PD-1/PD-L1-inhibitor and a platinum-containing cancer therapy administered in combination or sequentially (irrespective of the order).

Other eligibility criteria will also apply.

Participants will be assigned to 1 of 2 active therapies, also known as treatment arms, as follows:

• Acasunlimab (100 milligrams [mg]) and pembrolizumab (400 mg) once every 6 weeks (Q6W), or
• Docetaxel 75 milligrams per meter squared (mg/m^2) once every 3 weeks (Q3W).

The estimated trial duration for a participant will vary but may be up to 5 years, consisting of:

• An optional 3-month pre-screening period
• A 28-day screening period
• Up to 2 years of treatment
• A 90-day safety follow-up period
• Post-treatment follow-up.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
    • Hospital Italiano de Buenos Aires
  • La Rioja, Argentina
    • Investigaciones CORI S.R.L.
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina
      • Hospital Italiano de La Plata
    • Pergamino, Buenos Aires, Argentina
      • Centro de Investigacion Pergamino S.A.
  • Ciudad Autonoma Buenos Aires
    • Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina
      • Instituto Medico Especializado Alexander Fleming
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina
      • Sanatorio Parque S.A.
• Australia
  • Fitzroy, Australia
    • St Vincent's Hospital Melbourne
  • Wendouree, Australia
    • Ballarat Oncology & Haematology Service
  • New South Wales
    • Camperdown, New South Wales, Australia
      • Chris OBrien LifeHouse
    • Sydney, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Southport, Queensland, Australia
      • Gold Coast Hospital
  • South Australia
    • Bedford Park, South Australia, Australia
      • Flinders Medical Centre
  • Western Australia
    • Perth, Western Australia, Australia
      • Sir Charles Gairdner Hospital
    • Subiaco, Western Australia, Australia
      • St John of God Subiaco Hospital
• Austria
  • Linz, Austria
    • Kepler Universitatsklinikum Med Campus III
  • Rankweil, Austria
    • LKH - Rankweil
  • Vienna, Austria
    • Standort Penzing der Klinik Ottakring
  • Vienna, Austria
    • Wiener Gesundheitsverbund - Klinik Floridsdorf
• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint-luc
  • Brussels, Belgium
    • C. H. U. St-Pierre
  • Brussels, Belgium
    • Universitair Ziekenhuis Bruxelles
  • Gilly, Belgium
    • Grand Hôpital de Charleroi
  • Hasselt, Belgium
    • Jessa Ziekenhuis Hospital
  • Liège, Belgium
    • CHU de Liège
  • Mechelen, Belgium
    • AZ Sint-Maarten
  • Roeselare, Belgium
    • AZ Delta
• Brazil
  • Belo Horizonte, Brazil
    • Oncoclínicas do Brasil Serviços Médicos SA
  • Porto Alegre, Brazil
    • Hospital Ernesto Dornelles
  • Rio de Janeiro, Brazil
    • OncoClinicas Rio de Janeiro
  • Santo André, Brazil
    • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • Paraná
    • Curitiba, Paraná, Brazil
      • Hospital Erasto Gaertner
  • Pernambuco
    • Recife, Pernambuco, Brazil
      • MultiHemo Servicos Medicos
  • Rio Do Janeiro
    • Rio de Janeiro, Rio Do Janeiro, Brazil
      • Instituto D'Or Pesquisa e Ensino - Rio de Janeiro
  • Rio Grande Do Su
    • Porto Alegre, Rio Grande Do Su, Brazil
      • Hospital Sao Lucas Da Pucrs
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil
      • Hospital de Clinicas de Ijui
    • Porto Alegre, Rio Grande do Sul, Brazil
      • Centro Gaucho Integrado - Mae de Deus Center
  • Santa Catarina
    • Itajaí, Santa Catarina, Brazil
      • Clínica de Neoplasias Litoral Ltda.
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • BP A Beneficencia Portuguesa de Sao Paulo
    • São Paulo, São Paulo, Brazil
      • Centro Paulista de Oncologia S.A.
    • São Paulo, São Paulo, Brazil
      • Hospital Sirio-Libanes
• Bulgaria
  • Pleven, Bulgaria
    • MHAT Heart and Brain - Pleven
  • Plovdiv, Bulgaria
    • Complex Oncology Center - Plovdiv, EOOD
  • Sofia, Bulgaria
    • UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria
    • MHAT for women's health - Nadezhda, OOD
  • Sofia, Bulgaria
    • MHAT "Serdika", EOOD
  • Sofia, Bulgaria
    • UMHAT 'SofiaMed', OOD
• Canada
  • Ontario
    • Brampton, Ontario, Canada
      • William Osler Health System-Brampton Civic Hospital|William Osler Health System
    • Kingston, Ontario, Canada
      • Kingston Health Sciences Centre
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Centre - University Health Network
  • Quebec
    • Montreal, Quebec, Canada
      • MUHC - Jewish General Hospital
• Chile
  • Providencia, Chile
    • FALP - Fundación Arturo López Pérez
  • Santiago, Chile
    • Centro de Investigacion Clinica Bradford Hill
  • Santiago, Chile
    • IRAM - Instituto de Radio Medicina
  • Viña del Mar, Chile
    • Oncocentro APYS
• Croatia
  • Dubrovnik, Croatia
    • General Hospital Dubrovnik
  • Rijeka, Croatia
    • Specialty Hospital Medico
  • Zagreb, Croatia
    • Sestre milosrdnice University Hospital Center
  • Zagreb, Croatia
    • Department for Pulmonary Diseases University Hospital Centre Zagreb
• Estonia
  • Tallinn, Estonia
    • North Estonia Medical Centre Foundation
  • Tartu, Estonia
    • Tartu University Hospital
• France
  • Angers, France
    • CHU Angers - Hôpital Larrey
  • Bayonne, France
    • Centre Hospitalier de la Cote Basque
  • Boulogne-Billancourt, France
    • Hôpital Ambroise Paré
  • Créteil, France
    • Centre Hospitalier Intercommunal de Creteil (CHIC)
  • Lille, France
    • Hopital Albert Calmette - CHU Lille
  • Lyon, France
    • Centre Leon Berard
  • Marseille, France
    • Assistance Publique-Hôpitaux de Marseille
  • Mulhouse, France
    • CH de Mulhouse - Hôpital Emile Muller
  • Nantes, France
    • Hôpital Privé du Confluent
  • Paris, France
    • Institut Curie
  • Paris, France
    • Hopital Saint Joseph - Paris
  • Rennes, France
    • Chu Rennes - Hopital Pontchaillou
  • Saint-Herblain, France
    • ICO - Site René Gauducheau
  • Toulon, France
    • Hôpital Sainte Musse
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France
      • Institut Paoli Calmettes
  • Gironde
    • Bordeaux, Gironde, France
      • Institut Bergonie
  • Pyrenees Atlantiques
    • Bayonne, Pyrenees Atlantiques, France
      • Clinique Belharra
  • Vaculuse
    • Avignon, Vaculuse, France
      • Institut Sainte Catherine
  • Val De Marne
    • Villejuif, Val De Marne, France
      • Institut Gustave Roussy
• Germany
  • Berlin, Germany
    • Vivantes Klinikum im Friedrichshain
  • Berlin, Germany
    • Vivantes Klinikum Spandau
  • Berlin, Germany
    • Evangelische Lungenklinik Berlin
  • Berlin, Germany
    • Vivantes Klinikum Neukoelln
  • Hamburg, Germany
    • Asklepios Klinik Harburg
  • Baden-Wurttemberg
    • Esslingen am Neckar, Baden-Wurttemberg, Germany
      • Klinikum Esslingen GmbH
    • Heidelberg, Baden-Wurttemberg, Germany
      • Thoraxklinik Heidelberg gGmbH
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany
      • Universitaetsmedizin Goettingen
    • Hanover, Lower Saxony, Germany
      • MHH Medizinische Hochschule Hannover
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany
      • Johannes Gutenberg University Mainz
  • Saxony
    • Dresden, Saxony, Germany
      • Universitätsklinikum Carl Gustav Carus Dresden
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany
      • MVZ Martha-Maria Halle-Doelau
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany
      • LungenClinic Grosshansdorf GmbH
• Greece
  • Athens, Greece
    • Alexandra General Hospital
  • Athens, Greece
    • University General Hospital Attikon
  • Athens, Greece
    • Henry Dunant Hospital Center
  • Heraklion, Greece
    • University General Hospital of Heraklion
  • Larissa, Greece
    • University General Hospital of Larissa
  • Thessaloniki, Greece
    • Interbalkan Hospital of Thessaloniki
  • Thessaloniki, Greece
    • Bioclinic Thessaloniki
• Hungary
  • Budapest, Hungary
    • Országos Korányi Pulmonológiai Intézet
  • Kecskemét, Hungary
    • Bács-Kiskun County Hospital BKMK
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St James's Hospital
  • Dublin, Ireland
    • St Vincent's University Hospital
  • Limerick, Ireland
    • University Hospital Limerick
  • Waterford, Ireland
    • Waterford Regional Hospital
• Italy
  • Bergamo, Italy
    • ASST Papa Giovanni XXIII
  • Candiolo, Italy
    • Istituto di Candiolo
  • Genova, Italy
    • Istituto Nazionale Per La Ricerca Sul Cancro Di Genova
  • Meldola, Italy
    • IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
  • Milan, Italy
    • IRCCS Istituto Nazionale dei Tumori
  • Ravenna, Italy
    • Ospedale Santa Maria delle Croci
  • Roma, Italy
    • Regina Elena National Cancer Institute
  • Verona, Italy
    • CRC - Centro Ricerche Cliniche di Verona S.r.l.
  • Milano
    • Monza, Milano, Italy
      • Fondazione IRCCS San Gerardo dei Tintori
    • Rozzano, Milano, Italy
      • Istituto Clinico Humanitas
  • Napoli
    • Naples, Napoli, Italy
      • AOU Università degli Studi della Campania "Luigi Vanvitelli"
  • Pordenone
    • Aviano, Pordenone, Italy
      • IRCCS Centro di Riferimento Oncologico
  • Roma
    • Rome, Roma, Italy
      • IRCCS Policlinico Universitario Agostino Gemelli
  • Torino
    • Orbassano, Torino, Italy
      • AOU San Luigi Gonzaga
• Japan
  • Bunkyō City, Japan
    • Nippon Medical School Hospital
  • Chūōku, Japan
    • National Cancer Center Hospital
  • Fukuoka, Japan
    • Nho Kyushu Cancer Center
  • Hokkaido, Japan
    • NHO Hokkaido Cancer Center
  • Kurashiki-shi, Japan
    • Kurashiki Central Hospital
  • Kurume-shi, Japan
    • Kurume University Hospital
  • Kōtō City, Japan
    • Cancer Institute Hospital of JFCR
  • Nagoya, Japan
    • Aichi Cancer Center Hospital
  • Nagoya, Japan
    • NHO Nagoya Medical Center
  • Natori-shi, Japan
    • Miyagi Cancer Center
  • Okayama, Japan
    • Okayama University Hospital
  • Osaka, Japan
    • Osaka International Cancer Institute
  • Osaka, Japan
    • Osaka Medical and Pharmaceutical University Hospital
  • Ota-shi, Japan
    • Gunma Prefectural Cancer Center
  • Yokohama, Japan
    • Kanagawa cancer center
  • Ehime
    • Matsuyama, Ehime, Japan
      • Shikoku Cancer Center
  • Fukuoka
    • Kitakyushu-shi, Fukuoka, Japan
      • JCHO Kyushu Hospital
  • Hiroshima
    • Hiroshima, Hiroshima, Japan
      • Hiroshima University Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan
      • Kobe Minimally Invasive Cancer Center
  • Kumamoto
    • Kumamoto, Kumamoto, Japan
      • Saiseikai Kumamoto Hospital
  • Osaka
    • Osakasayama-shi, Osaka, Japan
      • Kindai University Hospital
  • Tokyo-To
    • Bunkyō City, Tokyo-To, Japan
      • Juntendo University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek
  • Amsterdam, Netherlands
    • Amsterdam UMC Locatie VUMC
  • Harderwijk, Netherlands
    • St. Jansdal Ziekenhuis
  • Heerlen, Netherlands
    • Zuyderland Medisch Centrum - Heerlen
  • Leiden, Netherlands
    • Leiden University Medical Center
  • Nijmegen, Netherlands
    • Radboudumc
  • Rotterdam, Netherlands
    • Erasmus Medisch Centrum
  • Utrecht, Netherlands
    • Universitair Medisch Centrum Utrecht
  • Zwolle, Netherlands
    • Isala Zwolle
• Poland
  • Koszalin, Poland
    • Szpital Wojewodzki im. Mikolaja Kopernika w Koszalinie
  • Krakow, Poland
    • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
  • Lodz, Poland
    • Polish Mother's Memorial Hospital (Instytut Centrum Zdrowia Matki Polki)
  • Skorzewo, Poland
    • Aidport sp z o.o.
  • Warsaw, Poland
    • Instytut Gruzlicy i Chorob Pluc w Warszawie
  • Warsaw, Poland
    • Maria Sklodowska-Curie National Research Institute of Oncology (Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie)
• Portugal
  • Coimbra, Portugal
    • Unidade Local de Saude de Coimbra E P E
  • Matosinhos Municipality, Portugal
    • Unidade Local de Saúde de Matosinhos, E.P.E. - Hospital Pedro Hispano
  • Porto, Portugal
    • Hospital CUF Porto
  • Setúbal, Portugal
    • Unidade Local de Saude da Arrabida E. P. E
• Puerto Rico
  • San Juan, Puerto Rico, 902
    • Pan American Oncology Trials, LLC
  • San Juan, Puerto Rico, 917
    • Auxilio Mutuo Cancer Center
• South Korea
  • Cheongju-si, South Korea
    • Chungbuk National University Hospital
  • Daegu, South Korea
    • Keimyung University Dongsan Hospital
  • Goyang-si, South Korea
    • National Cancer Center Korea
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea
      • Ajou University Hospital
• Spain
  • Alicante, Spain
    • Hospital General Universitario Dr. Balmis
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Girona, Spain
    • ICO Girona
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain
    • Facility name: Clínica Universidad de Navarra
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Málaga, Spain
    • Hospital Quironsalud Malaga
  • Seville, Spain
    • Hospital Universitario Virgen Macarena
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain
    • IVO - Instituto Valenciano de Oncologia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain
      • ICO L'Hospitalet
  • Córdoba
    • Córdoba, Córdoba, Spain
      • Hospital Universitario Reina Sofia
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain
      • Complejo Hospitalario Universitario de Santiago CHUS
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain
      • Complejo Hospitalario Universitario Insular Materno-Infantil
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain
      • Hospital Universitario Quironsalud Madrid
  • Málaga
    • Marbella, Málaga, Spain
      • H.C. Hospitales S.L.
  • Navarre
    • Pamplona, Navarre, Spain
      • Clinica Universidad de Navarra
• Taiwan
  • Douliu, Taiwan
    • National Taiwan University Hospital Yunlin Branch
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Cancer Center
  • Taoyuan City, Taiwan
    • Chang Gung Memorial Hospital,Linkou
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye)
    • Adana City Hospital
  • Adana, Turkey (Türkiye)
    • Medical Park Seyhan Hospital
  • Ankara, Turkey (Türkiye)
    • Gulhane Training and Research Hospital
  • Ankara, Turkey (Türkiye)
    • Ankara City Hospital
  • Ankara, Turkey (Türkiye)
    • Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital
  • Ankara, Turkey (Türkiye)
    • Liv Hospital Ankara
  • Istanbul, Turkey (Türkiye)
    • Goztepe Prof. Dr. Suleyman Yalcin City Hospital
  • Istanbul, Turkey (Türkiye)
    • Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
  • Izmir, Turkey (Türkiye)
    • İ.E.Ü. Medicalpoint İzmir Hastanesi
• United Kingdom
  • London, United Kingdom
    • Guy'S Hospital
  • London, United Kingdom
    • Barts Hospital
  • Manchester, United Kingdom
    • The Christie Hospital
  • Nottingham, United Kingdom
    • Nottingham University Hospitals City Campus
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom
      • Beatson West of Scotland Cancer Care
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Arizona Blood and Cancer Specialists
  • California
    • Los Angeles, California, United States, 90089
      • Usc Norris Comprehensive Cancer Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Vallejo Medical Center
  • Florida
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center P.L.
    • Orlando, Florida, United States, 32806
      • Orlando Regional Medical Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute Atlanta
    • Atlanta, Georgia, United States, 30328
      • Piedmont Cancer Institute - Sandy Springs (Atlanta) Office
    • Fayetteville, Georgia, United States, 30214
      • Piedmont Cancer Institute - Fayetteville Office
    • Newnan, Georgia, United States, 30265
      • Piedmont Cancer Institute - Newnan Office
    • Stockbridge, Georgia, United States, 30281
      • Piedmont Cancer Institute - Stockbridge Office
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Kaiser Foundation Hospitals
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46219
      • Community Cancer Center East Medical Oncology Hematology
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
    • Pikeville, Kentucky, United States, 41501
      • Pikeville Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • St. Francis Hospital - Grand Island
    • Omaha, Nebraska, United States, 68124
      • Oncology Hematology West
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • New York
    • Stony Brook, New York, United States, 11790
      • Stony Brook University Medical Center|University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Pharmacy
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Oncology Specialists
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Parkridge Medical Center
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center Cancer Institute
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Midtown Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology-Austin Midtown
    • Austin, Texas, United States, 78731
      • Texas Oncology-Austin Central
    • Austin, Texas, United States, 78745
      • South Austin Cancer Ctr
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Hematology and Oncology
  • Washington
    • Seattle, Washington, United States, 98104
      • Cancer Institute At Swedish Med Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participant has histologically or cytologically confirmed locally advanced (unresectable stage IIIB/C) or metastatic NSCLC (stage IV) with known subtype.

• Participant has progressed radiographically on or after receiving:

  • One prior line of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy concomitantly) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting; OR
  • No more than 2 prior lines of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy sequentially, irrespective of the order) in the locally advanced (unresectable stage IIIB/C) or metastatic disease setting.
• Participant must have positive tumor PD-L1 expression (tumor cells ≥1%) determined prospectively on a tumor sample from the locally advanced (unresectable stage IIIB/C) or metastatic setting at a sponsor-designated central laboratory.
• Participant has measurable disease according to RECIST v1.1 as assessed by the investigator at baseline.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 7 days of Cycle 1 Day 1.
• Participant has a life expectancy of ≥3 months.
• Participant must have adequate organ and bone marrow function, per laboratory test results within 7 days of trial treatment.

Key Exclusion Criteria:

• Documentation of known targetable epidermal growth factor receptor (EGFR) sensitizing mutations, anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), ROS proto-oncogene 1; receptor tyrosine kinase (ROS1) rearrangement, Kirsten rat sarcoma virus (KRAS), B-Raf proto-oncogene (BRAF) mutations, and MET proto-oncogene; receptor tyrosine kinase (MET) exon 14 skipping mutations/MET amplification. NOTE: MET amplification testing is optional based on local availability of the test.

  • Participants with known KRAS/BRAF mutations are eligible for the trial if they do not have access to targeted therapies.
• Participants with newly identified, untreated or unstable or symptomatic central nervous system (CNS) metastases or history of carcinomatous meningitis.
• Prior treatment with docetaxel for NSCLC.
• Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor vaccine, autologous cell immunotherapy, or any unapproved immunotherapy.
• Treatment with an anticancer agent within 28 days prior to the first dose of trial treatment.

Note: Other protocol-defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Acasunlimab, 100 mg and pembrolizumab, 400 mg will be administered via intravenous (IV) infusion, once every 6 weeks (Q6W) (Cycle length=42 days).	Drug: Pembrolizumab; IV infusion; Drug: Acasunlimab; IV infusion; Other Names: DuoBody®-PD-L1×4-1BB; GEN1046
Active Comparator: Arm B; Docetaxel, 75 mg/m^2 will be administered via IV infusion, once every 3 weeks (Q3W) (Cycle length=21 days).	Drug: Docetaxel; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from date of randomization to date of death due to any cause.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause, whichever occurs first based on response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator.	Up to approximately 5 years
Confirmed Overall Response Rate (ORR)	Confirmed ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) based on RECIST v1.1 as assessed by the investigator.	Up to approximately 5 years
Duration of Response (DOR)	DOR is defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by the investigator.	Up to approximately 5 years
Number of Participants With Adverse Events (AEs)		From first dose until the end of the study (approximately 5 years)
Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The PRO-CTCAE allows participants to report on the frequency, severity, and interference of patient-reported symptoms. For each AE, there are between one and three items to assess the frequency, severity, and/or interference with activities related to that AE. All PRO-CTCAE responses will be scored from 0 to 4 for frequency indicating (0= never to 4= almost constantly), severity (0= none to 4= very severe) and interference with usual or daily activities (0= not at all to 4= very much).	Up to approximately 2 years
Time to Treatment Discontinuation Due to AE		From first dose until the end of the study (approximately 5 years)
Change From Baseline in Functional Assessment of Cancer Therapy Item GP5 (FACIT-GP5; Version 4) Score	Participant's global assessment of treatment tolerability will be assessed by FACIT-GP5. FACIT-GP5 asks participants to rate their agreement with the following statement, "I am bothered by side effects of treatment" in the past 7 days. Responses will be captured on a 5-point Likert scale ranging from 0 to 4 indicating 0 as not at all to 4 as very much bothered by side effects.	Baseline up to approximately 2 years
Plasma Concentration of Acasunlimab		Predose and postdose at multiple timepoints in Cycles 1-4 (Cycle length=42 days)
Number of Participants With Anti-drug Antibodies (ADAs) to Acasunlimab	Serum samples will be analyzed using validated, specific, and sensitive immunoassay method. Samples will be screened for ADAs binding to acasunlimab and the titer of confirmed positive/negative samples will be reported.	Predose and postdose at multiple timepoints in Cycles 1-4 (Cycle length=42 days)

Collaborators and Investigators

• Sponsor: Genmab
• Collaborators: BioNTech SE
• Investigators: Study Director: Study Official, Genmab

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Lung Cancer; PD-L1; Solid Tumors; 4-1BB
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; pembrolizumab
• Other Study ID Numbers: GCT1046-06; 2024-512998-27-00 (Ctis); jRCT2051240178 (Registry Identifier: Japan Registry of Clinical Trials); 1010602 (Registry Identifier: UK Research Summary Database); NL-OMON57246 (Registry Identifier: NL CCMO)

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