Clinical trial NCT06635824: Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: PD-L1-positive Metastatic NSCLC
Keywords: Lung Cancer
Solid Tumors
PD-L1
4-1BB
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2024-10-10
Enrollment: 702
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 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 metastatic setting.

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 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.

Eligibility criteria: Key Inclusion Criteria:

* Participant has histologically or cytologically confirmed 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 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 metastatic disease setting.
* Participant must have positive tumor PD-L1 expression (tumor cells ≥1%) determined prospectively on a tumor sample from the 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 approved targeted therapies.
* Participants with newly identified or known 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 5 years
measure: Confirmed Overall Response Rate (ORR)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 5 years
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose until the end of the study (approximately 5 years)
measure: Time to Treatment Discontinuation Due to AE
timeFrame: From first dose until the end of the study (approximately 5 years)
measure: Plasma Concentration of Acasunlimab
timeFrame: Predose and postdose at multiple timepoints in Cycles 1-4, then every other cycle starting Cycle 5 (Cycle length=42 days), up to approximately 5 years
measure: Number of Participants With Anti-drug Antibodies (ADAs) to Acasunlimab
timeFrame: Up to approximately 5 years
measure: Change From Baseline in Functional Assessment of Cancer Therapy Item GP5 (FACIT-GP5; Version 4) Score
timeFrame: Baseline up to approximately 2 years
measure: Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center
state: California
city: Ocala
country: United States
facility: Ocala Oncology Center P.L.
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Medical Center
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Cancer Institute Atlanta
state: Georgia
city: Honolulu
country: United States
facility: Kaiser Foundation Hospitals
state: Hawaii
city: Indianapolis
country: United States
facility: Community Cancer Center East Medical Oncology Hematology
state: Indiana
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Pikeville
country: United States
facility: Pikeville Medical Center
state: Kentucky
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West
state: Nebraska
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Midtown Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: La Rioja
country: Argentina
facility: Investigaciones CORI S.R.L.
city: Camperdown
country: Australia
facility: Chris OBrien LifeHouse
state: New South Wales
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
city: Wendouree
country: Australia
facility: Ballarat Oncology & Haematology Service
city: Linz
country: Austria
facility: Kepler Universitatsklinikum Med Campus III
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: C. H. U. St-Pierre
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Bruxelles
city: Gilly
country: Belgium
facility: Grand Hôpital de Charleroi
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
city: Roeselare
country: Belgium
facility: AZ Delta
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Ijuí
country: Brazil
facility: Hospital de Clinicas de Ijui
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
state: Rio Grande Do Su
city: São Paulo
country: Brazil
facility: BP A Beneficencia Portuguesa de Sao Paulo
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Centro Paulista de Oncologia S.A.
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Sirio-Libanes
state: Sao Paulo
city: Belo Horizonte
country: Brazil
facility: Oncoclínicas do Brasil Serviços Médicos SA
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Rio de Janeiro
country: Brazil
facility: Oncoclínicas Rio de Janeiro
city: Santo Andre
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: Pleven
country: Bulgaria
facility: MHAT Heart and Brain - Pleven
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv, EOOD
city: Sofia
country: Bulgaria
facility: MHAT "Serdika", EOOD
city: Sofia
country: Bulgaria
facility: MHAT for women's health - Nadezhda, OOD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: UMHAT 'SofiaMed', OOD
city: Providencia
country: Chile
facility: FALP - Fundación Arturo López Pérez
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica Bradford Hill
city: Santiago
country: Chile
facility: IRAM - Instituto de Radio Medicina
city: Vina del Mar
country: Chile
facility: Oncocentro APYS
city: Dubrovnik
country: Croatia
facility: General Hospital Dubrovnik
city: Rijeka
country: Croatia
facility: Specialty Hospital Medico
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Avignon Cedex 9
country: France
facility: Institut Sainte Catherine
state: Vaculuse
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
state: Val De Marne
city: Angers
country: France
facility: CHU Angers - Hôpital Larrey
city: Bayonne
country: France
facility: Centre Hospitalier de la côte Basque
city: Boulogne Billancourt
country: France
facility: Hôpital Ambroise Paré
city: Creteil Cedex
country: France
facility: Centre Hospitalier Intercommunal de Creteil (CHIC)
city: Lille Cedex
country: France
facility: Hopital Albert Calmette - CHU Lille
city: Lyon Cedex
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Assistance Publique-Hôpitaux de Marseille
city: Mulhouse
country: France
facility: CH de Mulhouse - Hôpital Emile Muller
city: Nantes
country: France
facility: Hôpital Privé du Confluent
city: Paris
country: France
facility: Hopital Saint Joseph - Paris
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Athens
country: Greece
facility: Henry Dunant Hospital Center
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki
city: Thessaloniki
country: Greece
facility: Interbalkan Hospital of Thessaloniki
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
state: Milano
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
state: Torino
city: Candiolo
country: Italy
facility: Istituto di Candiolo
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro di Genova
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Verona
country: Italy
facility: CRC - Centro Ricerche Cliniche di Verona S.r.l.
city: Matsuyama-shi
country: Japan
facility: Shikoku Cancer Center
state: Ehime-Ken
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
state: Osaka-Fu
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Cancer Center
city: Hokkaido
country: Japan
facility: NHO Hokkaido Cancer Center
city: Koto City
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Kurashiki-shi
country: Japan
facility: Kurashiki Central Hospital
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Nagoya
country: Japan
facility: NHO Nagoya Medical Center
city: Natori-shi
country: Japan
facility: Miyagi Cancer Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Osaka
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
city: Ota-shi
country: Japan
facility: Gunma Prefectural Cancer Center
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Locatie VUMC
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Harderwijk
country: Netherlands
facility: St. Jansdal Ziekenhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Zwolle
country: Netherlands
facility: Isala Zwolle
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
city: Lodz
country: Poland
facility: Polish Mother's Memorial Hospital (Instytut Centrum Zdrowia Matki Polki)
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc w Warszawie
city: San Juan
country: Puerto Rico
facility: Pan American Oncology Trials, LLC
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Córdoba
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Marbella
country: Spain
facility: H.C. Hospitales S.L.
state: Málaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Girona
country: Spain
facility: ICO Girona
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Quironsalud Malaga
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital Yunlin Branch
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital,Linkou
city: London
country: United Kingdom
facility: Barts Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals City Campus
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: