Clinical trial NCT05117242: Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer
Official title: A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination Pembrolizumab Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer Metastatic
Keywords: DuoBody®
Bispecific antibody
PD-L1
4-1BB
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-11-11
Enrollment: 125
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: 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.


Eligibility criteria: Key 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.

Key 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: From first treatment to approximately 27 weeks after last subject's first dose
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: 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)
measure: Time to response (TTR)
timeFrame: 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)
measure: Progression-free survival (PFS)
timeFrame: From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
measure: Overall survival (OS)
timeFrame: From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
measure: Incidence and severity of adverse events (AEs) and laboratory abnormalities
timeFrame: Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - FCS South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Center
state: Florida
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan CHCWM P.C.
state: Michigan
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: Hopital Morvan CHU de Brest
city: Rouen
country: France
facility: Hopital Charles Nicolle Chu Rouen
city: St Mande
country: France
facility: Hopital dInstruction Des Armees Begin
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe (ICANS)
city: Suresnes
country: France
facility: Hôpital Foch
city: Villejuif
country: France
facility: Gustave Roussy
city: Frankfurt am main
country: Germany
facility: IKF Krankenhaus Nordwest
city: Hanover
country: Germany
facility: Med.Hochschule Hannover Klinik für Pneumologie
city: Hessen
country: Germany
facility: Universitatsklinik Giessen und Marburg Standort Giessen
city: Immenhausen
country: Germany
facility: LKI Lungenfachklinik Immenhausen
city: Regensburg
country: Germany
facility: Department of Internal Medicine II
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco
city: Genova
country: Italy
facility: ASL 3 Genovese Ospedale Villa Scassi
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: UOC Oncoematologia AOU L.Vanvitelli
city: Palermo
country: Italy
facility: La Maddalena SPA
city: Ravenna
country: Italy
facility: AUSL della Romagna
city: Roma
country: Italy
facility: IFO Regina Elena
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
city: Poznań
country: Poland
facility: Med Polonia Sp. z o.o.
city: Prabuty
country: Poland
facility: Szpital Specjalistyczny w Prabutach Sp. z o.o.
city: Warszawa
country: Poland
facility: Maria Sklodowska-Curie National Research Institute of Oncology
city: Braga
country: Portugal
facility: Clinical Academic Center Braga
city: Lisbon
country: Portugal
facility: Centro Clinico Champalimaud
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologio de Lisboa
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio
city: Barcelona
country: Spain
facility: Hospital Universitari Vall dHebron
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra CUN
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: The Christie Hospital
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: