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

Non Small Cell Lung Cancer Metastatic Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05117242
• Other study ID #: GCT1046-04
• Secondary ID: 2021-001928-1710
• Status: Recruiting
• Phase: Phase 2
• Start date: October 27, 2021
• Est. completion date: March 2027

Study information

• Verified date: April 2024
• Source: Genmab
• Contact: Genmab A/S Trial Information
• Phone: +45 70202728
• Email: clinicaltrials[@]genmab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to investigate the safety and efficacy of acasunlimab (also known as GEN1046) as monotherapy and in combination with pembrolizumab in patients with non-small cell lung cancer who have progressed during or after treatment of previous standard of care

Description:

This trial is a randomized, open-label trial evaluating the safety and efficacy of acasunlimab (GEN1046) as monotherapy and in combination therapy with pembrolizumab. The trial consists of two parts; a safety phase and an extension phase. The extension phase will be initiated once the safety phase is completed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 2027
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 for the treatment of stage 4 NSCLC.
• 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer Metastatic

Intervention

Biological:
• Acasunlimab
Acasunlimab will be administered intravenously (IV)
• Pembrolizumab
Pembrolizumab will be administered IV

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Hopital Morvan CHU de Brest	Brest
France	Hopital Charles Nicolle Chu Rouen	Rouen
France	Hopital dInstruction Des Armees Begin	St Mande
France	Institut de Cancerologie Strasbourg Europe (ICANS)	Strasbourg
France	Hôpital Foch	Suresnes
France	Gustave Roussy	Villejuif
Germany	IKF Krankenhaus Nordwest	Frankfurt am main
Germany	Med.Hochschule Hannover Klinik für Pneumologie	Hanover
Germany	Universitatsklinik Giessen und Marburg Standort Giessen	Hessen
Germany	LKI Lungenfachklinik Immenhausen	Immenhausen
Germany	Department of Internal Medicine II	Regensburg
Italy	Azienda Ospedaliera Universitaria Policlinico G Rodolico San Marco	Catania
Italy	ASL 3 Genovese Ospedale Villa Scassi	Genova
Italy	IRCCS Istituto Europeo di Oncologia	Milano
Italy	UOC Oncoematologia AOU L.Vanvitelli	Napoli
Italy	La Maddalena SPA	Palermo
Italy	AUSL della Romagna	Ravenna
Italy	IFO Regina Elena	Roma
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	VU University Medical Center	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Erasmus MC	Rotterdam
Poland	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc	Olsztyn
Poland	Med Polonia Sp. z o.o.	Poznan
Poland	Szpital Specjalistyczny w Prabutach Sp. z o.o.	Prabuty
Poland	Maria Sklodowska-Curie National Research Institute of Oncology	Warszawa
Portugal	Clinical Academic Center Braga	Braga
Portugal	Centro Clinico Champalimaud	Lisbon
Portugal	Instituto Portugues de Oncologio de Lisboa	Lisbon
Portugal	Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio	Porto
Spain	Hospital Universitari Vall dHebron	Barcelona
Spain	Clinica Universidad de Navarra CUN	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	King's College London, Guy's Hospital	London
United Kingdom	University College London	London
United Kingdom	The Christie Hospital	Manchester
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	Florida Cancer Specialists - FCS South	Fort Myers	Florida
United States	Cancer & Hematology Centers of Western Michigan CHCWM P.C.	Grand Rapids	Michigan
United States	Penn State Cancer Institute Penn State Health Herhsey Medical Center	Hershey	Pennsylvania
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Florida Cancer Center	Saint Petersburg	Florida
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Oncology Clinical Trials Ascension Providence Hospital	Southfield	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Genmab	BioNTech SE, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of response (DOR)	DOR will be measured as the time from initial onset of CR or PR to first radiographic progression as per RECIST v. 1.1 or death from any cause, whichever occurs first.	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)
Secondary	Time to response (TTR)	TTR will be measured as the time from first treatment to onset of initial response (CR or PR) as per RECIST v.1.1	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)
Secondary	Progression-free survival (PFS)	PFS will be measured from date of first treatment until date of radiographic progression as per RECIST v.1.1 or until death from any cause, whichever occurs first	From first treatment to first documented progression or death due to any cause (an expected average of 6 months)
Secondary	Overall survival (OS)	Defined as time to death from of any cause	From first treatment to date of death (assessed up to 3 years after the last participant's first dose in the trial)
Secondary	Incidence and severity of adverse events (AEs) and laboratory abnormalities	Incidence of treatment-emergent AEs as assessed by CTCAE v5.0. Laboratory parameters graded by CTCAE v5.0	Throughout the trial until end of safety follow-up period (60 days or 90 days after last dose)