Clinical trial NCT04083599: GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors
Official title: A First-in-Human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Solid Tumor
Non-Small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Melanoma
Head and Neck Squamous Cell Carcinoma (HNSCC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2019-09-10
Enrollment: 1287
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this trial is to learn about the antibody GEN1042 when it is used alone and when it is used together with another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of participants with certain types of cancer.

Detailed description: This is an open-label, multicenter phase 1/2 study designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of GEN1042 administered as a monotherapy or in combination in participants with metastatic or locally advanced solid tumors.

Participants will receive either GEN1042 alone, GEN1042 with pembrolizumab, or GEN1042 with pembrolizumab and chemotherapy. All participants will receive active drug; no one will receive placebo.

This trial has 2 parts. The purpose of the first part is to find out if GEN1042 is safe and to find out the best doses of GEN1042 to use. The purpose of the second part is to give GEN1042 to more participants to see how well the dose(s) of GEN1042 selected in the first part work against cancer with GEN1042 when given alone or in combination with pembrolizumab or in combination with pembrolizumab and chemotherapy.

Trial details include:

* The average trial duration will be about 3 years.
* The treatment duration will be up to 2 years (when GEN1042 is combined with pembrolizumab).
* 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:

Monotherapy - Dose Escalation and Dose Expansion Parts

* Participants with non-CNS solid tumors that is metastatic or unresectable and for whom there is no available standard therapy.
* Participants with a confirmed diagnosis of relapsed or refractory, advanced and/or metastatic melanoma, NSCLC, or CRC and for whom there is no available standard therapy

Combination Therapy - Dose Expansion Part

* Participants with unresectable Stage III or Stage IV melanoma with no prior systemic anticancer therapy for unresectable or metastatic disease. Primary ocular or mucosal melanoma is excluded.
* Participants with Stage IV metastatic or recurrent NSCLC with no prior systemic anticancer therapy, no actionable mutation.
* Participants with recurrent or metastatic HNSCC with no prior systemic therapy administered in the recurrent or metastatic setting.
* Participants with confirmed metastatic PDAC with no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.

General (all phases):

* Must be age ≥ 18 years of age on the day of signing informed consent, or the legal age of consent in the jurisdiction in which the trial is taking place.
* Measurable disease according to RECIST 1.1
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Normal or adequate liver, renal, cardiac and bone marrow function

Key Exclusion Criteria:

Monotherapy - Dose Escalation and Dose Expansion Parts

* Treatment with an anti-cancer agent (within 21 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1042 administration
* Radiotherapy within 14 days prior to first GEN1042 administration
* Toxicities from previous anti-cancer therapies that have not resolved

Combination Therapy - Dose Expansion Part

* Has received prior systemic cytotoxic chemotherapy, biological therapy, OR major surgery within 3 weeks or at least 5 half-lives of the drug (whichever is shorter) of the first dose of trial treatment.
* Radiotherapy within 14 days of start of trial treatment or received lung radiation therapy of \> 30 Gy within 6 months of the first dose of trial treatment.

General (all phases)

* Participants has an active, known, or suspected autoimmune disease.
* History of non-infectious pneumonitis that required steroids or currently has pneumonitis.
* History of ≥ grade 3 allergic reactions to monoclonal antibody (mAb) therapy
* Participants with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment.

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

Primary outcomes:
measure: Dose Escalation and Safety Run-in Parts: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: First Cycle (21 days)
measure: Dose Expansion: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: All Parts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose until the end of the study (approximately 3 years)
measure: Dose Escalation: ORR
timeFrame: Up to approximately 3 years
measure: All Parts: Duration of Objective Response (DOR)
timeFrame: Up to approximately 3 years
measure: All Parts: Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years
measure: All Parts: Progression-Free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: All Parts: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: All Parts: Area Under the Concentration-Time Curve (AUC) of GEN1042
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
measure: All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1042
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
measure: All Parts: Half-life (t½) of GEN1042
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
measure: All Parts: Number of Participants With Anti-drug Antibody (ADA) Response to GEN1042
timeFrame: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology LLC
state: Alaska
city: Los Alamitos
country: United States
facility: Cancer & Blood Specialty Clinic
state: California
city: San Diego
country: United States
facility: Moores Cancer Center at the UC San Diego Health
state: California
city: New Haven
country: United States
facility: Yale University Cancer Center
state: Connecticut
city: Newark
country: United States
facility: ChristianaCare
state: Delaware
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Affiliates
state: Florida
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Services
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Columbia
country: United States
facility: Maryland Oncology Hematology PA
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Charlotte
country: United States
facility: Levine Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Cancer Institute - Forsyth (Medical Oncology)
state: North Carolina
city: Portland
country: United States
facility: Kaiser Permanente (KP) Oncology/Hematology
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Virgina Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Adventist Health System/Sunbelt,Inc
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Copenhagen
country: Denmark
facility: Rigshospitalet (Copenhagen University Hospital)
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Vejle
country: Denmark
facility: University Hospital of Southern Denmark, Vejle Hospital
city: Bordeaux
country: France
facility: Centre hospitalier Universitaire de Bordeaux
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Villejuif
country: France
facility: Gustave Roussy
city: Tbilisi
country: Georgia
facility: ARENSIA Research Clinic at the Research Institute of Clinical Medicine
city: Heidelberg
country: Germany
facility: Nationales Centrum fr Tumorerkrankungen NCT
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: Mainz
country: Germany
facility: Department of Dermatology, University of Mainz
city: Mannheim
country: Germany
facility: UniversitÃ¤tsmedizin Mannheim Dermatologie
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S.Croce e Carle Cuneo
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Namdong
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Chisinau
country: Moldova, Republic of
facility: ARENSIA Research Clinic at the Oncology Institute
city: Barcelona
country: Spain
facility: H. Vall d'Hebron
city: Barcelona
country: Spain
facility: START Barcelona HM Nou Delfos
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Duran i Reynals - ICO L Hospitalet
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: HM CIOCC Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maran
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: START Madrid - Hospital Universitario Fundacion Jimenez Diaz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital, VGHTPE
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital Linkou Branch
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References:
citation: Muik A, Adams 3rd HC, Gieseke F, Altintas I, Schoedel KB, Blum JM, Sanger B, Burm SM, Stanganello E, Verzijl D, Spires VM, Vascotto F, Toker A, Quinkhardt J, Fereshteh M, Diken M, Satijn DPE, Kreiter S, Ahmadi T, Breij ECW, Tureci O, Sasser K, Sahin U, Jure-Kunkel M. DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. J Immunother Cancer. 2022 Jun;10(6):e004322. doi: 10.1136/jitc-2021-004322.