GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Non-Small Cell Lung Cancer (NSCLC); Malignant Solid Tumor; Pancreatic Ductal Adenocarcinoma (PDAC); Head and Neck Squamous Cell Carcinoma (HNSCC); Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pembrolizumab; Drug: Pemetrexed; Biological: GEN1042; Drug: 5-FU; Drug: Nab paclitaxel

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 2 years and 4 months.
• 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.

A long-term extension phase (LTEP) has been added to allow continued access to trial treatment for up to 2 years from the individual participant's Cycle 1 Day 1 visit.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet (Copenhagen University Hospital)
  • Herlev, Denmark
    • Herlev University Hospital
  • Vejle, Denmark
    • University Hospital of Southern Denmark, Vejle Hospital
• France
  • Bordeaux, France
    • Centre Hospitalier Universitaire De Bordeaux
  • Nice, France
    • Centre Antoine Lacassagne
  • Villejuif, France
    • Gustave Roussy
• Georgia
  • Tbilisi, Georgia
    • ARENSIA Research Clinic at the Research Institute of Clinical Medicine
• Germany
  • Heidelberg, Germany
    • Nationales Centrum fr Tumorerkrankungen NCT
  • Ludwigshafen, Germany
    • Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • Mainz, Germany
    • Department of Dermatology, University of Mainz
  • Mannheim, Germany
    • Universitätsmedizin Mannheim Dermatologie
  • Würzburg, Germany
    • Universitaetsklinikum Wuerzburg
• Israel
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Brescia, Italy
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Cuneo, Italy
    • Azienda Ospedaliera S.Croce e Carle Cuneo
  • Milan, Italy
    • Istituto Nazionale dei Tumori
  • Rozzano, Italy
    • Istituto Clinico Humanitas
• Moldova
  • Chisinau, Moldova
    • ARENSIA Research Clinic at the Oncology Institute
• South Korea
  • Cheongju-si, South Korea
    • Chungbuk National University Hospital
  • Jeonju, South Korea
    • Jeonbuk National University Hospital
  • Namdong, South Korea
    • Gachon University Gil Medical Center
  • Seoul, South Korea
    • Korea University Guro Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
  • Yangsan, South Korea
    • Pusan National University Yangsan Hospital
• Spain
  • Barcelona, Spain
    • H. Vall D'Hebron
  • Barcelona, Spain
    • START Barcelona HM Nou Delfos
  • L'Hospitalet de Llobregat, Spain
    • Hospital Duran i Reynals - ICO L Hospitalet
  • Las Palmas de Gran Canaria, Spain, 35016
    • Hospital Universitario Insular de Gran Canaria
  • Lugo, Spain
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • MD Anderson Cancer Center Madrid
  • Madrid, Spain
    • Clinica Universidad de Navarra
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maran
  • Madrid, Spain
    • HM CIOCC Hospital Universitario HM Sanchinarro
  • Madrid, Spain
    • START Madrid - Hospital Universitario Fundación Jiménez Díaz
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Pamplona, Spain
    • Clinica Universidad de Navarra
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Seville, Spain
    • Hospital Virgen Del Rocio
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia
• Taiwan
  • Kaohsiung City, Taiwan
    • Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Taipei Medical University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital, VGHTPE
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital Linkou Branch
• United Kingdom
  • Sutton, United Kingdom
    • Royal Marsden NHS Foundation Trust
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
  • California
    • Los Alamitos, California, United States, 90720
      • Cancer & Blood Specialty Clinic
    • San Diego, California, United States, 92037
      • Moores Cancer Center at the UC San Diego Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • ChristianaCare
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Comprehensive Cancer Center
    • Ocala, Florida, United States, 34474
      • Florida Cancer Affiliates
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Hope and Healing Cancer Services
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology PA
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Cancer Institute - Forsyth (Medical Oncology)
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente (KP) Oncology/Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Kingwood, Texas, United States, 77339
      • LUMI Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Utah Cancer Specialists
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virgina Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Adventist Health System/Sunbelt,Inc
    • Spokane, Washington, United States, 99204
      • Medical Oncology Associates, PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy - Dose Escalation and Dose Expansion Parts	Biological: GEN1042; Intravenous
Experimental: Combination Therapy - Safety Run-in and Expansion Parts	Drug: Carboplatin; Intravenous; Drug: Paclitaxel; Intravenous; Drug: Cisplatin; Intravenous; Drug: Gemcitabine; Intravenous; Drug: Pembrolizumab; Intravenous; Drug: Pemetrexed; Intravenous; Biological: GEN1042; Intravenous; Drug: 5-FU; Intravenous; Drug: Nab paclitaxel; Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation and Safety Run-in Parts: Number of Participants With Dose-Limiting Toxicities (DLTs)	Toxicities will be graded for severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0	First Cycle (21 days)
Dose Expansion: Objective Response Rate (ORR)	ORR is defined as the percentage of participants with best overall response (BOR) [complete or partial response (PR or CR)] based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator.	Up to approximately 2 years and 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Parts: Area Under the Concentration-Time Curve (AUC) of GEN1042		Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1042		Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Half-life (t½) of GEN1042		Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Number of Participants With Anti-drug Antibody (ADA) Response to GEN1042	Serum samples will be screened for antibodies binding to GEN1042 and the titer of confirmed positive samples will be reported.	Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		From first dose until the end of the study (approximately 2 years and 4 months)
Dose Escalation: ORR	ORR is defined as the percentage of participants with BOR (PR or CR) based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 2 years and 4 months
All Parts: Duration of Objective Response (DOR)	DOR is defined as time from the first documentation of objective tumor response (CR or PR) to the date of first progressive disease (PD) or death based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 2 years and 4 months
All Parts: Disease Control Rate (DCR)	DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 2 years and 4 months
All Parts: Progression-Free Survival (PFS)	PFS is defined as the time from Day 1 in Cycle 1 to the first documented progression or death due to any cause based on RECIST version 1.1 as assessed by the investigator.	Up to approximately 2 years and 4 months
All Parts: Overall Survival (OS)	OS is defined as time from Day 1 in Cycle 1 to death due to any cause.	Up to approximately 2 years and 4 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• Bajaj G, Shchelokov D, Demin O Jr, Adams HC 3rd, Feng Y, Gibiansky L, van der Lee S, Johri A, Belete M, Muik A, Panorchan P, Tureci O, Sahin U, Ahmadi T, Gupta M, Demin O, Thalhauser C. Dose Selection for DuoBody(R)-CD40x4-1BB (GEN1042/BNT312) Using a mPBPK/RO Model Leveraging Preclinical and Clinical Data. Clin Pharmacol Ther. 2025 Aug;118(2):418-427. doi: 10.1002/cpt.3677. Epub 2025 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Actual): December 30, 2025
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Health Care Economics and Organizations; Uracil; Pyrimidinones; Platinum Compounds; Economics; Pemetrexed; Gemcitabine; Fluorouracil; Carboplatin; Paclitaxel; Cisplatin; pembrolizumab; Taxes
• Other Study ID Numbers: GCT1042-01; 2018-003716-47 (EudraCT Number); IRAS ID: 263292 (Registry Identifier: UK Research Summaries Database); MOH_2023-07-31_012855 (Registry Identifier: Israel MyTrials); 2023-508526-10-00 (Ctis: EU CT Number); 2023-508526-10 (Other Identifier: EU Trial (CTIS) Number); RECF-005255 (Other Identifier: National Institute of Cancer France); Rg13-835_03.08.2023 (Other Identifier: AMDM Moldova); 1129008831 (Registry Identifier: Taiwan Food and Drug Administration)

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