Malignant Solid TumorPhase 1/2NCT04083599
GEN1042 Safety Trial and Anti-tumor Activity in Participants With Malignant Solid Tumors
A Phase 1/2 study testing GEN1042, Pembrolizumab and Cisplatin in people with Malignant Solid Tumor and Non-Small Cell Lung Cancer (NSCLC), run by Genmab at 76 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Solid Tumor, Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC)
- What is being tested?
- GEN1042, Pembrolizumab and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 76 sitesin 12 countries
- Study dates
- 17 Sep 2019to Jan 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
76 sites in 12 countries.
76 sites in 12 countries
United States23 sites
Alaska Oncology and Hematology LLC
Anchorage, Alaska, 99508
Levine Cancer Center
Charlotte, North Carolina, 28204
Maryland Oncology Hematology PA
Columbia, Maryland, 21044
Virgina Cancer Specialists
Fairfax, Virginia, 22031
Hope and Healing Cancer Services
Hinsdale, Illinois, 60521
Lumi Research
Kingwood, Texas, 77339
University of Kentucky
Lexington, Kentucky, 40536
Cancer & Blood Specialty Clinic
Los Alamitos, California, 90720
Norton Cancer Institute
Louisville, Kentucky, 40202
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Yale University Cancer Center
New Haven, Connecticut, 06520
ChristianaCare
Newark, Delaware, 19713
Florida Cancer Affiliates
Ocala, Florida, 34474
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Kaiser Permanente (KP) Oncology/Hematology
Portland, Oregon, 97227
Utah Cancer Specialists
Salt Lake City, Utah, 84124
Moores Cancer Center at the UC San Diego Health
San Diego, California, 92037
Adventist Health System/Sunbelt,Inc
Seattle, Washington, 98109
Medical Oncology Associates, PS
Spokane, Washington, 99204
Washington University School of Medicine
St Louis, Missouri, 63110
Novant Health Cancer Institute - Forsyth (Medical Oncology)
Winston-Salem, North Carolina, 27103
Spain19 sites
H. Vall d'Hebron
Barcelona
START Barcelona HM Nou Delfos
Barcelona
Hospital Duran i Reynals - ICO L Hospitalet
L'Hospitalet de Llobregat
Hospital Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria, 35016
Hospital Universitario Lucus Augusti
Lugo
Clinica Universidad de Navarra
Madrid
HM CIOCC Hospital Universitario HM Sanchinarro
Madrid
Hospital Clinico San Carlos
Madrid
Hospital General Universitario Gregorio Maran
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario La Paz
Madrid
Hospital Universitario Ramon y Cajal
Madrid
MD Anderson Cancer Center Madrid
Madrid
START Madrid - Hospital Universitario Fundacion Jimenez Diaz
Madrid
Hospital Universitario Virgen de la Victoria
Málaga
Clinica Universidad de Navarra
Pamplona
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela
Hospital Virgen del Rocio
Seville
Hospital Clinico Universitario de Valencia
Valencia
South Korea7 sites
Chungbuk National University Hospital
Cheongju-si
Jeonbuk National University Hospital
Jeonju
Gachon University Gil Medical Center
Namdong
Korea University Guro Hospital
Seoul
Samsung Medical Center
Seoul
Severance Hospital, Yonsei University Health System
Seoul
Pusan National University Yangsan Hospital
Yangsan
Taiwan7 sites
Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch
Kaohsiung City
Kaohsiung Medical University Memorial Hospital
Kaohsiung City
China Medical University Hospital
Taichung
National Cheng Kung University Hospital
Tainan
Taipei Medical University Hospital
Taipei
Taipei Veterans General Hospital, VGHTPE
Taipei
Chang Gung Memorial Hospital Linkou Branch
Taoyuan
Germany5 sites
Nationales Centrum fr Tumorerkrankungen NCT
Heidelberg
Klinikum der Stadt Ludwigshafen am Rhein gGmbH
Ludwigshafen
Department of Dermatology, University of Mainz
Mainz
Universitätsmedizin Mannheim Dermatologie
Mannheim
Universitaetsklinikum Wuerzburg
Würzburg
Italy4 sites
Azienda Ospedaliera Spedali Civili di Brescia
Brescia
Azienda Ospedaliera S.Croce e Carle Cuneo
Cuneo
Istituto Nazionale dei Tumori
Milan
Istituto Clinico Humanitas
Rozzano
Denmark3 sites
Rigshospitalet (Copenhagen University Hospital)
Copenhagen
Herlev University Hospital
Herlev
University Hospital of Southern Denmark, Vejle Hospital
Vejle
France3 sites
Centre hospitalier Universitaire de Bordeaux
Bordeaux
Centre Antoine Lacassagne
Nice
Gustave Roussy
Villejuif
Israel2 sites
Rabin Medical Center
Petah Tikva
Tel Aviv Sourasky Medical Center
Tel Aviv
Georgia1 site
ARENSIA Research Clinic at the Research Institute of Clinical Medicine
Tbilisi
About this study
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
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.
Read the 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.
- 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)
- Being tested
- GEN1042, Pembrolizumab, Cisplatin, Carboplatin, 5-FU
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Melanoma, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GEN1042Biological
Intravenous
PembrolizumabDrug
Intravenous
CisplatinDrug
Intravenous
CarboplatinDrug
Intravenous
5-FUDrug
Intravenous
GemcitabineDrug
Intravenous
Nab paclitaxelDrug
Intravenous
PemetrexedDrug
Intravenous
PaclitaxelDrug
Intravenous
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy - Dose Escalation and Dose Expansion Parts | Experimental | Not described Receives: Biological: GEN1042 |
| Combination Therapy - Safety Run-in and Expansion Parts | Experimental | Not described Receives: Biological: GEN1042; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-FU; Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Up to approximately 2 years and 4 months
Secondary outcomes (10)
All Parts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to approximately 2 years and 4 months
All Parts: Area Under the Concentration-Time Curve (AUC) of GEN1042
Measured: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Maximum Observed Plasma Concentration (Cmax) of GEN1042
Measured: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
All Parts: Half-life (t½) of GEN1042
Measured: 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.
Measured: Predose and postdose at multiple timepoints up to end of treatment (approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start17 Sep 2019
- Primary completion30 Dec 2025
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malignant Solid TumorStudies of the same condition, open and under way.
- More trials run by GenmabThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genmab
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- BioNTech SE
- Responsible party
- Sponsor
- Investigators
- Study Official, Study director, Genmab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083599
- Sponsor's protocol ID
- GCT1042-01
- Other IDs
- 2018-003716-47, IRAS ID: 263292, MOH_2023-07-31_012855, 2023-508526-10, RECF-005255, Rg13-835_03.08.2023, 2023-508526-10-00, 1129008831
- Status last verified
- Aug 2026
- First submitted
- 6 Sep 2019
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40347227Muik 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.
PubMed 35688554