GEN1042 Safety Trial And Anti-tumor Activity In Participants With Malignant Solid Tumors

Study Overview

GEN1042 Safety Trial and Anti-tumor Activity in Participants 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.

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.

Malignant Solid Tumor
Non-Small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Melanoma
Head and Neck Squamous Cell Carcinoma (HNSCC)
Pancreatic Ductal Adenocarcinoma (PDAC)

BIOLOGICAL: GEN1042
DRUG: Pembrolizumab
DRUG: Cisplatin
DRUG: Carboplatin
DRUG: 5-FU
DRUG: Gemcitabine
DRUG: Nab paclitaxel
DRUG: Pemetrexed
DRUG: Paclitaxel

GCT1042-01
2018-003716-47 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )
IRAS ID: 263292 (REGISTRY Identifier) (REGISTRY: UK Research Summaries Database)
MOH_2023-07-31_012855 (REGISTRY Identifier) (REGISTRY: Israel MyTrials)
2023-508526-10 (OTHER Identifier) (OTHER: EU Trial (CTIS) Number)
RECF-005255 (OTHER Identifier) (OTHER: National Institute of Cancer France)
Rg13-835_03.08.2023 (OTHER Identifier) (OTHER: AMDM Moldova)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-09-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-02
First Submitted that Met QC Criteria 2019-09-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-03
First Posted (ACTUAL) 2019-09-10	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

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	BIOLOGICAL: GEN1042 Intravenous DRUG: Pembrolizumab Intravenous DRUG: Cisplatin Intravenous DRUG: Carboplatin Intravenous DRUG: 5-FU Intravenous DRUG: Gemcitabine Intravenous DRUG: Nab paclitaxel Intravenous DRUG: Pemetrexed Intravenous DRUG: Paclitaxel Intravenous

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

BIOLOGICAL: GEN1042

Intravenous

DRUG: Pembrolizumab

Intravenous

DRUG: Cisplatin

Intravenous

DRUG: Carboplatin

Intravenous

DRUG: 5-FU

Intravenous

DRUG: Gemcitabine

Intravenous

DRUG: Nab paclitaxel

Intravenous

DRUG: Pemetrexed

Intravenous

DRUG: Paclitaxel

Intravenous

Primary Outcome Measures	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 3 years

Secondary Outcome Measures	Measure Description	Time Frame
All Parts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)		From first dose until the end of the study (approximately 3 years)
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 3 years
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 3 years
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 3 years
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 3 years
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 3 years
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)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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.

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

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

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

BioNTech SE

Investigators

STUDY_DIRECTOR: Study Official, Genmab

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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.

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