GEN1047 for Solid Tumors - First in Human (FIH) Trial

First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1047 in Subjects With Malignant Solid Tumors

The purpose of this trial is to measure the following in participants with solid tumors who receive GEN1047:

• The side effects seen with GEN1047
• What the body does with GEN1047 once it is administered
• What GEN1047 does to the body once it is administered
• How well GEN1047 works against solid tumors

The estimated trial duration for an individual participant is 8 months, consisting of a 28-day screening period, an estimated 3 month treatment period (the duration of treatment may vary for each participant), and an estimated 4 month post-treatment follow-up period (the duration of follow-up may vary for each participant). All participants will receive active drug; no one will be given placebo.

Study Overview

• Status: Terminated
• Conditions: Squamous Non Small Cell Lung Cancer (NSCLC-SCC); Breast Cancer, Breast Neoplasms; Endometrial Cancer, Endometrial Neoplasm; Ovarian Cancer, Ovarian Neoplasms
• Intervention / Treatment: Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells.

Detailed Description

The trial is an open-label, multi-center safety trial of GEN1047. The trial consists of two parts: a dose escalation part ("escalation" - phase 1) and an expansion part ("expansion" - phase 2a). The goal of the dose escalation part is to find out if GEN1047 is safe in participants with specific solid tumors and to find the best dose(s). In the expansion part of the trial up to two doses of GEN1047 will be tested.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet (Copenhagen University Hospital)
• France
  • Besançon, France, 25030
    • CHU de Besançon
  • Bordeaux, France
    • Institut Bergonie
  • Lyon, France, 69008
    • Centre Leon Berard
  • Montpellier, France, 34298
    • Institut du Cancer de Montpellier
  • Paris, France, 75248
    • Institut Curie
  • Paris, France
    • Hôpital Cochin
  • Poitiers, France
    • CHU Poitiers - Hôpital la Milétrie
  • Toulouse, France
    • Institut Claudius Regaud
  • Villejuif, France, 75005
    • Institut Gustave Roussy
• Italy
  • Milan, Italy, 435
    • IEO Istituto Europeo di Oncologia
  • Monza, Italy, 20900
    • Fondazione IRCCS San Gerardo dei Tintori
• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen
  • Nijmegen, Netherlands, 6525GA
    • Radboudumc
  • Rotterdam, Netherlands, 3015CE
    • Erasmus Medisch Centrum
• Poland
  • Poznan, Poland
    • Med-Polonia Sp. z o.o
• Spain
  • Barcelona, Spain
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Madrid, Spain
    • Next Oncology Madrid
  • Madrid, Spain, 28050
    • Centro Oncologico Clara Campal
  • Madrid, Spain, 2815
    • Hospital Universitary Fundacion Jimenez Diaz
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • University College London Hospital
  • London, United Kingdom, EC1A7BE
    • St Bartholomews Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Department of Medicine Hematology Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale University - Yale Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

Criteria - Escalation Part:

• Participant must have histologically or cytologically confirmed solid tumor(s) in any of the following selected indications for which there is no further available standard therapy likely to confer clinical benefit (or participant is not a candidate or has previously refused such earlier available therapy), and for whom, in the opinion of the investigator, experimental therapy with GEN1047 may be beneficial (breast cancer, endometrial cancer, ovarian cancer, NSCLC-SCC.
• Participants with ovarian cancer must have documented progressive disease (PD) on or after last prior treatment and within 60 days of screening.
• Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) on the day of signing informed consent.
• Must have either recurrence after, or progression on or lack of response to available relevant standard of care (SoC) anticancer therapies; or are deemed intolerant to or ineligible for, standard curative therapy in the recurrent setting.
• Must have at least 1 measurable lesion per RECIST v1.1. The measurable lesion(s) must be outside the field of radiation therapy (RT) if there was prior treatment with RT.
• Must have an Eastern Cooperative Oncology Group performance status (ECOGPS) score of 0 to 1 at Screening and on C1D1 pretreatment.
• Should provide a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

Criteria - Expansion Part Stage 1, 1b and Stage 2:

• Participants must have documented PD according to RECIST v1.1 on or after last prior treatment with latest scan performed a maximum of 28 days prior to the first dose.
• Participant must have advanced (unresectable) or metastatic, histologically confirmed diagnosis (breast cancer, endometrial cancer, ovarian cancer.
• Must be a female and at least 18 years of age (or the legal age of consent in the jurisdiction in which the trial is taking place) at the time of consent.
• Must have at least 1 measurable lesion per RECIST v1.1 as assessed by local investigator.
• Must have an ECOG- PS score of 0 to 1 at Screening and on Cycle 1 Day 1 (C1D1) pretreatment.
• Must submit a tumor tissue sample during the Screening period and prior to C1D1.
• Provide all tumor-assessing pre-trial CT scans since failure of last prior therapy.

Key Exclusion Criteria:

• Significant cardiovascular impairment within 6 months of the first dose of trial drug.
• Participant with new or progressive brain metastases or spinal cord compression.
• Participant has been exposed to any prior therapy with a compound targeting CD3 and/or B7H4 or cell based therapies.
• Current pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of non-infectious drug-, immune-, or radiation-related pneumonitis that required steroid.

Note: Other protocol defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GEN1047	Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells.; GEN1047 will be administered as an intravenous infusion. The dose-levels will be determined by the starting dose and the escalation steps taken in the trial.; Other Names: DuoBody®-CD3-H101GxB7H4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expansion: Objective Response Rate (ORR)	ORR is defined as percentage of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1.	Up to 5 years
Escalation: Number of Participants with Dose Limiting Toxicities (DLT)	DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), v5.0.	From the first Cycle (Cycle length=21 days) in each cohort
Escalation: Number of Participants with Treatment Emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is defined as an AE occurring or worsening between the first dose of study drug and 30 days after the last dose received.	From first dose date up to end of the safety follow up period, 30 days after last dose (approximately 4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Escalation and Expansion: Clearance		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Volume of Distribution (Vd)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Area Under the Concentration-time Curve from Time 0 to Time of Last Dose (AUClast)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Maximum (Peak) Plasma Concentration (Cmax)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Time to Reach Cmax (Tmax)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Elimination half-life (t 1/2)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Number of Participants with Anti-Drug Antibody (ADA)		Up to 5 years
Escalation: ORR	ORR is defined as percentage of participants with BOR of confirmed CR or confirmed PR based on RECIST v1.1.	Up to 5 years
Escalation and Expansion: Duration of Response (DOR)	DOR is defined as the time from the first documented response to the first documented progression or death due to any cause.	Up to 5 years
Escalation and Expansion: Time to response (TTR)	Time to response (TTR) is defined as the time from the date of Cycle 1 Day 1 (C1D1) to the first documented response of either confirmed CR or confirmed PR.	Up to 5 years
Expansion: Progression Free Survival (PFS)	PFS is defined as the time from the date of C1D1 to the date of the first documented progression or death due to any cause, whichever occurs earlier according to RECIST v1.1.	Up to 5 years
Expansion: Overall Survival (OS)	OS is defined as the time from date of C1D1 to date of death due to any cause.	Up to 5 years
Escalation and Expansion: AUC From Time Zero to Infinity (AUC0-inf)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Plasma Trough (Pre-dose) Concentrations (Ctrough)		Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
Escalation and Expansion: Disease control rate (DCR)	The disease control rate (DCR) is defined as the percentage of participants with BOR of confirmed CR, confirmed PR, or stable disease (SD) according to RECIST v1.1	Up to 5 years
Expansion: Number of Participants with TEAEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAE is defined as an AE occurring or worsening between the first dose of study drug and 30 days after the last dose received.	From first dose date up to end of the safety follow up period, 60 days after last dose (approximately 5 months)

Collaborators and Investigators

• Sponsor: Genmab
• Investigators: Study Director: Study Official, Genmab

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): March 25, 2026
• Study Completion (Actual): March 25, 2026

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Uterine Neoplasms; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Breast Neoplasms; Endometrial Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Antibodies; Antibodies, Bispecific
• Other Study ID Numbers: GCT1047-01; 2021-001790-23 (EudraCT Number); NL82658.056.23 (Registry Identifier: CCMO (The Netherlands)); 1007620 (Registry Identifier: Research Summaries Database (UK)); 2024-510722-10 (Other Identifier: EU Trial (CTIS) Number); RECF-004736 (Other Identifier: The French National Cancer Institute)

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