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

NCT05180474 | Terminated Phase 1 FDA Drug

• 6 other identifiers: GCT1047-01NL82658.056.2310076202021-001790-232024-510722-10RECF-004736
• Study Type: interventional
• Target: 179
• Locations: 9 countries
• Sites: 36

Brief Summary

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.

Conditions

Endometrial Cancer, Endometrial Neoplasm; Ovarian Cancer, Ovarian Neoplasms; Squamous Non Small Cell Lung Cancer (NSCLC-SCC); Breast Cancer, Breast Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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)

• 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

Secondary Outcomes (16)

• 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: AUC From Time Zero to Infinity (AUC0-inf)

  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)

Study Arms (1)

GEN1047

EXPERIMENTAL

Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells.

Interventions

GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells. BIOLOGICAL

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.

Also known as: DuoBody®-CD3-H101GxB7H4

GEN1047

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genmab: lead

Study Sites (36)

UCLA Department of Medicine Hematology Oncology

Los Angeles, California, 90024, United States

Location

Yale University - Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Rigshospitalet (Copenhagen University Hospital)

Copenhagen, 2100, Denmark

Location

CHU de Besancon

Besançon, 25030, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut Curie

Paris, 75248, France

Location

Hôpital Cochin

Paris, France

Location

CHU Poitiers - Hôpital la Milétrie

Poitiers, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, 75005, France

Location

IEO Istituto Europeo di Oncologia

Milan, 435, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

Location

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

Radboudumc

Nijmegen, 6525GA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015CE, Netherlands

Location

Med-Polonia Sp. z o.o

Poznan, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Centro Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitary Fundacion Jimenez Diaz

Madrid, 2815, Spain

Location

NEXT Oncology Madrid

Madrid, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

St Bartholomews Hospital

London, EC1A7BE, United Kingdom

Location

University College London Hospital

London, NW1 2BU, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Study Official

  Genmab

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: January 6, 2022
• Study Start: December 13, 2021
• Primary Completion: March 25, 2026
• Study Completion: March 25, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9); BE (2); NL (3); DK (1); PL (1); GB (3); US (6); ES (9); IT (2)