GEN1047 for Solid Tumors - First in Human (FIH) Trial
- Conditions
- Ovarian Cancer, Ovarian NeoplasmsEndometrial Cancer, Endometrial NeoplasmSquamous Non Small Cell Lung Cancer (NSCLC-SCC)Breast Cancer, Breast Neoplasms
- Interventions
- Biological: GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells.
- Registration Number
- NCT05180474
- Lead Sponsor
- Genmab
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 179
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GEN1047 GEN1047 is a bispecific antibody that induces T-cell mediated cytotoxicity of B7H4-positive tumor cells. -
- Primary Outcome Measures
Name Time Method Expansion: Objective Response Rate (ORR) Up to 5 years 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.
Escalation: Number of Participants with Treatment Emergent Adverse Events (TEAEs) From first dose date up to end of the safety follow up period, 30 days after last dose (approximately 4 months) 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.
Escalation: Number of Participants with Dose Limiting Toxicities (DLT) From the first Cycle (Cycle length=21 days) in each cohort DLTs will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), v5.0.
- Secondary Outcome Measures
Name Time Method Escalation and Expansion: Volume of Distribution (Vd) 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: Clearance Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days) Escalation and Expansion: Time to response (TTR) Up to 5 years 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.
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: Elimination half-life (t 1/2) 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: ORR Up to 5 years ORR is defined as percentage of participants with BOR of confirmed CR or confirmed PR based on RECIST v1.1.
Escalation and Expansion: Duration of Response (DOR) Up to 5 years DOR is defined as the time from the first documented response to the first documented progression or death due to any cause.
Escalation and Expansion: Time to Reach Cmax (Tmax) 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 and Expansion: Disease control rate (DCR) Up to 5 years 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
Expansion: Progression Free Survival (PFS) Up to 5 years 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.
Expansion: Overall Survival (OS) Up to 5 years OS is defined as the time from date of C1D1 to date of death due to any cause.
Expansion: Number of Participants with TEAEs From first dose date up to end of the safety follow up period, 60 days after last dose (approximately 5 months) 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.
Trial Locations
- Locations (36)
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
UCLA Department of Medicine Hematology Oncology
🇺🇸Los Angeles, California, United States
Yale University - Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Antwerp University Hospital
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Rigshospitalet (Copenhagen University Hospital)
🇩🇰Copenhagen, Denmark
CHU de Besancon
🇫🇷Besançon, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut du Cancer de Montpellier
🇫🇷Montpellier, France
Institut Curie
🇫🇷Paris, France
Hôpital Cochin
🇫🇷Paris, France
CHU Poitiers - Hôpital la Milétrie
🇫🇷Poitiers, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France
IEO Istituto Europeo di Oncologia
🇮🇹Milan, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Italy
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Radboudumc
🇳🇱Nijmegen, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Med-Polonia Sp. z o.o
🇵🇱Poznań, Poland
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Centro Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitary Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
NEXT Oncology Madrid
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
St Bartholomews Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom