Clinical trial NCT05180474: GEN1047 for Solid Tumors - First in Human (FIH) Trial
Official title: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1047 in Subjects With Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Breast Cancer, Breast Neoplasms
Endometrial Cancer, Endometrial Neoplasm
Ovarian Cancer, Ovarian Neoplasms
Squamous Non Small Cell Lung Cancer (NSCLC-SCC)
Lead sponsor: Genmab
Sponsor class: INDUSTRY
First posted: 2022-01-06
Enrollment: 179
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Escalation: Number of Participants with Dose Limiting Toxicities (DLT)
timeFrame: From the first Cycle (Cycle length=21 days) in each cohort
measure: Escalation: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose date up to end of the safety follow up period, 30 days after last dose (approximately 4 months)
measure: Expansion: Objective Response Rate (ORR)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Escalation and Expansion: Clearance
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Volume of Distribution (Vd)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Area Under the Concentration-time Curve from Time 0 to Time of Last Dose (AUClast)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: AUC From Time Zero to Infinity (AUC0-inf)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Maximum (Peak) Plasma Concentration (Cmax)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Time to Reach Cmax (Tmax)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Plasma Trough (Pre-dose) Concentrations (Ctrough)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Elimination half-life (t 1/2)
timeFrame: Predose and postdose at multiple timepoints of each Cycle (Cycle length=21 days)
measure: Escalation and Expansion: Number of Participants with Anti-Drug Antibody (ADA)
timeFrame: Up to 5 years
measure: Escalation: ORR
timeFrame: Up to 5 years
measure: Escalation and Expansion: Duration of Response (DOR)
timeFrame: Up to 5 years
measure: Escalation and Expansion: Time to response (TTR)
timeFrame: Up to 5 years
measure: Escalation and Expansion: Disease control rate (DCR)
timeFrame: Up to 5 years
measure: Expansion: Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Expansion: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Expansion: Number of Participants with TEAEs
timeFrame: From first dose date up to end of the safety follow up period, 60 days after last dose (approximately 5 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Department of Medicine Hematology Oncology
state: California
city: New Haven
country: United States
facility: Yale University - Yale Cancer Center
state: Connecticut
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Copenhagen
country: Denmark
facility: Rigshospitalet (Copenhagen University Hospital)
city: Besançon
country: France
facility: CHU de Besancon
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital Cochin
city: Poitiers
country: France
facility: CHU Poitiers - Hôpital la Milétrie
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Milan
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o.o
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Madrid
country: Spain
facility: Centro Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitary Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: NEXT Oncology Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: St Bartholomews Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital
Study officials:
affiliation: Genmab
name: Study Official
role: STUDY_DIRECTOR
References: