A study of JNJ-80038114 in participants with advanced stage prostate cancer

ISRCTN	ISRCTN16457874
DOI	https://doi.org/10.1186/ISRCTN16457874
ClinicalTrials.gov (NCT)	NCT05441501
Clinical Trials Information System (CTIS)	2022-001263-27
Integrated Research Application System (IRAS)	1005794
Protocol serial number	80038114PCR1001, IRAS 1005794, CPMS 53090
Sponsor	Janssen-Cilag International NV
Funder	Janssen-Cilag International NV

Submission date: 04/01/2023
Registration date: 13/01/2023
Last edited: 24/04/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
The purpose of this study is to see if a new study drug can be used in future studies for the treatment of prostate cancer. During the study, side effects caused by the study drug will be followed closely, as well as how long the study drug stays in the body and how the body responds to it.
This is the first time that the study drug is being tested in humans. It is not approved for use by humans in any country.
Therefore, Part 1 of the study will start with the administration of a low dose of the study drug. After reviewing the results obtained at each dose level, it will be decided whether or how much to increase the dose for subsequent participants.

Who can participate?
This study will include participants aged 18 years and over with metastatic castration-resistant prostate cancer.

What does the study involve?
This study consists of a screening phase, a treatment phase and an end-of-treatment visit. All participants will receive the study drug via subcutaneous (below the skin) injections. The dose and frequency of the injections will depend on when a participant enters the study.
The duration of participation is determined by the duration of the study drug administration.
Administration of the study drug will last as long as a participant benefits and does not have unmanageable side effects. In addition, participants and physicians can decide to stop the study drug at any time.
At study visits, a participant will have procedures such as blood and urine tests, ECG, physical exam, CT / MRI or bone scan. An additional fresh tumour biopsy may be collected during Part 2 of the study. Hospitalisation will also be required to monitor for any side effects during the first one or more doses of the study drug in Part 1.

What are the possible benefits and risks of participating?
This is the first study of this study drug in humans. It is possible that taking part in this study could improve a participant’s condition, but this is not guaranteed to happen.
During the study, a participant’s condition may stay the same or get worse.
Based on clinical trials of other active substances that target prostate‐specific membrane antigen (also referred to as PSMA, a common protein in patients with prostate cancer) and the immune system, potential side effects have been outlined in the participant information sheet. This sheet will be signed by every participant agreeing to participate in the study and includes a section describing these potential side effects.
This is the first time the study drug will be given to humans, so we do not yet know if these potential side effects will occur or how frequently they may occur. Different side effects may occur. There may be risks to using the study drug that we don’t know yet.
Tests and procedures will be done during the study to monitor side effects. Participants will also be educated to report any symptoms they experience during the study to their study doctor, even if they do not think the side effects are related to the study drug or procedures.

Where is the study run from?
Janssen Research & Development, LLC (Belgium) is the Sponsor of this study.
Participating centers (Hospitals) are located in the UK, US, France and Germany.

When is the study starting and how long is it expected to run for?
January 2022 to September 2024

Who is funding the study?
Janssen Research & Development, LLC (Belgium)

Who is the main contact?
Larissa Bates, janssenukregistryqueries@its.jnj.com

Contact information

Dr Medical Information & Product Information Enquiry
Scientific

50-100 Holmers Farm Way
High Wycombe
HP12 4EG
United Kingdom

Phone	+44 8007318450 / +44 1494567444
Email	medinfo@its.jnj.com

Mrs Larissa Bates
Public

50-100 Holmers Farm Way
High Wycombe
HP12 4EG
United Kingdom

Phone	+44 1494567444
Email	janssenukregistryqueries@its.jnj.com

Dr Andrew Hudson
Principal investigator

The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Study information

Primary study design	Interventional
Study design	Interventional non-randomized open-label multicenter study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	A phase 1 study of JNJ-80038114, a T-Cell redirecting agent targeting prostate specific membrane antigen (PSMA), for advanced stage prostate cancer
Study objectives	The main goals of this study are: 1. To determine the appropriate doses of the study drug and, 2. To evaluate any side effects. The secondary goals of this study are: 1. To evaluate the cancer cells’ response to the study drug and, 2. To provide an understanding of how the body reacts to the study drug and how long the study drug remains in the body.
Ethics approval(s)	Approved 03/10/2022, West London and GTAC Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 207 1048 007; westlondon.rec@hra.nhs.uk), ref: 22/LO/0556
Health condition(s) or problem(s) studied	Prostate cancer
Intervention	The study is split into two parts: Part 1, dose-escalation: Participants will receive JNJ-80038114. The dose levels will be escalated based on the dose-limiting toxicities (DLTs) observed and then reviewed by the study evaluation team (SET). Part 2, dose expansion: Participants will receive JNJ-80038114 at the recommended Phase 2 dose (RP2D) determined in Part 1. Duration of participation is determined by the duration of study drug administration: administration of the study drug will last as long as a participant is receiving benefit and does not have unmanageable side effects. In addition, participant and physician can decide to stop the study drug at any time. There will be just one FU visit at 30-days post treatment.
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	JNJ-80038114
Primary outcome measure(s)	The timeframe for monitoring/measuring each of these is up to 2 years and 6 months: Parts 1 and 2: 1. Number of Participants With Adverse Events (AEs). An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. 2. Number of Participants With AEs by Severity. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Part 1 only: 3. Number of Participants With Dose-Limiting Toxicity (DLT) . Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Key secondary outcome measure(s)	The timeframe for monitoring/measuring each of these is up to 2 years and 6 months: 1. Serum Concentration of JNJ-80038114 - Serum concentration of JNJ-80038114 will be determined. 2. Systemic Cytokine Concentrations - Cytokine concentrations will be determined for biomarker assessment. 3. Serum Prostate Specific Antigen (PSA) Concentration - Serum PSA concentration will be determined. 4. Number of Participants With Antibodies to JNJ-80038114 - Serum samples will be analysed for the detection of antibodies to JNJ-80038114 using a validated assay method. 5. Objective Response Rate (ORR) - ORR is defined as the percentage of participants who have a partial response (PR) or better according to Prostate Cancer Working Group 3 (PCWG3) response criteria. 6. PSA Response Rate - PSA response rate is defined as the percentage of participants with a confirmed decline in PSA of 50 percent (%) or more from baseline. 7. Duration of Response (DOR) - DOR is defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the PCWG3 response criteria, or death due to any cause, whichever occurs first.
Completion date	29/09/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Male
Target sample size at registration	90
Total final enrolment	49
Key inclusion criteria	1. 18 years and older 2. Metastatic castration-resistant prostate cancer (mCRPC) with confirmed adenocarcinoma of the prostate as defined by Prostate Cancer Working Group 3 (PCWG3) 3. Measurable or evaluable disease 4. At least 1 prior treatment for mCRPC 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Adequate organ functions as defined by certain laboratory values 7. Must sign an informed consent form (ICF) 8. Participants must agree to use a highly effective form of birth control as guided by the study doctor
Key exclusion criteria	1. Concurrent anticancer therapy 2. Severe or long-lasting side effects related to prior anticancer therapy 3. Known allergies to JNJ-80038114 or its excipients 4. Brain metastasis or known seizure history 5. Significant infections or lung, heart or other medical conditions
Date of first enrolment	14/12/2022
Date of final enrolment	19/01/2024

Locations

Countries of recruitment

United Kingdom
England
France
Germany
United States of America

Study participating centres

The Christie NHS Foundation Trust - Christie Hospital

Manchester
M20 4BX
United Kingdom

The Royal Marsden Hospital

Sutton
SM2 5PT
United Kingdom

University College London Hospital (ULCH)

London
NW1 2PG
United Kingdom

Sarah Cannon Research Institute

Nashville
37203
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated and analysed during the current study will be available upon request. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at https://www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at yoda.yale.edu.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

24/04/2024: The following changes were made to the study record:
1. Total final enrolment added.
2. The recruitment end date was changed from 30/10/2024 to 19/01/2024.
3. The overall study end date was changed from 31/03/2025 to 29/09/2024.
4. The intention to publish date was changed from 30/03/2026 to 29/09/2025.
5. Universitätsklinikum Düsseldorf and Gustave Roussy were removed from the study participating centres.
01/02/2023: Internal review.
13/01/2023: Trial's existence confirmed by West London and GTAC Research Ethics Committee.