A study comparing talquetamab plus pomalidomide, talquetamab plus teclistamab, and elotuzumab, pomalidomide, and dexamethasone or pomalidomide, bortezomib, and dexamethasone in participants with relapsed or refractory myeloma who have received an Anti-CD38 antibody and lenalidomide

ISRCTN	ISRCTN74178658
DOI	https://doi.org/10.1186/ISRCTN74178658
ClinicalTrials.gov (NCT)	NCT06208150
Clinical Trials Information System (CTIS)	2022-502446-27
Integrated Research Application System (IRAS)	1008541
Protocol serial number	64407564MMY3009, CPMS 57469, IRAS 1008541
Sponsor	Janssen-Cilag International NV
Funder	Janssen Research and Development

Submission date: 12/10/2023
Registration date: 15/12/2023
Last edited: 03/03/2025

Recruitment status: No longer recruiting
Overall study status: Ongoing
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
Multiple myeloma is a blood cancer that affects certain types of white blood cells called plasma cells. Although treatments are available, multiple myeloma can come back after treatment or be resistant to standard treatment. Drugs that redirect T cells (a type of white blood cell) to attack cancer cells may be an effective means to destroy cancer cells leading to a long-term treatment response. Talquetamab (also known as JNJ-64407564 or Tal or Talvey) and teclistamab (JNJ-64007957 or Tec or Tecvayli) are modified antibodies* that bind to proteins on the surface of multiple myeloma cells and T cells, which activates T cells and kills tumor cells. *Antibody is a protein that helps protect the body against foreign matter, such as bacteria and viruses. In this study, researchers want to learn about the effectiveness of Tal-pomalidomide (Tal-P) or Tal-Tec compared to elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd). One way to see how well a new treatment works is to measure the time it takes for the disease to come back or get worse. Participants will have an equal chance of receiving either Tal-P or Tal-Tec in addition to EPd or PVd treatment chosen by the study doctor. This is an open-label study, which means that the participant, caregiver, and the study doctor will know about the study drug received.

Who can participate?
Patients aged 18 years old and over, diagnosed with multiple myeloma who have been previously treated with 1 to 4 lines of treatments in the past, to which they either did not respond or after which their multiple myeloma has come back.

What does the study involve?
The study will be conducted in 3 phases:
1. Screening Phase: Participants will be screened and enrolled into the study.
2. Treatment Phase: Participants will be randomly divided into 3 groups:
Arm A: Participants will receive Tal-P
Arm B: Participants will receive Tal-Tec
Arm C: Participants will receive either EPd or PVd as per the investigator's choice
3. Follow-up: Participants will be monitored for their health for up to 8 weeks after the last dose of study treatment.

Participants will undergo a safety assessment which includes adverse events, laboratory test results, physical examination findings, assessment of the Eastern Cooperative Oncology Group (ECOG) performance status grade, pharmacokinetics (body does to a drug), and immunogenicity (ability of a foreign substance to enter a person's body and cause an immune response), and biomarkers (an objective measure that captures what is happening in a cell or an organism) will be assessed at specified time points. The overall duration of study is approximately 6 years 5 months.

What are the possible benefits and risks of participating?
There is no established benefit to participants of this study. Based on scientific theory and clinical data, taking talquetamab and teclistamab may improve relapsed or refractory multiple myeloma. However, this cannot be guaranteed because talquetamab and teclistamab are still under investigation as a treatment and it is not known whether talquetamab and teclistamab will work. If participants are put in the comparator group, they will not receive talquetamab and teclistamab.
Participants may experience some benefit from participation in the study that is not due to receiving study drug, but due to regular visits and assessments monitoring overall health. Participation may help other people with relapsed or refractory myeloma in the future. Participants may have side effects from the drugs or procedures used in this study that may be mild to severe and even life-threatening, and they can vary from person to person. The most common, known risks are getting symptoms such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, skin and nail changes, weight loss, systemic administration-related reaction, cytopenias, infections, injection-site reaction, immune-related adverse events, neurological side effects such as
co-ordination, balance and speech disorders and hypogammaglobulinemia after getting the study drug or not. There are other, less frequent risks. The participant information sheet and informed consent form, which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining the known risks of participating in the study.
Not all possible side effects and risks related to talquetamab and teclistamab are known at this moment. During the study, the sponsor may learn new information about talquetamab and teclistamab. The study doctor will tell participants as soon as possible about any new information that might make them change their minds about being in the study, such as new risks.
To minimise the risk associated with taking part in the study, participants are frequently reviewed for any side effects and other medical events. Participants are educated to report any such events to the study doctor who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a specialist drug safety team. There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study-related costs (e.g., travel/parking costs).

Where is the study run from?
Janssen-Cilag International NV (Netherlands)

When is the study starting and how long is it expected to run for?
October 2023 to June 2027

Who is funding the study?
Janssen-Cilag International NV (Netherlands)

Who is the main contact?
JanssenUKRegistryQueries@its.jnj.com

Contact information

Dr Janssen UK registry
Scientific

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

Phone	None provided
Email	JanssenUKRegistryQueries@its.jnj.com

Dr Dean Smith
Principal investigator

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Dr Medical Information and Product Information Enquiry
Scientific

Janssen Research and Development
50-100 Holmers Farm Way
High Wycombe, Buckinghamshire
HP12 4DP
United Kingdom

Phone	+44 (0)800 731 8450
Email	medinfo@its.jnj.com

Study information

Primary study design	Interventional
Study design	Randomized controlled open-label parallel-group study
Secondary study design	Randomised controlled trial
Scientific title	A phase III randomized study comparing talquetamab in combination with pomalidomide (Tal-P), talquetamab in combination with teclistamab (Tal-Tec), and investigator’s choice of either elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd) in participants with relapsed or refractory myeloma who have received 1 to 4 prior lines of therapy including an Anti-CD38 antibody and lenalidomide
Study acronym	MonumenTAL-6
Study objectives	The purpose of this study is to compare the effectiveness of either talquetamab plus pomalidomide (Tal-P) or talquetamab plus teclistamab (Tal-Tec) with elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd).
Ethics approval(s)	Approved 07/12/2023, East Midlands - Derby Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; None available; derby.rec@hra.nhs.uk), ref: 23/EM/0251
Health condition(s) or problem(s) studied	Relapsed or refractory myeloma
Intervention	Arm A: Talquetamab + Pomalidomide (Tal-P) Participants will receive talquetamab as subcutaneous (SC) injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Arm B: Talquetamab + Teclistamab (Tal-Tec)- Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)- Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidomide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Talquetamab, teclistamab, pomalidomide, dexamethasone, bortezomib, elotuzumab
Primary outcome measure(s)	Progression-free survival defined as the duration from the date of randomization to either progressive disease or death, whichever comes first, measured up to 7 years and 2 months.
Key secondary outcome measure(s)	1. Overall response is defined as the percentage of participants with the best overall response of partial response (PR) or better according to international myeloma working group (IMWG) response criteria, measured up to 7 years 2 months. 2. Complete Response (CR) or better is defined as the percentage of participants with the best overall response of CR or better according to IMWG response criteria, measured up to 7 years 2 months. 3. Very Good Partial Response or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria, measured up to 7 years 2 months. 4. Minimal Residual Disease-negative CR is defined as the percentage of participants who achieve both CR or better and MRD negativity at a threshold of 10^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy (SST), measured up to 7 years 2 months. 5. Overall Survival (OS) is defined as the time from randomization to the date of participant's death, measured up to 7 years 2 months. 6. Progression Free Survival on Next-line Therapy (PFS2) is defined as time from randomization to progression on the next line of therapy or death, whichever comes first, measured up to 7 years 2 months. 7. Time To Next Treatment (TTNT) is defined as the time from randomization to the start of SST, measured up to 7 years 2 months. 8. Serum concentrations Talquetamab and teclistamab will be reported, measured up to 7 years 2 months. 9. Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab and Teclistamab will be reported, measured up to 7 years 2 months. 10. Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm- Q). Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale. This will be measured up to 7 years 2 months. 11. Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30. Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. This will be measured up to 7 years 2 months. 12. Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L). Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). This will be measured up to 7 years 2 months. 13. Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Patient Global Impression –Severity (PGI- S). Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from “none” to “very severe.” This will be measured up to 7 years 2 months. 14. Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey. Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes. developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey. This will be measured up to 7 years 2 months. 15. Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by MySIm-Q. Change from baseline in symptoms, functioning, and HRQoL as assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale. This will be measured up to 7 years 2 months. 16. Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ- C30. Change from baseline in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems. This will be measured up to 7 years 2 months. 17. Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EQ-5D-5L. Change from baseline in symptoms, functioning, and HRQoL as assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). This will be measured up to 7 years 2 months. 18. Change from Baseline in Symptoms, Functioning, and Health- related Quality of Life (HRQoL) as Assessed by PGI-S. Change from baseline in symptoms, functioning, and HRQoL as assessed by PGI-S will be reported. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from “none” to “very severe." This will be measured up to 7 years 2 months. 19. Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey. Change from baseline in symptoms, functioning, and HRQoL as assessed by epstein taste survey will be reported. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes. developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey. This will be measured up to 7 years 2 months. 20. Percentage of Participants With Meaningful Improvement in HRQoL as Assessed by EORTC-QLQ- C30. Percentage of participants with meaningful improvement in HRQol as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems. This will be measured up to 7 years 2 months.
Completion date	14/06/2027

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	18 Years
Sex	All
Target sample size at registration	795
Key inclusion criteria	1. Documented multiple myeloma as defined by the criteria below: 1.1. Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria 1.2. Measurable disease at screening as assessed by the central laboratory, defined by any of the following: 1.2.1. Serum M-protein level greater than or equal to (>=) 0.5 gram per deciliter (g/dL); or 1.2.2. Urine M-protein level >= 200 milligrams (mg) per 24 hours; or 1.2.3. Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio 2. Relapsed or refractory disease as defined below: 2.1. Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment 2.2. Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment 3. Documented evidence of PD or failure to achieve a minimal response to the last line of therapy based on the investigator’s determination of response by IMWG criteria on or after their last regimen 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment 5. A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6months after the last dose of study treatment
Key exclusion criteria	1. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients 2. Stroke, transient ischemic attack, or seizure within 6 months prior to signing the informed consent form (ICF) 3. Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment 4. A maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within the 14-day period before the first dose of the study drug Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole-brain magnetic resonance imaging (MRI) and lumbar cytology are required.
Date of first enrolment	29/01/2024
Date of final enrolment	29/09/2025

Locations

Countries of recruitment

United Kingdom
England
Scotland
Wales
Argentina
Australia
Austria
Belgium
Brazil
Canada
China
Czech Republic
Denmark
France
Germany
Greece
Hungary
India
Israel
Italy
Japan
Korea, South
Netherlands
Poland
Saudi Arabia
Spain
Sweden
Türkiye
United States of America

Study participating centres

Nottingham City Hospital

Hucknall Road
Nottingham
NG5 1PB
United Kingdom

University of Wales

Heath Park
Cardiff
CF14 4XW
United Kingdom

Kings College Hospital

Denmark Hill
London
SE5 9RS
United Kingdom

Ninewells Hospital

Ninewells Avenue
Dundee
DD1 9SY
United Kingdom

Leeds Teaching Hospitals NHS Trust

St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Derriford Hospital

Derriford Road
Crownhill
Plymouth
PL6 8DH
United Kingdom

Queen Alexandra Hospital

Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom

Sarah Cannon Research Institute UK

93 Harley Street
London
W1G 6AD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Study results will be available via publication in scientific journals, the EudraCT database & presentation at scientific meetings. Results will be made available to participants via a Plain Language Summary a year after the end of the study. The summary will describe the results regardless of study outcome in language that is understandable to the general public. It will not contain individual participant results or their personal information. A copy of the Summary will be provided to the REC. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at 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.

Editorial Notes

03/03/2025: The plain English summary was updated.
08/04/2024: ClinicalTrials.gov number added.
14/03/2024: Internal review.
09/01/2024: Internal review.
12/10/2023: Trial's existence confirmed by Health Research Authority (HRA) (UK).