A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)
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| ClinicalTrials.gov Identifier: NCT04634552 |
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Recruitment Status :
Recruiting
First Posted : November 18, 2020
Last Update Posted : April 24, 2024
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Sponsor:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hematological Malignancies | Drug: Talquetamab | Phase 2 |
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Talquetamab is a humanized immunoglobulin G4 proline, alanine, alanine (IgG4PAA) bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). This study consists of 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT (30 days (+ 7 days)] visit); and a post-treatment follow-up phase (until the end of study unless the participant has died, is lost to follow up or has withdrawn consent). Total duration of study is up to 2 years (after the last participant receives their first dose). Safety, pharmacokinetics (PK), laboratory tests, and questionnaire will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study. The corresponding study (NCT03399799) is the Phase 1 part of the study and TALMMY1001- Part 3 is the Phase 2 part of the study.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 450 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma |
| Actual Study Start Date : | February 1, 2021 |
| Estimated Primary Completion Date : | March 31, 2026 |
| Estimated Study Completion Date : | December 31, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part 3: Cohort A (Talquetamab)
Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.
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Drug: Talquetamab
Talquetamab will be administered SC until disease progression.
Other Name: JNJ-64407564 |
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Experimental: Part 3: Cohort B (Talquetamab)
Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.
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Drug: Talquetamab
Talquetamab will be administered SC until disease progression.
Other Name: JNJ-64407564 |
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Experimental: Part 3: Cohort C (Talquetamab)
Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.
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Drug: Talquetamab
Talquetamab will be administered SC until disease progression.
Other Name: JNJ-64407564 |
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Experimental: Part 3: Cohort D (Talquetamab)
Cohort D will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.
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Drug: Talquetamab
Talquetamab will be administered SC until disease progression.
Other Name: JNJ-64407564 |
Primary Outcome Measures :
- Overall Response Rate (ORR) [ Time Frame: Up to 2 years and 10 months ]ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.
Secondary Outcome Measures :
- Duration of Response (DOR) [ Time Frame: Up to 2 years and 10 months ]DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria, or death due to PD, whichever occurs first.
- Very Good Partial Response (VGPR) or Better Rate [ Time Frame: Up to 2 years and 10 months ]VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.
- Complete Response (CR) or Better Rate [ Time Frame: Up to 2 years and 10 months ]CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.
- Stringent Complete Response (sCR) Rate [ Time Frame: Up to 2 years and 10 months ]sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.
- Time to Response (TTR) [ Time Frame: Up to 2 years and 10 months ]TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.
- Progression-Free Survival (PFS) [ Time Frame: Up to 2 years and 10 months ]PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Up to 2 years and 10 months ]OS is defined as the time from the date of first dose of study drug to the date of the participant's death.
- Minimal Residual Disease (MRD) Negative Rate [ Time Frame: Up to 2 years and 10 months ]MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years and 10 months ]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.
- Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years and 10 months ]An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
- Number of Participants with AEs by Severity [ Time Frame: Up to 2 years and 10 months ]Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). 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.
- Number of Participants with Abnormalities in Clinical Laboratory Values [ Time Frame: Up to 2 years and 10 months ]Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.
- Serum Concentration of Talquetamab [ Time Frame: Up to 2 years and 10 months ]Serum samples will be analyzed to determine concentrations of talquetamab.
- Number of Participants with Talquetamab Antibodies [ Time Frame: Up to 2 years and 10 months ]Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.
- Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) [ Time Frame: Baseline up to 2 years and 10 months ]The EORTC- QLQ-Core-30 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/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("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 higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
- Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) [ Time Frame: Baseline up to 2 years and 10 months ]The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.
- Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) [ Time Frame: Baseline up to 2 years and 10 months ]The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).
- Overall Response Rate (ORR) in Participants with High-risk Molecular Features [ Time Frame: Up to 2 years and 10 months ]ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
- Part 3: Measurable disease cohort A, cohort B, cohort C, and cohort D: multiple myeloma must be measurable by central laboratory assessment
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
- Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine
- Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion Criteria:
- Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B and Cohort D: T cell redirection therapy within 3 months
- Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
- Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
- Stroke or seizure within 6 months prior to signing the informed consent form (ICF)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04634552
Contacts
| Contact: Study Contact | 844-434-4210 | Participate-In-This-Study@its.jnj.com |
Locations
Show 77 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
| Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Additional Information:
| Responsible Party: | Janssen Research & Development, LLC |
| ClinicalTrials.gov Identifier: | NCT04634552 |
| Other Study ID Numbers: |
CR108920 2017-002400-26 ( EudraCT Number ) TALMMY1001-PT3 ( Other Identifier: Janssen Research & Development, LLC ) 2023-504581-29-00 ( Registry Identifier: EUCT number ) |
| First Posted: | November 18, 2020 Key Record Dates |
| Last Update Posted: | April 24, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu |
| URL: | https://www.janssen.com/clinical-trials/transparency |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Janssen Research & Development, LLC:
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Multiple Myeloma |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Hematologic Neoplasms Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Neoplasms by Site |