Back to resultsA Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma (TRIMM-3)
Primary Purpose
Relapsed/ Refractory Multiple Myeloma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Talquetamab
Teclistamab
PD-1 Inhibitor
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/ Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Have documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
- Participants with relapsed or refractory disease that are not a candidate for available therapy with established clinical benefit
- Have measurable disease at screening as defined by at least 1 of the following: a) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL); b) Urine M-protein level >= 200 milligrams (mg) per 24 hours; c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams/deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
- Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Exclusion Criteria:
- Prior antitumor therapy within 21 days prior to the first dose of study treatment (proteasome inhibitor [PI] therapy or radiotherapy within 14 days, immunomodulatory drug (IMiD) agent therapy within 7 days, gene -modified adoptive cell therapy or autologous stem cell transplant within 3 months)
- Prior therapy with PD-1 inhibitors, allogeneic stem cell transplant or solid organ transplant
- Active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis
- Active Central Nervous System (CNS) involvement or exhibition of clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required
- Live, attenuated vaccine within 4 weeks before the first dose of study treatment
- Non-hematologic toxicity from prior anticancer therapy that has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia [any grade] or peripheral neuropathy to Grade <= 2)
- Received a cumulative dose of corticosteroids equivalent to >= 140 milligrams (mg) of prednisone within the 14-day period before the start of study treatment administration
Sites / Locations
- Colorado Blood Cancer InstituteRecruiting
- Icahn School of Medicine at Mount SinaiRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Wake Forest Baptist Medical CenterRecruiting
- Sarah Cannon Research InstituteRecruiting
- Vanderbilt - Ingram Cancer CenterRecruiting
- CHU de Montpellier, Hopital Saint-EloiRecruiting
- CHU de Nantes hôtel-DieuRecruiting
- CHU Poitiers - Hôpital la MilétrieRecruiting
- Institut Universitaire du Cancer Toulouse OncopoleRecruiting
- Universitätsklinikum Carl Gustav Carus DresdenRecruiting
- Universitaetsklinikum Hamburg EppendorfRecruiting
- Universitaetsklinikum HeidelbergRecruiting
- Universitätsklinikum WürzburgRecruiting
- Hosp. Univ. Germans Trias I PujolRecruiting
- Hosp. Univ. Fund. Jimenez DiazRecruiting
- Clinica Univ. de NavarraRecruiting
- Hosp. Clinico Univ. de SalamancaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1: Dose Escalation
Part 2: Dose Expansion
Arm Description
Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly.
Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1.
Outcomes
Primary Outcome Measures
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.
Number of Participants with Adverse Events (AEs) by Severity
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. 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.
Number of Participants with Abnormalities in Clinical Laboratory Assessments
Number of participants with abnormalities in clinical laboratory assessments (serum chemistry and hematology) will be reported.
Number of Participants with Dose-Limiting Toxicity (DLTs)
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Secondary Outcome Measures
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve partial response (PR) or better according to the International Myeloma Working Group (IMWG) 2016 criteria.
Very Good Partial Response (VGPR) or Better Response Rate
VGPR or better response rate is defined as the percentage of participants who achieve a VGPR or better response (stringent complete response [sCR]+ complete response [CR]+VGPR) according to the IMWG 2016 criteria.
Complete Response (CR) or Better Response Rate
CR or better response rate is defined as the percentage of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.
Stringent Complete Response (sCR) Rate
sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria.
Duration of Response
Duration of response 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 2016 criteria or death due to any cause, whichever occurs first.
Time to Response
Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better.
Serum Concentrations of Talquetamab
Serum samples will be analyzed to determine concentrations of Talquetamab using validated, specific, and sensitive immunoassay methods.
Serum Concentrations of Teclistamab
Serum samples will be analyzed to determine concentrations of Teclistamab using validated, specific, and sensitive immunoassay methods.
Serum Concentrations of PD-1 Inhibitor
Serum samples will be analyzed to determine concentrations of PD-1 inhibitor using validated, specific, and sensitive immunoassay methods.
Number of Participants with Anti-Talquetamab Antibodies
Number of participants with anti-talquetamab antibodies will be reported.
Number of Participants with Anti-Teclistamab Antibodies
Number of participants with anti-teclistamab antibodies will be reported.
Number of Participants with Anti-PD-1 Inhibitor Antibodies
Number of participants with anti-PD-1 inhibitor antibodies will be reported.
Full Information
NCT ID
NCT05338775
First Posted
March 31, 2022
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05338775
Brief Title
A Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
Acronym
TRIMM-3
Official Title
A Phase 1b Study of Bispecific T Cell Redirection Antibodies in Combination With Checkpoint Inhibition for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2022 (Actual)
Primary Completion Date
September 21, 2024 (Anticipated)
Study Completion Date
October 15, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to identify the safe dose(s) of a PD-1 inhibitor in combination with talquetamab or teclistamab, and to characterize the safety and tolerability of talquetamab or teclistamab when administered in combination with a PD-1 inhibitor.
Detailed Description
Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10 percent (%) of all hematologic cancers, making it the second most common hematologic malignancy. The overall rationale of this study is that talquetamab or teclistamab in combination with a PD-1 inhibitor may lead to enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through multiple mechanisms of action. The study will evaluate the clinical hypothesis that talquetamab or teclistamab can be safely administered at the selected dose when combined with a PD-1 inhibitor. The study will consist of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion) and a post treatment follow-up. End of study is defined as last study assessment for last participant in study. Total duration of study is up to 2 years 5 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/ Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
152 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly.
Arm Title
Part 2: Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1.
Intervention Type
Drug
Intervention Name(s)
Talquetamab
Intervention Description
Talquetamab will be administered as a subcutaneous (SC) injection.
Intervention Type
Drug
Intervention Name(s)
Teclistamab
Intervention Description
Teclistamab will be administered as a SC injection.
Intervention Type
Drug
Intervention Name(s)
PD-1 Inhibitor
Intervention Description
The PD-1 inhibitor will be administered as an intravenous injection.
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Adverse Events (AEs) by Severity
Description
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. 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.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Abnormalities in Clinical Laboratory Assessments
Description
Number of participants with abnormalities in clinical laboratory assessments (serum chemistry and hematology) will be reported.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Dose-Limiting Toxicity (DLTs)
Description
The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Time Frame
Up to 2 years 5 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants who achieve partial response (PR) or better according to the International Myeloma Working Group (IMWG) 2016 criteria.
Time Frame
Up to 2 years 5 months
Title
Very Good Partial Response (VGPR) or Better Response Rate
Description
VGPR or better response rate is defined as the percentage of participants who achieve a VGPR or better response (stringent complete response [sCR]+ complete response [CR]+VGPR) according to the IMWG 2016 criteria.
Time Frame
Up to 2 years 5 months
Title
Complete Response (CR) or Better Response Rate
Description
CR or better response rate is defined as the percentage of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.
Time Frame
Up to 2 years 5 months
Title
Stringent Complete Response (sCR) Rate
Description
sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria.
Time Frame
Up to 2 years 5 months
Title
Duration of Response
Description
Duration of response 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 2016 criteria or death due to any cause, whichever occurs first.
Time Frame
Up to 2 years 5 months
Title
Time to Response
Description
Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better.
Time Frame
Up to 2 years 5 months
Title
Serum Concentrations of Talquetamab
Description
Serum samples will be analyzed to determine concentrations of Talquetamab using validated, specific, and sensitive immunoassay methods.
Time Frame
Up to 2 years 5 months
Title
Serum Concentrations of Teclistamab
Description
Serum samples will be analyzed to determine concentrations of Teclistamab using validated, specific, and sensitive immunoassay methods.
Time Frame
Up to 2 years 5 months
Title
Serum Concentrations of PD-1 Inhibitor
Description
Serum samples will be analyzed to determine concentrations of PD-1 inhibitor using validated, specific, and sensitive immunoassay methods.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Anti-Talquetamab Antibodies
Description
Number of participants with anti-talquetamab antibodies will be reported.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Anti-Teclistamab Antibodies
Description
Number of participants with anti-teclistamab antibodies will be reported.
Time Frame
Up to 2 years 5 months
Title
Number of Participants with Anti-PD-1 Inhibitor Antibodies
Description
Number of participants with anti-PD-1 inhibitor antibodies will be reported.
Time Frame
Up to 2 years 5 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
Participants with relapsed or refractory disease that are not a candidate for available therapy with established clinical benefit
Have measurable disease at screening as defined by at least 1 of the following: a) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL); b) Urine M-protein level >= 200 milligrams (mg) per 24 hours; c) Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams/deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Exclusion Criteria:
Prior antitumor therapy within 21 days prior to the first dose of study treatment (proteasome inhibitor [PI] therapy or radiotherapy within 14 days, immunomodulatory drug (IMiD) agent therapy within 7 days, gene -modified adoptive cell therapy or autologous stem cell transplant within 3 months)
Prior therapy with PD-1 inhibitors, allogeneic stem cell transplant or solid organ transplant
Active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis
Active Central Nervous System (CNS) involvement or exhibition of clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required
Live, attenuated vaccine within 4 weeks before the first dose of study treatment
Non-hematologic toxicity from prior anticancer therapy that has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia [any grade] or peripheral neuropathy to Grade <= 2)
Received a cumulative dose of corticosteroids equivalent to >= 140 milligrams (mg) of prednisone within the 14-day period before the start of study treatment administration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research and Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research and Development LLC
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Individual Site Status
Recruiting
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Vanderbilt - Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Name
CHU de Montpellier, Hopital Saint-Eloi
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nantes hôtel-Dieu
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Poitiers - Hôpital la Milétrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Universitaire du Cancer Toulouse Oncopole
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Carl Gustav Carus Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Name
Hosp. Univ. Germans Trias I Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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 Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
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