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 (TRIMM-3)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/ Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Talquetamab; Drug: Teclistamab; Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• France
  • Montpellier Cedex 5, France, 34295
    • Recruiting
    • CHU de Montpellier, Hopital Saint-Eloi
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • CHU de Nantes hotel Dieu
  • Poitiers, France, 86021
    • Recruiting
    • CHU Poitiers - Hôpital la Milétrie
  • Toulouse Cedex 9, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Hamburg, Germany, 20246
    • Recruiting
    • Universitaetsklinikum Hamburg Eppendorf
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
  • Wuerzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Hosp. Univ. Germans Trias I Pujol
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp. Univ. Fund. Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt - Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly.	Drug: Talquetamab; Talquetamab will be administered as a subcutaneous (SC) injection.; Drug: Teclistamab; Teclistamab will be administered as a SC injection.; Drug: PD-1 Inhibitor; The PD-1 inhibitor will be administered as an intravenous injection.
Experimental: Part 2: Dose Expansion; Participants will receive either treatment regimen A or treatment regimen B with a PD-1 inhibitor at the dose levels identified in Part 1.	Drug: Talquetamab; Talquetamab will be administered as a subcutaneous (SC) injection.; Drug: Teclistamab; Teclistamab will be administered as a SC injection.; Drug: PD-1 Inhibitor; The PD-1 inhibitor will be administered as an intravenous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months
Stringent Complete Response (sCR) Rate	sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria.	Up to 2 years 5 months
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.	Up to 2 years 5 months
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.	Up to 2 years 5 months
Serum Concentrations of Talquetamab	Serum samples will be analyzed to determine concentrations of Talquetamab using validated, specific, and sensitive immunoassay methods.	Up to 2 years 5 months
Serum Concentrations of Teclistamab	Serum samples will be analyzed to determine concentrations of Teclistamab using validated, specific, and sensitive immunoassay methods.	Up to 2 years 5 months
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.	Up to 2 years 5 months
Number of Participants with Anti-Talquetamab Antibodies	Number of participants with anti-talquetamab antibodies will be reported.	Up to 2 years 5 months
Number of Participants with Anti-Teclistamab Antibodies	Number of participants with anti-teclistamab antibodies will be reported.	Up to 2 years 5 months
Number of Participants with Anti-PD-1 Inhibitor Antibodies	Number of participants with anti-PD-1 inhibitor antibodies will be reported.	Up to 2 years 5 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research and Development, LLC Clinical Trial, Janssen Research and Development LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): September 21, 2024
• Study Completion (Estimated): November 28, 2025

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CR109168; 2021-005073-22 (EudraCT Number); 64407564MMY1005 (Other Identifier: Janssen Research and Development, LLC); 2022-502681-24-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No