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

Relapsed/ Refractory Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05338775
• Other study ID #: CR109168
• Secondary ID: 2021-005073-2264
• Status: Recruiting
• Phase: Phase 1
• Start date: May 25, 2022
• Est. completion date: November 28, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 152
• Est. completion date: November 28, 2025
• Est. primary completion date: September 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/ Refractory Multiple Myeloma

Intervention

Drug:
• Talquetamab
Talquetamab will be administered as a subcutaneous (SC) injection.
• Teclistamab
Teclistamab will be administered as a SC injection.
• PD-1 Inhibitor
The PD-1 inhibitor will be administered as an intravenous injection.

Locations

Country	Name	City	State
France	CHU de Montpellier, Hopital Saint-Eloi	Montpellier Cedex 5
France	CHU de Nantes hotel Dieu	Nantes Cedex 1
France	CHU Poitiers - Hopital la Miletrie	Poitiers
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse Cedex 9
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp Clinico Univ de Salamanca	Salamanca
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	The Blavatnik Family Chelsea Medical Center at Mount Sinai	New York	New York
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with Anti-Talquetamab Antibodies	Number of participants with anti-talquetamab antibodies will be reported.	Up to 2 years 5 months
Secondary	Number of Participants with Anti-Teclistamab Antibodies	Number of participants with anti-teclistamab antibodies will be reported.	Up to 2 years 5 months
Secondary	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