TRIMM-3: 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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05338775

Collaborator

(none)

152

Enrollment

Locations

Arms

40.7

Anticipated Duration (Months)

7.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/ Refractory Multiple Myeloma	Drug: Talquetamab Drug: Teclistamab Drug: PD-1 Inhibitor	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

152 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 25, 2022

Anticipated Primary Completion Date :

Sep 21, 2024

Anticipated Study Completion Date :

Oct 15, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Number of Participants with Adverse Events (AEs) [Up to 2 years 5 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 Adverse Events (AEs) by Severity [Up to 2 years 5 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. 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 [Up to 2 years 5 months]
Number of participants with abnormalities in clinical laboratory assessments (serum chemistry and hematology) will be reported.
Number of Participants with Dose-Limiting Toxicity (DLTs) [Up to 2 years 5 months]
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) [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria.
Duration of Response [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
Serum samples will be analyzed to determine concentrations of Talquetamab using validated, specific, and sensitive immunoassay methods.
Serum Concentrations of Teclistamab [Up to 2 years 5 months]
Serum samples will be analyzed to determine concentrations of Teclistamab using validated, specific, and sensitive immunoassay methods.
Serum Concentrations of PD-1 Inhibitor [Up to 2 years 5 months]
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 [Up to 2 years 5 months]
Number of participants with anti-talquetamab antibodies will be reported.
Number of Participants with Anti-Teclistamab Antibodies [Up to 2 years 5 months]
Number of participants with anti-teclistamab antibodies will be reported.
Number of Participants with Anti-PD-1 Inhibitor Antibodies [Up to 2 years 5 months]
Number of participants with anti-PD-1 inhibitor antibodies will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Indiana University	Indianapolis	Indiana	United States	46202
3	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
6	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
7	Vanderbilt - Ingram Cancer Center	Nashville	Tennessee	United States	37232
8	CHU de Montpellier, Hopital Saint-Eloi	Montpellier Cedex 5		France	34295
9	CHU de Nantes hôtel-Dieu	Nantes Cedex 1		France	44093
10	CHU Poitiers - Hôpital la Milétrie	Poitiers		France	86021
11	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse Cedex 9		France	31059
12	Universitätsklinikum Carl Gustav Carus Dresden	Dresden		Germany	01307
13	Universitatsklinikum Freiburg	Freiburg		Germany	79106
14	Universitaetsklinikum Hamburg Eppendorf	Hamburg		Germany	20246
15	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
16	Universitätsklinikum Würzburg	Würzburg		Germany	97080
17	Hosp. Univ. Germans Trias I Pujol	Badalona		Spain	08916
18	Hosp. Univ. Fund. Jimenez Diaz	Madrid		Spain	28040
19	Clinica Univ. de Navarra	Pamplona		Spain	31008
20	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director: Janssen Research and Development, LLC Clinical Trial, Janssen Research and Development LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Research & Development, LLC

ClinicalTrials.gov Identifier:

NCT05338775

Other Study ID Numbers:

CR109168
2021-005073-22
64407564MMY1005

First Posted:

Apr 21, 2022

Last Update Posted:

Aug 15, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Immune Checkpoint Inhibitors

Study Results

No Results Posted as of Aug 15, 2022