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)

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 1

Conditions: Relapsed/ Refractory Multiple Myeloma

Treatments: Drug: PD-1 Inhibitor; Drug: Talquetamab; Drug: Teclistamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05338775

2022-502681-24-00 (Registry Identifier)

64407564MMY1005 (Other Identifier)

CR109168

2021-005073-22 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 74 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

Part 1: Dose Escalation

Experimental group

Description:

Participants will receive either talquetamab (treatment regimen A) or teclistamab (treatment regimen B) with a PD-1 inhibitor biweekly.

Treatment:

Drug: Teclistamab

Drug: Talquetamab

Drug: PD-1 Inhibitor

Part 2: Dose Expansion

Experimental group

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.

Treatment:

Drug: Teclistamab

Drug: Talquetamab

Drug: PD-1 Inhibitor