Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

Phase 1

Recruiting

• Conditions: Hematological Malignancies
• Interventions: Drug: Talquetamab

• Registration Number: NCT03399799
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 \[Dose Escalation\]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 \[Dose Expansion\]).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2017-12-16
• Study First Submitted: 2017-12-22
• Study First Submitted QC: 2018-01-08
• Study First Posted: 2018-01-16
• Primary Completion: 2022-07-07
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Study Completion: 2025-05-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

• Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Part 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (Beta human chorionic gonadotropin [beta-hCG]) or urine
• Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

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Exclusion Criteria

• Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of Talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (example, coronavirus disease [COVID]-19) by local health authorities are allowed
• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
• Received a cumulative dose of corticosteroids equivalent to greater than or equal to ( >=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose of study drug
• Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2: Dose Expansion (Talquetamab)	Talquetamab	Participants will receive IV infusion or SC injection of Talquetamab at each putative recommended Phase 2 dose(s) (RP2D\[s\]) as determined in Part 1. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment.
Part 1: Dose Escalation (Talquetamab) - Intravenous (IV)	Talquetamab	Participants will receive IV infusion of Talquetamab at minimum anticipated biologic effect level (MABEL)-based starting dose until the completion of the end of treatment visit. Subsequent dose levels will be selected based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and preliminary antitumor activity data. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment.
Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC)	Talquetamab	Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s). All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment.

Primary Outcome Measures

Name	Time	Method
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	From signing of Informed Consent Form (ICF) up to follow up (until 100 days after the last dose of study drug or until the start of subsequent anticancer therapy, if earlier [approximately 2.10 years])	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.
Part 1: Dose-limiting Toxicity (DLT)	Up to Day 28	The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non-hematological toxicity of Grade 3 or higher.

Secondary Outcome Measures

Name	Time	Method
Part 1 and Part 2: Biomarker Assessment	Up to Cycle 7 Day 1 (each cycle of 21-days)	Serum cytokine concentrations will be measured pre- and post-infusion of Talquetamab for biomarker assessment.
Part 1: Number of Participants with Talquetamab Antibodies	Up to 4 weeks	Antibodies to Talquetamab will be assessed to evaluate potential immunogenicity.
Part 2: Time to Response (TTR)	From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years)	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.
Part 1: Talquetamab Serum Concentrations	Up to 4 weeks	Serum concentrations will be calculated for Talquetamab.
Part 2: Progression-Free Survival (PFS)	Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months)	PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.
Part 2: Overall Response Rate (ORR)	Approximately 2.10 years	ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.
Part 2: Duration of Response (DOR)	From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years)	DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of PD, per IMWG criteria.
Part 2: Clinical Benefit Rate (CBR)	Approximately 2.10 years	CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria.

Trial Locations

Locations (13)

Hosp. Univ. Germans Trias I Pujol; 🇪🇸 Badalona, Spain

Hosp Univ Fund Jimenez Diaz; 🇪🇸 Madrid, Spain

Clinica Univ. de Navarra; 🇪🇸 Pamplona, Spain

Hosp. Quiron Madrid Pozuelo; 🇪🇸 Pozuelo de Alarcon, Spain

Hosp Clinico Univ de Salamanca; 🇪🇸 Salamanca, Spain

University of Alabama Birmingham; 🇺🇸 Birmingham, Alabama, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman; 🇧🇪 Liege, Belgium

UMCU; 🇳🇱 Utrecht, Netherlands