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

Hematological Malignancies Clinical Trial

— MonumenTAL-1  

Official title:

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03399799
• Other study ID #: CR108404
• Secondary ID: 2017-002400-2664
• Status: Recruiting
• Phase: Phase 1
• Start date: December 16, 2017
• Est. completion date: April 30, 2025

Study information

• Verified date: May 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 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]).

Description:

The study will be conducted in 2 parts: dose escalation and dose expansion. The study will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of Talquetamab administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as the last study assessment for the last participant in the study. Study record NCT04634552 is Phase 2 part of this study and study record NCT03399799 is Phase 1 part of this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: April 30, 2025
• Est. primary completion date: July 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Multiple Myeloma

Intervention

Drug:
• Talquetamab
Participants will receive IV infusion or SC injection of Talquetamab.

Locations

Country	Name	City	State
Belgium	Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman	Liege
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	UMCU	Utrecht
Spain	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, Madrid
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	City of Hope	Duarte	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Dose-limiting Toxicity (DLT)	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.	Up to Day 28
Primary	Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	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.	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])
Secondary	Part 1: Talquetamab Serum Concentrations	Serum concentrations will be calculated for Talquetamab.	Up to 4 weeks
Secondary	Part 1 and Part 2: Biomarker Assessment	Serum cytokine concentrations will be measured pre- and post-infusion of Talquetamab for biomarker assessment.	Up to Cycle 7 Day 1 (each cycle of 21-days)
Secondary	Part 1: Number of Participants with Talquetamab Antibodies	Antibodies to Talquetamab will be assessed to evaluate potential immunogenicity.	Up to 4 weeks
Secondary	Part 2: Overall Response Rate (ORR)	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.	Approximately 2.10 years
Secondary	Part 2: Clinical Benefit Rate (CBR)	CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria.	Approximately 2.10 years
Secondary	Part 2: Duration of Response (DOR)	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.	From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years)
Secondary	Part 2: Time to Response (TTR)	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.	From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years)
Secondary	Part 2: Progression-Free Survival (PFS)	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.	Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months)

External Links

•   A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma