Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)

• ClinicalTrials.gov Identifier: NCT03399799
• Recruitment Status: Recruiting
• First Posted: January 16, 2018
• Last Update Posted: April 25, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: December 22, 2017
• First Posted Date: January 16, 2018
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: December 16, 2017
• Actual Primary Completion Date: July 7, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2018)

• Part 1: Dose-limiting Toxicity (DLT) [ Time Frame: 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.
• Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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.

Original Primary Outcome Measures (submitted: January 8, 2018)

• Dose-limiting Toxicity (DLT) [ Time Frame: 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.
• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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) ]
  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.

Current Secondary Outcome Measures (submitted: March 15, 2023)

• Part 1: Talquetamab Serum Concentrations [ Time Frame: Up to 4 weeks ]
  Serum concentrations will be calculated for Talquetamab.
• Part 1 and Part 2: Biomarker Assessment [ Time Frame: 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 [ Time Frame: Up to 4 weeks ]
  Antibodies to Talquetamab will be assessed to evaluate potential immunogenicity.
• Part 2: Overall Response Rate (ORR) [ Time Frame: 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: Clinical Benefit Rate (CBR) [ Time Frame: 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.
• Part 2: Duration of Response (DOR) [ Time Frame: 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: Time to Response (TTR) [ Time Frame: 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 2: Progression-Free Survival (PFS) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: January 8, 2018)

• JNJ-64407564 Serum Concentrations [ Time Frame: Up to 8 weeks ]
  Serum concentrations will be calculated for JNJ-64407564.
• Biomarker Assessment [ Time Frame: Up to Cycle 7, Day 1 ]
  Serum cytokine concentrations will be measured pre- and post-infusion of JNJ-64407564 for biomarker assessment.
• Number of Participants with JNJ-64407564 Antibodies [ Time Frame: Up to 8 weeks ]
  Antibodies to JNJ-64407564 will be assessed to evaluate potential immunogenicity.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma
• 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
• 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: 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hematological Malignancies

Intervention

Drug: Talquetamab

Participants will receive IV infusion or SC injection of Talquetamab.

Study Arms

• Experimental: Part 1: Dose Escalation (Talquetamab) - Intravenous (IV)
  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.
  Intervention: Drug: Talquetamab
• Experimental: Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC)
  Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s).
  Intervention: Drug: Talquetamab
• Experimental: Part 2: Dose Expansion (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.
  Intervention: Drug: Talquetamab

• Publications *: Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 15, 2023): 320
• Original Estimated Enrollment (submitted: January 8, 2018): 60
• Estimated Study Completion Date: April 30, 2025
• Actual Primary Completion Date: July 7, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Belgium, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT03399799
• Other Study ID Numbers: CR108404; 2017-002400-26 ( EudraCT Number ); 64407564MMY1001 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024