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

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ClinicalTrials.gov Identifier: NCT03399799
Recruitment Status : Recruiting
First Posted : January 16, 2018
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE December 22, 2017
First Posted Date  ICMJE January 16, 2018
Last Update Posted Date April 9, 2021
Actual Study Start Date  ICMJE December 16, 2017
Estimated Primary Completion Date April 3, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2020)
  • Part 1: Talquetamab Serum Concentrations [ Time Frame: Up to 8 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 8 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  ICMJE
 (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  ICMJE Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematological Malignancies
Intervention  ICMJE Drug: Talquetamab
Participants will receive IV infusion or SC injection of Talquetamab.
Study Arms  ICMJE
  • 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, Mendonça 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2020)
245
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2018)
60
Estimated Study Completion Date  ICMJE November 29, 2024
Estimated Primary Completion Date April 3, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  • Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the product manufacturer prior to the first dose, during treatment, or within 100 days of the last dose of Talquetamab
  • 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Belgium,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03399799
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP