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A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (RedirecTT-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04586426
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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Brief Summary:
The purpose of this study is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1) and to characterize the safety of the RP2R(s) for the study treatment (Part 2). The RP2R(s) will describe the combination doses and schedules of (tal+tec+dara) the treatment combinations to be pursued in Phase 2.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Talquetamab Drug: Teclistamab Drug: Daratumumab Phase 1

Detailed Description:
Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Talquetamab is a humanized IgG4PAA bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). Teclistamab is a humanized IgG4PAA bispecific antibody designed to target B cell maturation antigen (BCMA) and the CD3 molecule found on T cells. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Rationale for combining talquetamab and teclistamab is that, these agents promote the activation of T cells and induce myeloma cell lysis mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells and daratumumab induces lysis of CD38-expressing tumor cells by a number of mechanisms, including complement-dependent cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), through activation of complement proteins, natural killer (NK) cells, and macrophages, respectively. This study consists 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as last study assessment for last participant in study. Total duration of study is up to 1 year and 6 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : December 15, 2020
Estimated Primary Completion Date : November 16, 2023
Estimated Study Completion Date : May 28, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses.
 Drug: Talquetamab
Talquetamab will be administered by subcutaneous (SC) injection.
Other Name: JNJ-64407564

Drug: Teclistamab
Teclistamab will be administered by SC injection.
Other Name: JNJ-64007957

Drug: Daratumumab
Daratumumab will be administered by SC injection.
Experimental: Part 2: Dose Expansion
Participants will receive treatment doses (combination of tal+tec and dara+tal+tec regimens) which will be determined by the RP2R(s) of the study treatment identified in Part 1.
 Drug: Talquetamab
Talquetamab will be administered by subcutaneous (SC) injection.
Other Name: JNJ-64407564

Drug: Teclistamab
Teclistamab will be administered by SC injection.
Other Name: JNJ-64007957

Drug: Daratumumab
Daratumumab will be administered by SC injection.


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 1 year and 6 months ]
    The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.

  2. Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) [ Time Frame: Up to 1 year and 6 months ]
    Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.

  3. Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 1 year and 6 months ]
    An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product.

  4. Part 2: Number of Participants with Adverse Events and SAEs by Severity [ Time Frame: Up to 1 year and 6 months ]
    Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.


Secondary Outcome Measures :
  1. Part 1 and Part 2: Serum Concentration of Talquetamab [ Time Frame: Up to 1 year and 6 months ]
    Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive immunoassay method.

  2. Part 1 and Part 2: Serum Concentration of Teclistamab [ Time Frame: Up to 1 year and 6 months ]
    Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method.

  3. Part 1 and Part 2: Serum Concentration of Daratumumab [ Time Frame: Up to 1 year and 6 months ]
    Serum samples will be analyzed to determine concentrations of daratumumab using a validated, specific, and sensitive immunoassay method.

  4. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Talquetamab [ Time Frame: Up to 1 year and 6 months ]
    Number of participants with anti-drug antibodies to talquetamab will be assessed.

  5. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Teclistamab [ Time Frame: Up to 1 year and 6 months ]
    Number of Participants with anti-drug antibodies to teclistamab will be assessed.

  6. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab [ Time Frame: Up to 1 year and 6 months ]
    Number of Participants with anti-drug antibodies to daratumumab will be assessed.

  7. Part 1 and Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 1 year and 6 months ]
    ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.

  8. Part 1 and Part 2: Very Good Partial Response (VGPR) or Better Response Rate [ Time Frame: Up to 1 year and 6 months ]
    VGPR or better response rate (sCR+CR+VGPR) is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria.

  9. Part 1 and Part 2: Complete Response (CR) or Better Response Rate [ Time Frame: Up to 1 year and 6 months ]
    CR or better response rate (sCR+CR) is defined as the percentage of participants who achieve a CR or better response according to the IMWG criteria.

  10. Part 1 and Part 2: Stringent Complete Response (sCR) Rate [ Time Frame: Up to 1 year and 6 months ]
    sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria.

  11. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Up to 1 year and 6 months ]
    DOR will be calculated among responders (with PR or better) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.

  12. Part 1 and Part 2: Time to Response [ Time Frame: Up to 1 year and 6 months ]
    Time to response 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria based on documented medical history
  • Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy (except as noted in point 'a' and 'b'). (a) For cohorts without daratumumab, prior lines of therapy must include a proteasome inhibitor (PI) (example, bortezomib, carfilzomib, ixazomib), an immunomodulatory drug (IMiD) (example, thalidomide, lenalidomide, pomalidomide), and an anti-CD38 therapy (example, daratumumab, isatuximab) in any order. (b) For cohorts with daratumumab, prior lines of therapy must include a PI (example, bortezomib, carfilzomib, ixazomib) and an IMiD (example, thalidomide, lenalidomide, pomalidomide). Treatment with an anti-CD38 therapy (example, daratumumab) is allowed greater than equal to (>=) 90 days prior to study treatment if the participant did not discontinue prior treatment due to adverse events related to anti-CD38 therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration
  • Women of childbearing potential must have a negative highly-sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (less than [<] 5 international units per milliliter [IU/mL]) at screening and a negative urine or serum pregnancy test within 24 hours prior to the first step-up dose and the first dose of each treatment cycle
  • Men must agree not to donate sperm for reproduction during the study and for a minimum 100 days after receiving the last dose of study treatment

Exclusion Criteria:

  • Prior anticancer therapy as follows: a) targeted therapy, epigenetic therapy, or treatment with an investigational treatment or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less; b) monoclonal antibody treatment for multiple myeloma within 21 days; c) cytotoxic therapy within 21 days; d) proteasome inhibitor (PI) therapy within 14 days; e) immunomodulatory drug (IMiD) therapy within 7 days; f) radiotherapy within 21 days. However, if the radiation portal covered less than or equal to (<=) of the bone marrow reserve, the participant is eligible irrespective of the end date of radiotherapy; g) gene modified adoptive cell therapy (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months
  • A cumulative dose of corticosteroids equivalent to more than or equal to (>=) 140 milligram (mg) of prednisone within 14 days
  • Live, attenuated vaccine within 4 weeks prior to first dose of study drug unless approved by sponsor
  • Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV RNA testing
  • Known allergies, hypersensitivity, or intolerance to daratumumab, talquetamab, teclistamab, or their excipients
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586426


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

Locations
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Canada, Alberta
Alberta Health Services Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Quebec
McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H4A 3J1
Israel
Hadassah Medical Center Recruiting
Jerusalem, Israel, 91120
Sheba Medical Center Recruiting
Ramat Gan, Israel, 52621
Tel-Aviv Sourasky Medical Center Recruiting
Tel-Aviv, Israel, 64239
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 06591
Spain
Hosp. Univ. Germans Trias I Pujol Recruiting
Badalona, Spain, 08916
Hosp. Univ. Fund. Jimenez Diaz Recruiting
Madrid, Spain, 28040
Clinica Univ. de Navarra Recruiting
Pamplona, Spain, 31008
Hosp. Clinico Univ. de Salamanca Recruiting
Salamanca, Spain, 37007
Hosp. Univ. Marques de Valdecilla Recruiting
Santander, Spain, 39008
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04586426    
Other Study ID Numbers: CR108901
2019-004124-38 ( EudraCT Number )
64007957MMY1003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: August 15, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
 Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Daratumumab
Antineoplastic Agents