A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT04586426
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: May 21, 2021
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

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 will describe the combination doses and schedules of talquetamab and teclistamab to be pursued in Phase 2.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Talquetamab; Drug: Teclistamab	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. 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. 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 years. 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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 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 1, 2021
• Estimated Study Completion Date: June 16, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Step-up Dosing and Dose Escalation; Participant will receive step-up doses of talquetamab and teclistamab prior to Cycle 1 Day 1; thereafter, the participant will receive treatment doses of talquetamab and teclistamab in 28-day cycles.	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
Experimental: Part 2: Dose Expansion; Participants will receive treatment doses (combination of talquetamab and teclistamab) 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

Outcome Measures

Primary Outcome Measures :

1. Part 1: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Up to 1 year ]
   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 ]
   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 ]
   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 ]
   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 ]
   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 ]
   Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method.
3. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Talquetamab [ Time Frame: Up to 1 year ]
   Number of participants with anti-drug antibodies to talquetamab will be assessed.
4. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Teclistamab [ Time Frame: Up to 1 year ]
   Number of Participants with anti-drug antibodies to teclistamab will be assessed.
5. Part 1 and Part 2: Overall Response Rate (ORR) [ Time Frame: Up to 1 year ]
   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.
6. Part 1 and Part 2: Very Good Partial Response (VGPR) or Better Response Rate [ Time Frame: Up to 1 year ]
   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.
7. Part 1 and Part 2: Complete Response (CR) or Better Response Rate [ Time Frame: Up to 1 year ]
   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.
8. Part 1 and Part 2: Stringent Complete Response (sCR) Rate [ Time Frame: Up to 1 year ]
   sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria.
9. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Up to 1 year ]
   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.
10. Part 1 and Part 2: Time to Response [ Time Frame: Up to 1 year ]
    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

• 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. 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
• 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 talquetamab, teclistamab, or their excipients

Contacts and Locations

Contacts

Contact: Study Contact; 844-434-4210; JNJ.CT@sylogent.com

Locations

Canada, Alberta

Alberta Health Services; Not yet recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Quebec

McGill University Health Centre; Not yet 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

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

More Information

Additional Information:

To learn how to participate in this trial please click here. 

• 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
• Last Update Posted: May 21, 2021
• Last Verified: May 2021

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

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

Additional relevant MeSH terms:

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