The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

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

Hematological Malignancies

Hematologic Neoplasms

Hematologic Malignancies

Blood Cancer

Talquetamab

A Phase 1/2, 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

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.

DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria, or death due to PD, whichever occurs first.

VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.

CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.

sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.

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.

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.

OS is defined as the time from the date of first dose of study drug to the date of the participant's death.

MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.

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.

An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). 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.

Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.

Serum samples will be analyzed to determine concentrations of talquetamab.

Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.

The EORTC- QLQ-Core-30 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("past week") and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.

The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).

ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.

Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the long-term extension (LTE) and will continue to receive study treatment.

Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Cohort D will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants in this cohort will receive tocilizumab prophylaxis for cytokine release syndrome (CRS) including all outpatient dosing. Participants will transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Cohort E will enroll participants with multiple myeloma who have previously received at least 1 proteasome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-cluster of differentiation 38 (CD38) monoclonal antibody.

Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants will receive tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as possible transition to outpatient priming dosing transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

The purpose of this study is to evaluate the efficacy of talquetamab in participants with
      relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions,
      increased susceptibility to infections, hypercalcemia, and renal failure. Talquetamab is a
      humanized immunoglobulin G4 proline, alanine, alanine (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). 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 (30 days (+ 7 days)] visit); and a post-treatment follow-up
      phase (until the end of study unless the participant has died, is lost to follow up or has
      withdrawn consent). Total duration of study is up to 2 years (after the last participant
      receives their first dose). Safety, pharmacokinetics (PK), laboratory tests, and
      questionnaire will be assessed at specified time points during this study. Participants
      safety and study conduct will be monitored throughout the study. The corresponding study
      (NCT03399799) is the Phase 1 part of the study and TALMMY1001- Part 3 is the Phase 2 part of
      the study.

University of Alabama Birmingham

University of Arkansas for Medical Sciences

City of Hope

Emory University - Winship Cancer Institute

University of Chicago

Norton Cancer Institute

University of Michigan Health System

Washington University School of Medicine

NYU Langone Health

Mount Sinai Medical Center

University of Rochester Medical Center

Providence Portland Medical Center

Sarah Cannon Research Institute

UCL - Saint Luc

UZ Antwerpen

UZ Leuven

CHU de Liège - Domaine Universitaire du Sart Tilman

Peking University Third Hospital

Sun Yat-Sen University Cancer Center

First affiliated Hospital of Zhejiang University

First Affiliated Hospital, SooChow University

Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science

First Affiliated Hospital of Xi'an Jiaotong University School of Medicine

CHU Henri Mondor

CHU de Montpellier, Hopital Saint-Eloi

C.H.U. Hotel Dieu - France

CHU de Bordeaux - Hospital Haut-Leveque

Centre hospitalier Lyon-Sud

Pôle IUC Oncopole CHU

Charite Campus Benjamin Franklin

Universitaetsklinikum Heidelberg

Universitaetsklinikum Muenster

Universitätsklinikum Würzburg

Rambam Medical Center

Carmel Medical Center

Hadassah Medical Center

Sheba Medical Center

Tel Aviv Sourasky Medical Center

Kameda General Hospital

Fukuoka University Hospital

Ogaki Municipal Hospital

Teine Keijinkai Hospital

Kobe City Medical Center General Hospital

Dokkyo Medical University Saitama Medical Center

Kumamoto University Hospital

Kurashiki Central Hospital

National Hospital Organization Matsumoto Medical Center

National Hospital Organization Okayama Medical Center

Japanese Red Cross Osaka Hospital

Hiroshima West Medical Center

Iwate Medical University Hospital

Chonnam National University Hwasun Hospital

Seoul National University Hospital

Severance Hospital, Yonsei University Health System

Asan Medical Center

Samsung Medical Center

The Catholic University of Korea Seoul St. Mary's Hospital

VU Medisch Centrum

UMCU

Uniwersyteckie Centrum Kliniczne

Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach

Uniwersytecki Szpital Kliniczny w Poznaniu

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Hosp. Univ. Germans Trias I Pujol

Hosp. Univ. Vall D Hebron

Inst. Cat. Doncologia-H Duran I Reynals

Hosp. Univ. Fund. Jimenez Diaz

Hosp. Univ. 12 de Octubre

Hosp. Univ. Virgen de La Arrixaca

Clinica Univ. de Navarra

Hosp. Quiron Madrid Pozuelo

Hosp. Clinico Univ. de Salamanca

Hosp. Univ. Marques de Valdecilla

Hosp. Virgen Del Rocio

Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

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

Trials at a glance

Trials at a glance

Eligibility criteria