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

Study Overview
=================
Brief Summary
-----------------
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).

Detailed Description
-----------------
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 of 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a post-treatment follow-up phase (until the end of study unless the participant has died, is lost to follow up or has withdrawn consent).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.

Official Title
-----------------
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

Conditions
-----------------
Hematological Malignancies

Intervention / Treatment
-----------------
* Drug: Talquetamab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria Part 3: Measurable disease cohort A, cohort B, cohort C, and cohort D: multiple myeloma must be measurable by central laboratory assessment Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 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 [hCG]) or urine Willing and able to adhere to the prohibitions and restrictions specified in this protocol Exclusion Criteria: Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B and Cohort D: T cell redirection therapy within 3 months 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 >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication) Stroke or seizure within 6 months prior to signing the informed consent form (ICF)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 3: Cohort A (Talquetamab)<br>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. | Drug: Talquetamab<br>* Talquetamab will be administered SC until disease progression.<br>* Other names: JNJ-64407564;|
| Experimental: Part 3: Cohort B (Talquetamab)<br>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. | Drug: Talquetamab<br>* Talquetamab will be administered SC until disease progression.<br>* Other names: JNJ-64407564;|
| Experimental: Part 3: Cohort C (Talquetamab)<br>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. | Drug: Talquetamab<br>* Talquetamab will be administered SC until disease progression.<br>* Other names: JNJ-64407564;|
| Experimental: Part 3: Cohort D (Talquetamab)<br>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. | Drug: Talquetamab<br>* Talquetamab will be administered SC until disease progression.<br>* Other names: JNJ-64407564;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | 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. | Up to 2 years and 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | 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. | Up to 2 years and 10 months | 
| Very Good Partial Response (VGPR) or Better Rate | VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria. | Up to 2 years and 10 months | 
| Complete Response (CR) or Better Rate | CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria. | Up to 2 years and 10 months | 
| Stringent Complete Response (sCR) Rate | sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria. | Up to 2 years and 10 months | 
| Time to Response (TTR) | 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. | Up to 2 years and 10 months | 
| Progression-Free Survival (PFS) | 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. | Up to 2 years and 10 months | 
| Overall Survival (OS) | OS is defined as the time from the date of first dose of study drug to the date of the participant's death. | Up to 2 years and 10 months | 
| Minimal Residual Disease (MRD) Negative Rate | 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. | Up to 2 years and 10 months | 
| Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | 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. | Up to 2 years and 10 months | 
| Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | 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. | Up to 2 years and 10 months | 
| Number of Participants with AEs by Severity | 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. | Up to 2 years and 10 months | 
| Number of Participants with Abnormalities in Clinical Laboratory Values | Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported. | Up to 2 years and 10 months | 
| Serum Concentration of Talquetamab | Serum samples will be analyzed to determine concentrations of talquetamab. | Up to 2 years and 10 months | 
| Number of Participants with Talquetamab Antibodies | Antibodies to talquetamab will be assessed to evaluate potential immunogenicity. | Up to 2 years and 10 months | 
| Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) | 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. | Baseline up to 2 years and 10 months | 
| Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) | 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. | Baseline up to 2 years and 10 months | 
| Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) | 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). | Baseline up to 2 years and 10 months | 
| Overall Response Rate (ORR) in Participants with High-risk Molecular Features | 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. | Up to 2 years and 10 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Myeloma