TALQUETAMAB for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- ≥18 years of age"}
• {"criterion_text":"- Documented initial diagnosis of multiple myeloma according to IMWG diagnostic a criteria"}
• {"criterion_text":"- Part 1: - Subjects with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: - Subjects 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 ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin 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%. Part 3: Measurable disease Cohort A, B and Cohort C: Multiple myeloma must be measurable by central laboratory assessment: - Serum M-protein level ≥1.0 g/dL or urine Mprotein level ≥200 mg/24 hours; 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%. Cohort E: Multiple myeloma must be measurable by local laboratory assessment: - Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or - Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio. Prior treatment - Cohort A and Cohort C: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have not been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. - Cohort B: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies. Cohort D: have previously received ≥3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody regardless of exposure to prior T cell redirection therapies such as CAR- T or bispecific antibodies. Cohort E: have previously received at least one PI, one IMiD, and one anti-CD38 monoclonal antibody regardless of exposure to prior T-cell redirection therapies such as CAR-T or bispecific antibodies. All Cohorts: Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease was the best response to the line of therapy. Subject must have documented evidence of progressive disease based on investigator’s determination of response by the IMWG 2016 criteria on or within 12 months of their last line of therapy*. Also, subjects with documented evidence of progressive disease within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible. *Criteria for progressive disease on or within 12 months of therapy does not apply to patients with CAR-T as last line of therapy (ie, Cohort B, D, and E)."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 for Parts 1 and 2 and 0-2 for Part 3 of the study"}
• {"criterion_text":"- Pretreatment clinical laboratory values meeting the predefined criteria during the Screening Phase"}

Exclusion criteria

• {"criterion_text":"- Prior Grade 3 CRS or higher related to any T cell redirection (eg, CD-3 redirection technology or CAR-T cell therapy) or any prior GPRC5D targeting therapy"}
• {"criterion_text":"- Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation."}
• {"criterion_text":"- Known allergies, hypersensitivity, or intolerance to talquetamab or its excipients."}
• {"criterion_text":"- Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study drug administration. (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate)."}
• {"criterion_text":"- Any potential subject who meets any of the following criteria will be excluded from participating in Part 3: Stroke or seizure within 6 months prior to signing the ICF The following cardiac conditions: - New York Heart Association Stage III or IV congestive heart failure - Myocardial infarction or coronary artery bypass graft (CABG) ≤6 months prior to enrollment - History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration - History of severe non-ischemic cardiomyopathy. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study."}
• {"criterion_text":"- Prior antitumor therapy as follows, prior to the first dose of study drug: - Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells [CAR-T], natural killer [NK] cells) within 3 months. - Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. - Monoclonal antibody treatment for multiple myeloma within 21 days. - Cytotoxic therapy within 21 days. - Proteasome inhibitor therapy within 14 days. - Immunomodulatory agent therapy within 7 days. - Radiotherapy within 14 days. However, if palliative focal radiation is used, the subject is eligible irrespective of the end date of radiotherapy. Part 3 only: - Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. - Cohort B, D, and E: T cell redirection therapy within 3 months"}
• {"criterion_text":"- Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy"}
• {"criterion_text":"- Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)."}
• {"criterion_text":"- Received either of the following: - An allogenic stem cell transplant within 6 months before first dose of study drug. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft versus host disease (GVHD). - An autologous stem cell transplant ≤12 weeks before first dose of study drug"}
• {"criterion_text":"- Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma."}
• {"criterion_text":"- Plasma cell leukemia (>2.0 x 10 to the 9th/L plasma cells by standard differential), Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes), or primary amyloid light chain amyloidosis."}
• {"criterion_text":"- Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome."}
• {"criterion_text":"- Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status. Active Hepatitis C infection as measured by positive HCV-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing."}

Primary endpoints

• {"endpoint_text":"- Part 1 and Part 2: Frequency and type of DLT; frequency and severity of adverse events, serious adverse events, and laboratory abnormalities","definition_or_measurement_approach":"Not further specified in Part I entry beyond monitoring frequency and severity of DLTs, AEs, SAEs and laboratory abnormalities."}
• {"endpoint_text":"- Part 3: ORR (PR or better) as defined by the IMWG criteria based on review by the IRC","definition_or_measurement_approach":"Objective response rate (partial response or better) defined by IMWG 2016 criteria and assessed by Independent Review Committee (IRC)."}
• {"endpoint_text":"- Occurrence and severity of TEAEs, serious TEAEs, adverse events of clinical interest, and ORR [PR or better], DOR, VGPR or better/CR or better/sCR, TTR, PFS, and OS.","definition_or_measurement_approach":"Safety assessed by frequency and severity of treatment-emergent AEs (TEAEs) and serious TEAEs. Efficacy measures include ORR (PR or better), duration of response (DOR), very good partial response (VGPR) or better, complete response (CR) or better, stringent CR (sCR), time to response (TTR), progression-free survival (PFS), and overall survival (OS) as defined by standard oncologic/IMWG criteria."}

Germany

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

526

Number Of Sites

3

Number Of Participants

27

Netherlands

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

524

Number Of Sites

2

Number Of Participants

27

Belgium

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

25-07-2025

Processing Time Days

533

Number Of Sites

4

Number Of Participants

21

France

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

526

Number Of Sites

6

Number Of Participants

56

Spain

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

21-07-2025

Processing Time Days

529

Number Of Sites

11

Number Of Participants

120

Poland

Earliest CTIS Part Ii Submission Date

08-02-2024

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

526

Number Of Sites

4

Number Of Participants

40

Primary sponsor

Full Name

Janssen - Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Smithers PDS LLC

Responsibilities

PK analysis

Name

Icon Development Solutions LLC

Responsibilities

PK analysis

Name

Navigate Biopharma Services Inc.

Name

Labcorp

Name

Certara USA Inc.

Name

Adaptive Biotechnologies Corp.

Name

Cellcarta Biosciences Inc.

Third parties

• {"country":"United States","full_name":"Smithers PDS LLC","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}