RecruitingPhase 2ACTRN12625000438459

A Centralized Platform study for Functional High Risk Multiple Myeloma: Domain 1

A Centralized Platform study for Functional High Risk Multiple Myeloma: Domain 1 - Talquetamab and Teclistamab

Sponsor

Australasian Myeloma Research Consortium

Enrollment

20 participants

Start Date

Jun 11, 2025

Study Type

Interventional

Conditions

Relapsed refractory myeloma Myeloma

Summary

The purpose of this platform study is to assess the efficacy of teclistamab and talquetamab for patients who have functional high-risk disease, defined as relapsing or refractory within 18 months of first-line myeloma treatment. Patients who have functional high-risk disease currently do not have optimal treatments available via the Pharmaceutical Benefits Scheme and have poorer outcomes compared to myeloma patients who are not considered functional high-risk. Who is it for? You may be eligible for this study if you are male or female aged 18 years or older, have a documented diagnosis of multiple myeloma and have relapsed within 18 months following initiation of first-line therapy and require treatment. Study details Participants who choose to enrol in this domain of the ZEPFHR-MM platform trial will be administered two cancer treatment drugs (via an injection into the skin) for up to 24 treatment cycles. Each treatment cycle will continue for 28 days following the first drug dose and participants will be monitored to determine whether they are responding to the treatment or not. It is hoped this research will determine whether the combination of teclistamab and talquetamab cancer treatments is effective at slowing and/or stopping disease progression in patients with relapsing or refractory multiple myeloma. If this treatment is shown to be effective, it may be offered to a larger number of patients with multiple myeloma in the future.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria16

Age >= 18 years of age.
Able to provide written consent.
Documented diagnosis of MM with measurable disease as define by any of the following
Serum M-component greater than 5 g per L and/or
Urine M-component greater than200 mg per 24 h, and/or
Involved serum free light chain level greater than 100mg per L.
Patients who do not meet these criteria but have biopsy proven extra-medullary disease (extra-osseous plasmacytoma that is not contiguous with an osseous plasmacytoma) that can undergo response evaluation with serial PET-CT are considered to have measurable disease.
Documented evidence of progressive disease within 18 months of commencing front-line therapy for newly diagnosed MM according to IMWG response criteria
Patients must have received only 1 prior therapy consisting of an IMID or PI-based induction regimen with or without high dose melphalan conditioned autologous stem cell transplant +/- lenalidomide maintenance.
No contraindication to the use of any of the study drugs and able to comply with trial requirements.
Adequate liver function (total bilirubin less than 2.0x upper limit of normal (ULN), alanine aminotransferase less than 5.0x ULN) unless considered secondary to MM.
Absolute neutrophil count greater than or equal to 1.0 x 10^9 per L. Granulocyte colony-stimulating factor (G-CSF) therapy is permitted on study.
Platelet count greater than or equal to 50 x 10^9 per L (greater than or equal to 30 x 10^9 per L if MM involvement in the marrow is greater than 50 per cent), patients should not have received platelet transfusions within 7 days of the screening platelet count.
Hb greater than or equal to 80 g per L, red cell transfusions as per institutional protocol are allowed.
Has provided written informed consent.
Women of childbearing potential participants must not become pregnant while on study; male participants must not father children while on study

Exclusion Criteria13

Patients who have had myocardial infarction within 6 months prior to enrolment, or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators’ opinion, potentially interfere with the completion of treatment according to this protocol.
Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency virus positivity. Patients with latent TB can proceed on study provided adequate prophylaxis has been commenced.
Known autoimmune disease requiring ongoing immunosuppression
Women who are pregnant or lactating. Women of child-bearing potential must have a negative pregnancy test (minimum sensitivity of at least 25 mIU per mL) at Screening.
Active malignancy with the exception of any of the following:
o Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer.
o Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for greater than 2 years.
o Stage 1 prostate cancer that does not require treatment.
o Any other cancer from which the subject has been disease-free for greater than 2 years.
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Participation in other clinical trials for the treatment of MM, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial
Patients with pre-existing venous access, in the form of a PICC line or PORT (due to higher risk of bloodborne infections) that has not been replaced within the last 3 months and/or has a documented history of previous bacteraemia or potential line-related sepsis.

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Interventions

Each treatment cycle is 28-days. Maximum number of cycles is 24. Treatment is administered by hospital staff. [Talquetamab] - To be given subcutaneously - Cycle 1 Day 1 -0.01mg per kg - Cycle 1 D

Each treatment cycle is 28-days. Maximum number of cycles is 24. Treatment is administered by hospital staff. [Talquetamab] - To be given subcutaneously - Cycle 1 Day 1 -0.01mg per kg - Cycle 1 Day 4 - 0.06mg per kg - Cycle 1 Day 8 - 0.4mg per kg - Cycle 1 Day 15 - 0.8mg per kg - Cycle 2 to 24 - Day 1 and 15 - 0.8mg per kg - If a participant achieves a 'Very Good Partial Response' (VGPR) as per the International Myeloma Working Group (IMWG) Response Criteria from Cycle 5 onwards- 0.8mg per kg on Day 1 of each subsequent until end of Cycle 24 - If a participant achieves a 'Partial Response' (VGPR) as per the International Myeloma Working Group (IMWG) Response Criteria from Cycle 7 onwards: 0.8mg per kg on Day 1 of each subsequent until end of Cycle 24 - Cycle 7 to 24 - If participant has a 'Partial Response' (PR) as per the (IMWG) Response Criteria Day 1 - 0.8mg per kg [Teclistamab] - To be given subcutaneously - Cycle 1 Day 1 - 0.06mg/kg - Cycle 1 Day 4 - 0.3mg/kg - Cycle 1 Day 8 and 15 - 1.5mg/kg - Cycle 2 to 24, Day 1 - 3.0mg/kg Monitoring of adherence: Interventions will be administered by hospital staff and recorded in dose logs and other medical relevant medical record