Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000438459
Ethics application status
Approved
Date submitted
5/05/2025
Date registered
12/05/2025
Date last updated
22/06/2025
Date data sharing statement initially provided
12/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Centralized Platform study for Functional High Risk Multiple Myeloma: Domain 1
Scientific title
A Centralized Platform study for Functional High Risk Multiple Myeloma: Domain 1 - Talquetamab and Teclistamab
Secondary ID [1] 314362 0
AMaRC 24-01-01
Universal Trial Number (UTN)
Trial acronym
ZEPFHR-MM Domain 1
Linked study record
Refer to ZEPFHR-MM Master Protocol record in ANZCTR (ACTRN12625000429459)

Health condition
Health condition(s) or problem(s) studied:
Multiple myeloma 337357 0
Myeloma 337356 0
Relapsed refractory myeloma 337358 0
Condition category
Condition code
Cancer 333740 333740 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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
Intervention code [1] 330978 0
Treatment: Drugs
Comparator / control treatment
Single group/arm i.e no control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341330 0
To demonstrate the efficacy of the combination of teclistamab and talquetamab in FHR MM patients
Timepoint [1] 341330 0
Achievement of a partial response (PR) or better at any time within the first four cycles of treatment, assessed at Cycle 5 unless participant comes off treatment earlier.
Secondary outcome [1] 447154 0
To obtain an estimate of Event-free survival (PFS)
Timepoint [1] 447154 0
Measured from the date of first dose of study drug until the earliest of the dates of withdrawal for any reason, PD or death, whichever comes first. This will be assessed from Cycle 1 Day 1, at day 1 of each subsequent cycle until the disease progression. There is no time limit.
Secondary outcome [2] 447156 0
To obtain an estimate of the Time to progression (TTP)
Timepoint [2] 447156 0
Measured from the date of first dose of study drug until the date that progressive disease is first observed. This will be assessed from Cycle 1 Day 1, at day 1 of each subsequent cycle until the disease progression. There is no time limit.
Secondary outcome [3] 447155 0
To obtain an estimate of the Duration of response (DoR)
Timepoint [3] 447155 0
Measured from the date that a response of PR or better is first achieved until the date that response is lost. Response will be measured day 1 of each cycle until the disease progression. There is no time limit.
Secondary outcome [4] 447153 0
To obtain an estimate of Progression-free survival (PFS)
Timepoint [4] 447153 0
Measured from the date of first dose of study drug until the earlier of the date that progressive disease (PD) is first observed or the date of death. Response will be measured day 1 of each cycle until the disease progression. There is no time limit.

Eligibility
Key inclusion criteria
- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
As this is a platform trial, there will be multiple domains within this platform study. Each domain will be independent of each other. Domains will be activated based on site preference/clinical need for local population. Site investigators will choose which domain/intervention a participant will enrol into based on investigator’s assessment.
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/05/2025
Actual
11/06/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 27889 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [2] 27887 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 27888 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 27891 0
Concord Repatriation Hospital - Concord
Recruitment hospital [5] 27885 0
The Alfred - Melbourne
Recruitment hospital [6] 27890 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [7] 27892 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 27886 0
Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 44084 0
2170 - Liverpool
Recruitment postcode(s) [2] 44082 0
3128 - Box Hill
Recruitment postcode(s) [3] 44087 0
2139 - Concord
Recruitment postcode(s) [4] 44083 0
2050 - Camperdown
Recruitment postcode(s) [5] 44081 0
3004 - Melbourne
Recruitment postcode(s) [6] 44085 0
3220 - Geelong
Recruitment postcode(s) [7] 44086 0
2298 - Waratah
Recruitment postcode(s) [8] 44088 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 318883 0
Government body
Name [1] 318883 0
Australian Government Department of Health and Aged Care: Medical Research Future Fund
Country [1] 318883 0
Australia
Funding source category [2] 318887 0
Other Collaborative groups
Name [2] 318887 0
Australasian Myeloma Research Consortium
Country [2] 318887 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Myeloma Research Consortium
Address
Country
Australia
Secondary sponsor category [1] 321349 0
None
Name [1] 321349 0
Address [1] 321349 0
Country [1] 321349 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317496 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 317496 0
Ethics committee country [1] 317496 0
Australia
Date submitted for ethics approval [1] 317496 0
23/09/2024
Approval date [1] 317496 0
27/11/2024
Ethics approval number [1] 317496 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 141242 0
Prof Andrew Spencer
Address 141242 0
Alfred Health, 55 Commercial Road, MELBOURNE VIC 3004
Country 141242 0
Australia
Phone 141242 0
+61 3 9076 3393
Fax 141242 0
Email 141242 0
[email protected]
Contact person for public queries
Name 141243 0
Khoa Le
Address 141243 0
Level 2, South Block, Alfred Health, 55 Commerical Road, Melbourne VIC 3004
Country 141243 0
Australia
Phone 141243 0
+61 3 9076 7851
Fax 141243 0
Email 141243 0
[email protected]
Contact person for scientific queries
Name 141244 0
Prof. Andrew Spencer
Address 141244 0
Level 2, South Block, Alfred Health, 55 Commerical Road, Melbourne VIC 3004
Country 141244 0
Australia
Phone 141244 0
+61 3 9076 7851
Fax 141244 0
Email 141244 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.