INTRODUCTION
Analysis of real-world outcomes of Australian newly diagnosed multiple myeloma (NDMM) patients from the Myeloma and Related Disease Registry (MRDR) shows that 20-25% of all NDMM cases relapse within 12 months of starting first-line (1L) treatment. This patient cohort, also known as early progressors (EP), have poorer survival outcomes compared to myeloma patients who relapse later. We categorise this as functional high-risk multiple myeloma (FHR MM). These poorer outcomes are still evident when FHR MM is redefined as relapsing within 18 months of starting 1L treatment, as shown in a post-hoc analysis of the CASTOR trial. Patients who have functional high-risk disease currently do not have optimal treatments available via the Pharmaceutical Benefits Scheme.
The ZEPFHR-MM trial is a world-first multicentre phase II platform study exploring the use of different novel (new) therapies in treating functional high-risk multiple myeloma. Each new therapy/combination are assessed in separate but parallel arms, called 'domains'. Each domain is assessed for effectiveness, safety and includes patient-reported outcomes and correlative research to better understand the scientific nature of FHR MM.
ZEPFHR-MM DOMAIN 1
The first domain of ZEPFHR-MM involves the use teclistamab and talquetamab and is one of the first investigator-initiated trials using this combination. Teclistamab and talquetamab are both bi-specific T-cell engaging antibodies. A bi-specific antibody is a molecule that can bind simultaneously to two specific protein targets. Talquetamab targets a protein on myeloma cells called G protein–coupled receptor class C group 5 member D (GPRC5D). Teclistamab targets a protein on myeloma cells called B-cell maturation antigen (BCMA). By targeting GPRC5D and/or BCMA proteins, talquetamab and teclistamab draw myeloma cells to T-cell (A type of white blood cell) to activate the immune system to kill these myeloma cells.
STATUS
Actively recruiting
CURRENT ENROLMENT
19 Patients
Recruitment updated as of March 2026
TARGET ENROLMENT
20 patients
CORRELATIVE STUDIES
Blood, bone marrow and saliva samples will be collected as part of the trial to better the genomic, immunological, proteomic and transcriptomic factors around FHR MM and how teclistamab and talquetamab works around these factors.
TRIAL PRINCIPAL INVESTIGATORS
Professor Andrew Spencer, Dr Sueh-li Lim
TIME FRAME
2025 – 2027
PARTICIPANTS
Patients with diagnosed multiple myeloma who demonstrate disease progression within 18 months of commencing first-line (1L) and/or primary refractoriness to induction therapy.
SITE LOCATIONS
- Alfred Hospital, VIC
- Concord Repatriation General Hospital, NSW
- Peter MacCallum Cancer Centre, VIC
- University Hospital Geelong, VIC
- Box Hill Hospital, VIC
- Austin Health, VIC
- Princess Alexandra Hospital, QLD
- Royal Prince Alfred Hospital, NSW
- Royal Brisbane and Women's Hospital, QLD
- Sir Charles Gairdner Hospital, WA