MoST-LLy Cancer Clinical Trials

30 March 2022

New blood cancer and genomic trials have just opened at the RAH in collaboration with SA Pathology. The trials provide fresh hope for those who are out of standard-of-care options.

MoST-LLy is a sub-study specifically for Leukemia and Lymphoma and uses the experience and platform of MoST - Molecular Screening and Therapeutics already running in SA with Prof Michael Brown (RAH) and GMP. MoST-LLy was established by Professor Steven Lane, from the Royal Brisbane Clinical Unit, with Professor Hamish Scott as Scientific lead and SA Pathology’s GMP team as the lead molecular testing site and seeks to help those living with rare or advanced blood cancers. 

This trial could be vital in securing new targeted treatments for patients suffering from high-grade lymphoma and myeloid malignancies and has been generously funded by The Leukaemia Foundation, Tour de Cure  as well as The Medical Research Future Fund (MRFF).

Adelaide joins Brisbane in the trial, and Perth and Hobart are expected to come on board at a later date. Leading this trial is Associate Professor David Ross, Dr Danielle Blunt, Research Associate Diana Iarossi, and Professor Hamish Scott.

 Typically, trials of this nature are delivered in cities such as Melbourne and Sydney, but this time is different says Assoc Prof David Ross, “they deliberately chose Perth and Hobart because they are somewhat underrepresented in other clinical trials, so I guess it was partly about equity…to give people more opportunity.” 

SA Pathology is the first laboratory completing the molecular genomic screening for the MoST-LLy trial, and patient samples from all sites but Perth will also come through SA Pathology. This will help to even out the Laboratory demand, and build further expertise, specifically in haematological tumours, in South Australia.  

The participants chosen for the trials will have been receiving other therapies and will have come to the stage where they no longer have a standard therapy choice available.

Assoc Prof Ross says when this happens, the clinician can refer the patient for MoST-LLy. “The initial referral involves providing a sample of the tumour, which may be a biopsy piece of lymphoma or may simply be blood or marrow in case of the other myeloid malignancies. This, together with a treatment history and background history will be collected for the overall database”. 

The first study is for high-grade lymphoma, predominantly of Relapsed or Refractory Diffuse Large B Cell Lymphoma. “This is an aggressive tumour that can be cured with intensive chemotherapy in the earlier stage of the disease, but with more advanced disease the cure rate drops substantially.” Patients can also relapse within one or two years and after subsequent lines of treatment the duration of response commonly shortens, and the options diminish.

This study is what’s known as a basket trial, the treatment used is already decided and the patient will be placed on it to figure out which patients will respond best in the future.

Assoc Prof Ross says the treatment will be “a combination of Acalabrutinib, a Bruton Tyrosine Kinase Inhibitor, which has been used in other types of lymphoma, together with an immune targeted drug, Durvalumab… 

All patients will be treated but then they’ll look later at genomic factors to help find out who is going to have a better response so that in the future better-targeted studies can be designed.”

Two patients have consented so far for screening (as of March 18), and if they appear suitable, they can then consent to the clinical trial.

The second study, expected to open in 1-2 months, uses PARP inhibitors to treat myeloid malignancies. Pamiparib is a path inhibitor that is involved in DNA repair pathways.

“The idea is that tumours are deficient in DNA repair, which could either be because of something the person is born with, or it could be specific to the tumour.” 

PARP inhibitors are used in the treatment of ovarian cancer, but applying them to haematological malignancies, “is still relatively novel”.

Patients will only be enrolled in the study if they have a genomic signature that is thought to be vulnerable to PARP inhibition. Assoc Prof Ross and Trial Coordinator Diana Iarossi, expect this will be no more than one in every ten patients screened.  

The team are looking for approximately 16 participants for each sub study, but many more will need to be screened in the search.

SA Pathology is proud to be a part of this ground-breaking research in paving the way for people experiencing blood cancer to recover. Thank you to David, Danielle, Diana and Hamish and the Genomics and Molecular Pathology Laboratory team.

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