Title: A single arm, open label, phase II trial of alectinib in patients with advanced tumours harbouring ALK gene alterations detected by comprehensive genomic profiling

The aim of this ASPiRATION and MoST substudy is to assess the clinical activity of of alectinib in adult patients with advanced cancers harbouring an ALK gene alteration.

Eligible Population: 

Adult patients with advanced cancers harbouring ALK gene alterations identified using CGP. NSCLC patients with ALK gene alterations must be FISH-negative, i.e. not eligible for reimbursed ALK-targeted treatment.

Substudy status: Recruiting

Registration number: ACTRN12621000312842

Title: Single arm, open label, signal seeking, phase II trial of pamiparib in patients with relapsed/ refractory myeloid haematological malignancy with aberrant germline or somatic DNA repair pathway function

The aim of this MoST-LLy substudy is to assess the clinical activity of pamiparib in patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) with germline or somatic DNA repair pathway mutation (e.g. BRCA1/2), and/or BRCA mutational signature.

Eligible Population: 

Adult patients with acute myeloid leukaemia or myelodysplastic syndrome who have no standard of care options or have failed these options and have enrolled in the MoST program and found to have germline or somatic DNA repair pathway mutation (e.g. BRCA1/2), and/or BRCA mutational signature.

Substudy status: Recruiting

Registration number: ACTRN12621001183875

Title: Single arm, open label, signal seeking, phase IIa trial of the activity of Trastuzumab emtansine (T-DM1) in patients with tumours harbouring HER2 amplifications or mutations

The aim of these MoST substudies is to assess the clinical value of HER2 inhibition using T-DM1 in advanced cancer patients with tumours with (i) HER2 mutations and (ii) HER2 amplification.

Eligible Population: 

Participants will be enrolled in the MoST program for molecular screening and eligible for this study if their tumour demonstrates an activating HER2 mutation or HER2 amplification.

• Group 1 (CLOSED): activating HER2 mutation;
• Group 2 (CLOSED): HER2 amplification in the absence of a HER2 mutation - Breast and gastric cancers will not be eligible for group 2;
• Group 3-4: Metastatic, non-squamous NSCLC with activating HER2 mutation - 2nd and subsequent line only

Substudy status: Recruiting

Registration number: ACTRN12619001265167

Title: Single arm, open label, signal seeking, phase II trial of the activity of tucatinib plus trastuzumab in patients with tumours harbouring HER2 amplifications or mutations

The aim of these MoST substudies is to assess the clinical activity of tucatinib in combination with trastuzumab in a population of patients with advanced tumours harbouring HER2 amplification or mutations.

Eligible Population: 

• Advanced and/or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer.
• HER2 amplification (in the absence of a HER2 mutation).
• (CLOSED) Mutations (with or without concomitant amplification).
• Primary tumour histology is not HER2 amplified breast adenocarcinoma or gastric adenocarcinoma.
• They have not received any previous HER2 directed therapy.

Substudy status: Recruiting

Registration number: ACTRN12620000767909

Title: Single arm, open label, signal-seeking phase II study of Sotorasib (AMG-510) in patients with solid tumours harbouring KRAS G12C mutation

The aim of this MoST substudy is to assess the clinical activity of Sotorasib in adult patients with advanced cancers (excluding NSCLC and colorectal cancers) harbouring KRAS G12C mutations.

Eligible Population: 

Adult patients with treatment-refractory solid tumours (except non-small-cell lung and colorectal cancers) harbouring KRAS G12C mutation as determined by next generation sequencing panel.

Substudy status: Recruiting

Registration number: ACTRN12621001690842

Title: A single arm, open label, signal seeking, phase II trial of the activity of Durvalumab in combination with Acalabrutinib in patients with high-grade B cell lymphoma

The aim of this MoST-LLy substudy is to assess the clinical activity of durvalumab and acalabrutinib in patients with high grade B cell lymphoma.

Eligible Population: 

Adult patients with pathologically confirmed high grade B cell lymphoma enrolled in the MoST program for molecular screening are eligible for this study.

Substudy status: Recruiting

Registration number: ACTRN12621000507886

Title: Single arm, open label, signal seeking, phase IIa trial of the activity of larotrectinib in patients with advanced NTRK1-3 positive tumours

The aim of this MoST substudy is to assess the clinical activity of larotrectinib in a population of patients with advanced tumours harbouring NTRK1-3 rearrangments in (i) primary central nervous system (CNS) tumours and (ii) non-CNS cancers.

Eligible Population: 

Participants will be enrolled in the MoST program for molecular screening and be eligible for this substudy if a somatic NTRK1-3 rearrangment is identified in their tumour. 

• Cohort 1: Primary CNS cancer.
• Cohort 2 (CLOSED): Non-CNS cancer.

Substudy status: Recruiting

Registration number: ACTRN12619001147178