MoST therapeutic studies

MoST Core Studies (C1)

MoST 4 substudy 9: Vismodegib

Title: Single arm, open label, signal seeking, phase IIa trial of the activity of vismodegib in patients with tumours harbouring PTCH1 or SMO mutations

The aim of this MoST substudy is to assess the clinical value of Hedgehog pathway inhibition in patients with advanced cancers harbouring mutations in PTCH1 or SMO.

Eligible Population: Participants will be enrolled in the MoST program for molecular screening and eligible for this study if a germline or somatic mutation in PTCH1 or SMO is identified in their tumour. Those with tumours harbouring SUFU mutations or particular mutations in SMO known to affect vismodegib binding (ie. SMO G497W, SMO D473Y) are excluded.

Substudy status: recruiting

ANZCTR registration number: ACTRN12618000281291

ANZCTR registration details

MoST 5 substudy 10: Eribulin

Title: Single arm, open label, signal seeking, phase IIa trial of the activity of eribulin in patients with advanced CD31 positive angiosarcoma and selected CD31 positive sarcomas.

The aim of this MoST substudy is to assess the activity of eribulin in a population of patients with metastatic or unresectable angiosarcoma and other selected CD31 positive sarcomas.

Eligible Population: Patients with metastatic or unresectable CD31+ angiosarcoma or other selected CD31+ sarcomas including malignant and progressive epithelioid hemangioendothelioma (2:1 in favour of angiosarcoma or other selected CD31+ sarcomas, including epithelioid hemangio-endothelioma (EHE)))

Substudy status: closed to recruitment

ANZCTR registration number: ACTRN12618000357257

ANZCTR registration details

MoST 6 substudies 14-15: Larotrectinib

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.

Substudy status: recruiting

ANZCTR registration number: ACTRN12619001147178

ANZCTR registration details

MoST 7 substudies 16-18: Tremelimumab

Title:  Single arm, open label, signal seeking, phase II trial of Tremelimumab in patients with tumours with advanced rare or neglected cancers

The aim of this MoST substudy is to assess the clinical activity of of tremelimumab in a population of patients with advanced cancer and rare or neglected disease grouped post-hoc on the basis of tumour mutational burden (TMB) score/status.

Eligible Population: Participants will be enrolled in the MoST program for molecular screening and be eligible for this substudy on the basis of high or medium ordinally ranked tumour mutational burden (TMB) score/status.

Substudy status: recruiting

ANZCTR registration number: ACTRN12620000918921

ANZCTR registration details

MoST 8 substudies 19-20: TDM1 (Kadcyla)

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.

Solid tumours:

Group 1: activating HER2 mutation; Group 2: HER2 amplification in the absence of a HER2 mutation – Breast and gastric cancers will not be eligible for group 2.

Newly diagnosed metastatic, non-squamous NSC Lung Cancer (ASPiRATION study):

Group 3: activating HER2 mutation; Group 4: HER2 amplification in the absence of a HER2 mutation

Substudy status: recruiting

ANZCTR registration number: ACTRN12619001265167

ANZCTR registration details

MoST 9 substudies 21-22: Tucatinib plus Trastuzumab

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: Adult patients with tumours expressing HER2, if a somatic HER2 amplification or mutation is identified in their tumour, their primary cancer is not breast or gastric cancer (for the HER2 amplified group) and they have not received any previous HER2 directed therapy.

Substudy status: in start up

ANZCTR registration number: ACTRN12620000767909

ANZCTR registration details

MoST 10 substudies 23-24: Palbociclib and Avelumab

Title: Single arm, open label, signal seeking, phase II trial of the activity of Palbociclib in combination with Avelumab in patients with tumours with amplified D-type cyclins or CDK4/6 or inactivation of CDKN2A

The aim of these MoST substudies is to assess the clinical activity of combination of palbociclib and avelumab after initial priming with palbociclib in patients with advanced cancer with eligible mutations of the following:

  1. Gain-of function mutations in CDK4 and CCND1-3
  2. CDKN2A deletion or loss-of-function mutations

Eligible Population: Adults with tumours expressing amplified D-type cyclins or CDK4/6 or inactivation of CDKN2A. Group 1: Gain-of-function mutation in CDK4 and CCND1-3 OR Group 2: CDKN2A deletion or loss-of-function mutations

Substudy status: recruiting

ANZCTR registration number: ACTRN12620000568910

ANZCTR registration details

MoST 11 substudies 25-26: Tildrakizumab

Title: Single arm, open label signal seeking, phase II trial to study the clinical activity of Tildrakizumab in patients with advanced osteosarcoma and soft tissue sarcomas.

The aim of these MoST substudies is to assess the clinical activity of tildrakizumab in patients with advanced osteosarcomas or soft tissue sarcomas.

Eligible Population: Treatment-refractory advanced osteosarcoma and other sarcomas.

Substudy status: recruiting

ANZCTR registration number: ACTRN12620000984998

ANZCTR registration details

MoST 12 substudies 27-30: Vemurafenib and Cobimetinib

Title: Single arm, open label, phase II trial of vemurafenib and cobimetinib in patients with metastatic non-squamous non-small cell lung cancer and other tumours harbouring BRAF V600 mutations detected by comprehensive genomic profiling.

The aim of this ASPiRATION and MoST substudy is to assess the clinical activity of combination of vemurafenib and cobimetinib in patients with newly diagnosed metastatic non-squamous small cell lung cancer (NSCLC) or other tumours harbouring BRAF V600 mutations.

Eligible Population: Adult patients with pathologically confirmed metastatic non-squamous NSCLC or other advanced cancers harbouring a BRAF V600 mutation.

Substudy status: recruiting

ANZCTR registration number: ACTRN12620000984998

ANZCTR registration details

MoST 13 substudy 31: Entrectinib

Title: A single-arm, open-label, phase II trial of entrectinib in patients with advanced tumours harbouring NTRK fusions or ROS1 gene rearrangements detected by comprehensive genomic profiling.

The aim of this ASPiRATION and MoST substudy is to assess the clinical activity of entrectinib in adult patients with advanced cancers harbouring NTRK or ROS1 gene alterations.

Eligible Population: Adult patients with advanced cancers harbouring NTRK fusions or ROS1 gene rearrangements. NSCLC patients with ROS1 gene alterations must be FISH-negative, i.e. not eligible for reimbursed ROS1-targeted treatment.

Substudy status: recruiting

ANZCTR registration number: ACTRN12621000284864

ANZCTR registration details

MoST 14 substudy 32: Alectinib

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

ANZCTR registration number: ACTRN12621000312842

ANZCTR registration details

MoST 15 substudies 33-34: Durvalumab plus Acalabrutinib

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

ANZCTR registration number: ACTRN12621000507886

ANZCTR registration details

MoST 16 substudy 37: Pamiparib

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: in development

ANZCTR registration number: ACTRN12621001183875

ANZCTR registration details

MoST 17 substudies 38-39: Tepotinib

Title: A single arm, open label, signal-seeking, phase II trial of tepotinib in patients with advanced non-small cell lung cancer harbouring MET exon 14 skipping mutations detected by comprehensive genomic profiling.

The aim of this ASPiRATION and MoST substudy is to evaluate the activity of tepotinib in metastatic non-squamous NSCLC with METex14 mutations detected by CGP

Eligible Population: Adult patients with newly diagnosed metastatic non-squamous NSCLC with METex14 skipping mutation identified using CGP.

Substudy status: recruiting

ANZCTR registration number: ACTRN12621000811808

ANZCTR registration details

MoST 18 substudy 40: Durvalumab plus Chemotherapy

Title: A single-arm, open-label, signal-seeking, phase II trial of durvalumab and chemotherapy in patients with extra-pulmonary small cell carcinoma 

The aim of this  MoST substudy is to assess the clinical activity of first line durvalumab and chemotherapy in patients with ES-EPSCCP

Eligible Population: Adult patients with treatment naïve ES-EPSCC enrolled on the MoST program are eligible for this study.

Substudy status: in start-up

ANZCTR registration number: ACTRN12621001225808

ANZCTR registration details

MoST 19 substudies 41 – 42: Sotorasib

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: in development

ANZCTR registration number: pending

MoST Companion Studies (C2)

MoST CIRCUIT - ipilimumab and nivolumab

The CIRCUIT trial participants will be invited to have tissue assessed for a molecular profile and provide:

  • Predictive biomarkers of response to combination checkpoint inhibitors in a cohort of patients with rare/neglected advanced solid tumours
  • Other opportunities for treatment for patients who progress on immunotherapy via the program of MoST therapeutic substudies.

Title: Combination Immunotherapy in Rare Cancers Under InvesTigation: ipilimumab and nivolumab combination therapy in patients with selected immunotherapy sensitive advanced rare cancers

The aim of this MoST companion study is to assess the clinical efficacy of of ipilimumab/nivolumab in rare cancer histotypes.

Eligible Population: Histologically confirmed Neuroendocrine cancers: Atypical bronchial carcinoid, neuroendocrine carcinoma and Grade 3 NETs independent of primary site (SCLC excluded); Biliary Tract Cancers: Intrahepatic cholangiocarcinoma, gallbladder carcinoma; Gynaecological malignancies: Ovarian clear cell carcinoma, uterine clear cell carcinoma, uterine/ovarian carcinosarcoma, uterine leiomyosarcoma, vaginal/vulva squamous cell carcinoma; Mismatch repair protein deficient (MSI-H) cancers (excluding colorectal carcinoma).

Substudy status: recruiting

Registration number: NCT04969887

ClinicalTrials.gov registration details

MoST CRESTONE - Seribantumab

MoST CRESTONE is the subset of patients enrolled to the global multicenter open-label phase II clinical trial in Australia.

Title: CRESTONE: A Phase 2 Study of Seribantumab in Adult Patients with Neuregulin-1 (NRG1) Fusion Positive Locally Advanced or Metastatic Solid Tumors

The aim of this MoST companion study is to assess the clinical efficacy seribantumab in patients with NRG1 fusion positive locally advanced or metastatic solid tumours.

Eligible Population:

  • Cohort 1: patients with centrally confirmed NRG1 gene fusions who are ERBB/HER2/HER3 treatment-naïve AND harbor NRG1 gene fusions with an EGF-like domain intact
  • Cohort 2: patients with NRG1 fusions with an EGF-like domain intact, who have progressed after prior standard therapy, including prior ERBB/HER2/HER3 directed treatment
  • Cohort 3: patients with NRG1 fusions without an EGF-like domain including but not limited to NRG1-PMEPA1, NRG1-STMN2, PCM1-NRG1 and INTS9-NRG1; patients with NRG1 fusions and other molecular aberrations lacking standard treatment options; AND patients unable to provide sufficient tissue for central confirmation of NRG1 gene fusion status.

Substudy status: in development

Registration number: pending

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