MoST addendum 2 and substudy 2 – 5: Single arm, open label, signal seeking, phase IIa trial of the activity of Durvalumab (MEDI4736) in combination with Tremelimumab in patients with advanced rare or neglected cancers.

Trial Summary:

Blockade of immune checkpoint inhibitors, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) can amplify T-cell responses against tumors and lead to control or elimination of tumours. Durvalumab is a human monoclonal antibody (mAb) that inhibits PD-L1 and Tremelimumab is mAb blocking CTLA-4, two immunomodulatory therapies.

We hypothesise that patients with rare or neglected cancers may benefit from the combination of durvalumab and tremelimumab. We further hypothesise that tumour-infiltration with immune cells, expression of PD-L1, or tumour mutational burden may predict benefit to treatment.

The aim of substudies 2-5 is to assess the clinical activity of durvalumab and tremelimumab in a population of patients with advanced cancer and rare or neglected disease grouped post-hoc on the basis of tumour expression of PD-L1 and tumour infiltrating lymphocytes (TILs) and Tumour Mutational Burden (TMB).

To be eligible for this substudy, participants must continue to meet all of the inclusion criteria and none of the exclusion criteria specified in the MoST framework protocol (sections 5.3-5.8) and, in addition, meet all the inclusion criteria and none of the exclusion criteria at the time of registration. 

Supported By:

OHMR, CGMP, Astra Zeneca


Patients with pathologically confirmed advanced or metastatic solid cancer of any histologic type with a focus on rare or neglected cancers. Patients will be enrolled in the MoST program for molecular screening and eligible for this study if no actionable mutation is found through genomic panel sequencing.

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David Thomas