RecruitingPhase 1NCT05082259

ASTEROID: A Trial of ASTX660 in Combination With Pembrolizumab

ASTEROID:A Phase I Trial of ASTX660 in Combination With Pembrolizumab in Patients With Solid Tumours: Utilizing Triple IAP Blockade as a Strategy to Maximize Immunogenic Cell Death and the Generation of an Efficient Adaptive Immune Response

Sponsor

Institute of Cancer Research, United Kingdom

Enrollment

61 participants

Start Date

Mar 2, 2022

Study Type

INTERVENTIONAL

Conditions

Cervical Cancer Advanced Cancer

Summary

This is a multi-centre Phase I dose finding and proof-of-concept study of the combination of ASTX660 together with Pembrolizumab with expansion cohorts testing preliminary efficacy in immune-refractory cancers, triple negative breast cancer (TNBC), cervical cancer, and glioblastoma. In contrast to the existing studies combining first-generation cIAP1/2 selective Smac mimetics with immune check point inhibitors, the ASTEROID Phase I clinical trial will be the first trial utilising triple cIAP1/2 and XIAP blockade by ASTX660 as a strategy to maximise immunogenic cell death and the generation of an efficient adaptive immune response. ASTX660 is not simply being used to repeat the data already being acquired with other first generation Smac mimetics. In contrast, we will investigate more in depth the mechanisms by which ASTX660 elicits its therapeutic effects both on tumour and on the host immune system. This will be critical to determine the best strategy to pursue in future later stage tumour specific trials of IAP antagonists in combination with immunotherapy, and to ensure appropriate molecular stratification biomarkers for the greatest benefit to patients.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial (ASTEROID) is testing a drug called ASTX660 (which blocks proteins that prevent cancer cells from dying) in combination with pembrolizumab (an immunotherapy) in people with various advanced solid tumors that have not responded to standard treatments. **You may be eligible if...** - You have confirmed advanced solid tumors that are refractory (no longer responding) to standard treatment, or for which no standard treatment exists - Depending on the study part: this includes melanoma, kidney cancer, lung cancer, head and neck cancer, cervical cancer, triple-negative breast cancer, or other solid tumors - For glioblastoma (brain cancer): must have recurrent IDH wild-type glioblastoma - Your general health and organ function must be adequate **You may NOT be eligible if...** - You have not yet tried standard treatments for your cancer type - You are pregnant or breastfeeding - You have active severe autoimmune disease or recent major illness - Your cancer has not been confirmed by pathology (biopsy) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGASTX660

ASTX660 will be supplied as capsules. Each hydroxylpropyl methylcellulose (HPMC) capsule contains either 30 mg or 90 mg of ASTX600 free-base equivalents, suitable for oral administration. Bottles are labelled with the capsule strength (ie, 30 mg or 90 mg) and are further distinguished by different-colored labels. Each bottle contains 14 capsules and an oxygen-absorber (not to be consumed).

DRUGPembrolizumab

Pembrolizumab Solution for Infusion 100 mg/vial is a liquid drug product supplied as a clear to opalescent solution, essentially free of visible particles, in Type I glass vials and manufactured using the fully formulated drug substance with L-histidine as buffering agent, polysorbate 80 as surfactant, and sucrose as stabilizer/tonicity modifier. Pembrolizumab Solution for Infusion can be further diluted with normal saline or 5% dextrose in the concentration range of 1 to 10 mg/mL in IV containers made of polyvinyl chloride (PVC) or non-PVC material.