At a glance
ClinicalIndex Comparison Record- ✓Histologically or cytologically confirmed advanced solid tumors (Part A: treatment-refractory or no conventional therapy exists/declined)
- ✓Cervical cancer, treatment-refractory or no conventional therapy (Part B2)
- ✓Triple negative breast cancer, treatment-refractory or no conventional therapy (Part B3)
- ✓ICI-refractory solid tumors including melanoma, RCC, NSCLC, HNSCC (Part B1)
- ✕Radiotherapy (except palliative), endocrine therapy, immunotherapy including Pembrolizumab, or chemotherapy within 4 weeks (6 weeks for nitrosoureas/Mitomycin-C)
- ✕Current malignancies other than cervical in situ carcinoma or skin carcinoma
- ✕Ongoing Grade 2 or greater toxicities from previous treatments (except alopecia and anticoagulation)
- ✕Ability to become pregnant or currently pregnant/lactating without contraception agreement
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
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
In Brief
A Phase 1 clinical trial evaluating ASTX660 and Pembrolizumab for Advanced Cancer and 2 related conditions. Active but no longer recruiting, targeting 61 participants across 3 sites.
Detailed 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.
Study Details
Timeline
Interventions
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).
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.