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OncoMatch/Clinical Trials/NCT05082259

ASTEROID: A Trial of ASTX660 in Combination With Pembrolizumab

Is NCT05082259 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments including ASTX660 and Pembrolizumab for advanced cancer.

Phase 1RecruitingInstitute of Cancer Research, United KingdomNCT05082259Data as of May 2026

Treatment: ASTX660 · PembrolizumabThis 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.

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Extracted eligibility criteria

Cancer type

Tumor Agnostic

Cervical Cancer

Triple-Negative Breast Cancer

Breast Carcinoma

Biomarker criteria

Required: IDH1 wild-type

IDH wild type diffuse astrocytic glioma with microvascular proliferation, OR necrosis, OR one or more of the following molecular features of GBM

Required: TERT promoter mutation

TERT promoter mutation

Required: EGFR amplification

EGFR gene amplification

Performance status

WHO 0–1

Prior therapy

Must have received: immune checkpoint inhibitor (anti-PD-1, anti-PD-L1)

refractory to immune checkpoint inhibitors and for which no conventional therapy exists or is declined by the patient

Must have received: CDK4/6 inhibitor

Patients with histologically or cytologically confirmed ER positive HER2 negative breast cancer who have progressed on CDK4/6 inhibitor therapy

Cannot have received: IAP antagonist (Smac mimetic)

Patients with prior exposure to an IAP antagonist (Smac mimetic) will be excluded from this study

Lab requirements

Blood counts

Haemoglobin (Hb) ≥ 9.0 g/dL; Absolute neutrophil count ≥ 1.5 x 10^9/L; Lymphocyte count >0.5 x 10^9/L; Platelet count ≥ 100 x 10^9/L

Kidney function

Calculated creatinine clearance ≥ 50 mL/min (uncorrected value) OR Creatinine < 1.5 x upper limit of normal (ULN)

Liver function

Total Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 2.5 x (ULN) unless raised due to known metastatic liver disease in which case ≤ 5 x ULN is permissible; Aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to known metastatic liver disease in which case ≤ 5 x ULN is permissible

Cardiac function

Mean resting corrected QT interval (QTcF) > 470 msec obtained from an electrocardiogram (ECG). Known congenital QT syndrome or history of torsades de pointes. Left ventricular ejection fraction of <50% on echocardiogram. Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete left bundle branch block, third degree heart block. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association [NYHA Grade 2 or above], severe valvular disease, uncontrolled hypertension despite optimal therapy.

Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) prior to the patient's first dose of IMP.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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