ASTEROID: A Trial of ASTX660 in Combination With Pembrolizumab (NCT05082259) | Clinical Trial Compass
Active — Not RecruitingPhase 1
ASTEROID: A Trial of ASTX660 in Combination With Pembrolizumab
United Kingdom61 participantsStarted 2022-03-02
Plain-language 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.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. PART A: Patients with histologically or cytologically confirmed malignant advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient.
. Has received at least 2 doses of an approved anti-PD-1/PD-L1 mAb.
. Has demonstrated disease progression after anti-PD-1/PD-L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in c below).
. Progressive disease has been documented within 24 weeks from commencing anti-PD-1/PD-L1 and no later than 12 weeks from the last dose of anti-PD-1/PD-L1 mAb.
. Parts A, B1, and B2: Measurable disease as assessed by imRECIST. Parts B3 and B5 : Measurable disease as assessed by imRECIST OR Evaluable disease as assessed by whole body MRI.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Determination of MTD and RP2D
Timeframe: 12 months
2
Safety and tolerability
Timeframe: 12 months
3
Preliminary anti-tumour activity evaluation (in Part B)
Timeframe: 24 months
Trial details
NCT IDNCT05082259
SponsorInstitute of Cancer Research, United Kingdom
. Patients in the ER positive HER2 negative cohort (cohort B5 ) must not have had more than two prior systemic lines of chemotherapy in the metastatic setting. There is no limitation on number of prior lines of hormonal or targeted therapies.
. All patients with advanced solid tumours enrolled onto Part A must be willing and able to have fresh paired tissue biopsies for biomarker analysis.
. Life expectancy of at least 12 weeks.
Exclusion criteria
. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy including Pembrolizumab or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and four weeks for investigational medicinal products, except for hormonal therapy with luteinizing hormone-releasing hormone (LHRH) analogues for medical castration in patients with castrate resistant prostate cancer or ovarian suppression in pre- or peri-menopausal women with endocrine-driven breast cancer, which are permitted, and bisphosphonates or RANK ligand antagonists that are permitted for the management of bone metastases.
. Current malignancies of other types, with the exception of adequately treated cone biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years or more and are deemed at negligible risk for recurrence, are eligible for the trial.
. Ongoing Grade 2 or greater toxicities from pre-existing conditions or previous treatments. Exceptions to this are alopecia and ongoing anticoagulation therapy due to prior thromboembolic episodes.
. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible. NB. Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] and not to donate sperm during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
. For cohorts A, B1, B2, B3 and B5 only - Known untreated or active central nervous system (CNS) metastases (progressing or requiring corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
. For Cohort B4 only (no longer recruiting):
. Major surgery within four weeks of the first dose of study treatment.