Preliminary Assessment of Safety and Tolerability of Dostarlimab in Combination Antiretroviral Th… (NCT05646082) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Preliminary Assessment of Safety and Tolerability of Dostarlimab in Combination Antiretroviral Therapy (cART) Refractory HIV Associated Kaposi Sarcoma
United Kingdom15 participantsStarted 2023-05-26
Plain-language summary
This is a phase 1b, open label, single arm study evaluating the safety and tolerability of the drug dostarlimab in combination antiretroviral therapy (cART) refractory HIV-associated Kaposi Sarcoma (KS), a rare type of cancer usually seen in people with the HIV infection.
Dostarlimab is a type of immunotherapy, and is a monoclonal antibody that has been designed to inhibit the receptor programmed death-1 (PD-1). One of the two ligands for PD-1 has been shown to be upregulated in KS patients, the PDL-1 ligand. By preventing PDL-1 form binding to PD-1, dostarlimab increases the body's immune response to attack more cancer cells.
The safety profile of dostarlimab in this specific cancer has not been explored. The primary aim of this study is therefore to provide confirmatory evidence of safety of dostarlimab in KS patients and to preliminary evaluate its effects on HIV reservoirs and assess how it causes its anti-cancer effects through studying tumour tissue before and after treatment.
This study will be conducted in two parts and will recruit a total of up to 20 patients.
Upon completion of screening investigations inclusive of a fresh tumour biopsy within a 28-days window, patients will receive dostarlimab at the fixed dose of 500 mg dose every 3 weeks for the first 4 doses followed by a fixed 1000 mg dose every 6 weeks. Treatment will be continued until loss of clinical benefit, unacceptable toxicity, patients' withdrawal or completion of a total of 48 weeks of treatment. Part 1 will consist of 6 patients being dosed and observed for toxicity for 21 days following first dose. A trial steering committee will evaluate any treatment related adverse events (AEs) and dose-limiting toxicities (DLTs) reported before deciding on whether to continue onto part 2, where a further 14 patients may be enrolled.
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
. Histologically proven diagnosis of Kaposi Sarcoma.
. Available pretreatment biopsy, either fresh (optimal) or archival (acceptable).
. Established on cART for at least 3 months and no symptomatic or laboratory AE associated with cART \> grade 1 by CTCAE criteria v 5.0.
. Have an HIV VL\<200 cp/ml and CD4+ T-cell count \>100/mm3 at screening.
. Have disease that is measurable by modified AIDS Clinical Trial Group (ATCG) Kaposi sarcoma response criteria.
. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
. Be of ≥ 18 years of age
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
Incidence of treatment-emergent adverse events (safety and tolerability)
. Have adequate haematological and organ function, defined as follows:
Exclusion criteria
. Participant is simultaneously enrolled in any interventional clinical trial.
. Participant has received anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy or biologic therapy) including investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy. There should be no evidence of treatment-related adverse events \> grade 1 by CTCAE criteria.
. Major surgery within 3 weeks prior to initiating protocol therapy. Study participant must have recovered from any adverse events relating to surgery.
. Known active tuberculosis (TB) in the first 6 weeks of treatment.
. Known active Immune Reconstitution Inflammatory Syndrome (IRIS) related to opportunistic pathogens.
. Known history of active uncontrolled hepatitis C virus (HCV) infection, defined as detectable plasma HCV RNA.
. Known history of active uncontrolled hepatitis B virus (HBV) infection, defined as detectable plasma HBV DNA in absence of therapy.
. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.