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 range18 Years
SexALL
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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
✓. Have adequate haematological and organ function, defined as follows:
Exclusion criteria
✕. Participant is simultaneously enrolled in any interventional clinical trial.
✕
What they're measuring
1
Incidence of treatment-emergent adverse events (safety and tolerability)
. 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.