Preliminary Assessment of Safety and Tolerability of Dostarlimab in Combination Antiretroviral Therapy (cART) Refractory HIV Associated Kaposi Sarcoma

NCT05646082 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 21IC6896
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Refractory HIV Associated Kaposi Sarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (safety and tolerability)

  The safety and tolerability of pembrolizumab will be assessed by recording the incidence of adverse events (AEs) using National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTC criteria v.5.0

  90 days after treatment

Secondary Outcomes (1)

• Improvement of progression-free survival rate (efficacy)

  week 13, 31 and end of treatment

Study Arms (1)

Open Label

EXPERIMENTAL

Drug: Dostarlimab in Combination Antiretroviral Therapy

Interventions

Dostarlimab in Combination Antiretroviral Therapy DRUG

Patients will receive dostarlimab at the fixed dose of 500 mg dose Q3W for the first 4 doses followed by a fixed 1000 mg dose Q6W until week 48 of treatment.

Open Label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Note: modifications of cART during screening are allowed provided patients meet all other eligibility criteria and are on effective new regimen for at least 2 weeks.
• 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:
• Absolute neutrophil count \>1.500/mcL, Platelet count \>100.000/mcL, Haemoglobin \>90 g/L, Total bilirubin ≤1.5x upper limit of normal (ULN) or ≤2xULN for patients with Gilbert's syndrome or on HIV protease inhibitors, Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5x ULN (up to 5x ULN if liver metastases are present), Serum creatinine ≤2.5x ULN or creatinine clearance (CrCl) \>60 ml/min in subjects with serum creatinine ≤1.5x ULN. Calculation of CrCl should follow institutional standards.
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Female participants must have a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agree use a highly effective method of contraception from screening through 120 days after the last dose of study treatment or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
• ≥45 years of age and has not had menses for \>1 year
• Patients who have been amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
• Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate birth control method throughout the study, starting with the screening visit through 120 days after the last dose of study treatment. See Section 5.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

You may not qualify if:

• 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.
• Note: Patients with previous history of IRIS that has fully resolved at the time of screening are eligible.
• Known history of active uncontrolled hepatitis C virus (HCV) infection, defined as detectable plasma HCV RNA.
• Note: patients with positive HCV serology but negative HCV RNA or those successfully treated for HCV are eligible.
• Known history of active uncontrolled hepatitis B virus (HBV) infection, defined as detectable plasma HBV DNA in absence of therapy.
• Note: patients with HBV serology indicating immunization (i.e. positive hepatitis B surface antibody, HBsAb and negative core antibody HBcAb), patients with fully resolved acute HBV infection and those with chronic HBV infection adequately treated with antiviral therapy are eligible.
• 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.
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan.
• Prior therapy with anti-PD-1/PD-L1 and/or anti-CTLA-4 therapy either alone or in combination with other agents.
• Receipt of live vaccines within 30 days before the first dose of trial treatment and while participating in the trial; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 flu, rabies, bacillus Calmette-Guerin (BCG), and typhoid vaccine.
• Known hypersensitivity to dostarlimab components or excipients.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Chelsea & Westminster Hospital

London, SW10 9NH, United Kingdom

Location

MeSH Terms

Interventions

dostarlimab; Antiretroviral Therapy, Highly Active

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre, open label, single arm study

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: December 12, 2022
• Study Start: May 26, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

GB (1)