The proposal is a phase II clinical study designed to assess the feasibility of durvalumab (MEDI4736) in HIV-1-infected individuals with solid tumors. Additionally, to obtain data that lets understand the possible benefit of this treatment in cancer patients and HIV infection, exploring if activity of durvalumab (MEDI4736) could be higher in cancer that has been produced at least in part due to the chronic immunosupression. Simultaneously, it will allow us to investigate the effect of disrupting this immunoregulatory pathway might have in reversing cancer pathways and HIV-specific T-cell function during persistent chronic HIV infection in humans.
PD-1/ PD-L1 coinhibitory pathway plays a significant role in the regulation of the immune response in both chronic infectious diseases and cancer. Preclinical and animal data support the safety and promising activity of anti-PD-1 antibody in HIV-1 infection. Demonstrated anticancer activity and safety profile of durvalumab (MEDI4736) in cancer clinical trials. Unlikely drug interactions of durvalumab (MEDI4736) and antiretroviral treatments. The proposal is a phase II clinical study designed to assess the feasibility of durvalumab (MEDI4736) in HIV-1-infected individuals with solid tumors. Additionally, to obtain data that lets understand the possible benefit of this treatment in cancer patients and HIV infection, exploring if activity of durvalumab (MEDI4736) could be higher in cancer that has been produced at least in part due to the chronic immunosupression. Simultaneously, it will allow us to investigate the effect of disrupting this immunoregulatory pathway might have in reversing cancer pathways and HIV-specific T-cell function during persistent chronic HIV infection in humans. In this regard, our hypothesis is: HIV patients with cancer have a similar outcome in terms of tolerability when treated with durvalumab (MEDI4736) monotherapy at the recommended dose than non HIV infected patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Durvalumab monotherapy of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients until progression significant clinical deterioration, unacceptable toxicity, any criterion for withdrawal from the trial or trial drug is fulfilled
ICO-Badalona
Badalona, Barcelona, Spain
Consorci Sanitari de Terrassa
Terrassa, Barcelona, Spain
H. Clínic i Provincial de Barcelona
Barcelona, Spain
H. Universitario Quirón Dexeus
Barcelona, Spain
Hospital Puerta de Hierro
Madrid, Spain
H. La Paz
Madrid, Spain
Hospital Virgen del Rocío
Seville, Spain
Hospital La Fe
Valencia, Spain
Best Response During the Treatment Period
To explore the feasibility of durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg in solid tumors in HIV-1-infected patients The best overall response is a result of a combination of tumor responses in target and nontarget lesions according to Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: From the first dose until last follow up, assessed up to 24 month
Duration of Response Global
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis. Duration of response is the time from response (R) to progression/death (P/D).
Time frame: From the time from first response evaluation to progression or death, assessed up to 24 months.
Progression Free Survival (PFS)
Defined as the length of time from the date of diagnose to the date of the first documented progression of disease. "Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions".A patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
Time frame: From the date of randomization until end of follow up, assessed up to 24 months.
Duration of Response- Dolutegravir/ no Dolutegravir
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis. Duration of response is the time from response (R) to progression/death (P/D).
Time frame: From the date of first response until progression or death, assessed up to 24 months.
Duration of Response by Treatment With INSTIs or no INSTIs
Only patients with best response Stable disease, Partial Response or Complete response during the treatment period are included in the response analysis. Duration of response is the time from response to progression/death.
Time frame: From the date of the first response until progression or death, assessed up to 24 months
OS Analysis by PD-L1
Kaplan Meier method will be used to estimate the survival function. OS will be mesure at 24 months.
Time frame: OS is defined as the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
OS Analysis by Integrase Inhibitors
OS is defined as the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored at the last contact date up to 24 months.
Time frame: From the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
OS Analysis by Dolutegravir
OS is defined as the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
Time frame: From the time from the inclusion date to the death, due to any cause. A patient who does not dies, is censored up to 24 months
PFS Analysis by PD-L1
Progression Free Survival defined as the length of time from the date of diagnosis to the date of the first documented progression of disease
Time frame: PFS is defined as the time from the inclusion date to the progression or death, due to any cause, up to 24 months patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
PFS Analysis by Integrase Inhibitors
Defined as the length of time from the date of diagnosis to the date of the first documented progression of disease
Time frame: From the inclusion date to the progression or death, due to any cause, up to 24 months. patient who does not progresses neither dies, is censored at the last tumor evaluation where no progression is detected.
PFS Analysis by Dolutegravir
PFS is defined as the time from the inclusion date to the progression or death, due to any cause, date.
Time frame: From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.
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