A Phase II Exploratory Study of Durvalumab (MEDI4736) in HIV-1 Patients With Advanced Solid Tumors.
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- HIV
- Sponsor
- Spanish Lung Cancer Group
- Enrollment
- 20
- Locations
- 8
- Primary Endpoint
- Best Response During the Treatment Period
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent
- •Age \> 18 years at time of study entry.
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Life expectancy of \> 16 weeks
- •Adequate normal organ and marrow function.
- •Female subjects must either be of non-reproductive potential
- •Subject is willing and able to comply with the protocol
- •Subjects with histologically or cytologically advanced/metatasic-documented lung cancer, head and neck cancer, cervical cancer, melanoma, anal cancer, pancreatic cancer, gastrio-esophageal cancer, triple negative breast cancer, bladder or renal cancer, Cholangiocarcinoma, Kaposi sarcoma, lymphomas, ovarian cancer or Merkel cell carcinoma or any other tumor type in which anti PD-L1 antibodies have desmonstrated antitumoral activity, refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists or who refuse the standard treatment.
- •Subjects may be included irrespectively of number of previous lines of treatment for advanced disease.
- •Prior palliative radiotherapy must have been completed at least 2 weeks prior to start the study treatment (subjects may receive localized palliative radiotherapy while receiving study drug).
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study. Previous enrollment in the present study.
- •Participation in another clinical study within last 4 weeks.
- •Other untreated coexisting HIV related malignancies.
- •Any previous treatment with a PD1, PD-L1 or PD-L2 inhibitor, including durvalumab.
- •Receipt of the last dose of anti-cancer therapy within 28 days prior to the first dose of study drug.
- •Mean QT interval corrected for heart rate (QTc) ≥470 ms
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab,
- •Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy.
- •Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade
- •Active or prior documented autoimmune disease within the past 2 years
Arms & Interventions
Arm 1
Durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients
Intervention: Durvalumab
Outcomes
Primary Outcomes
Best Response During the Treatment Period
Time Frame: From the first dose until last follow up, assessed up to 24 month
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).
Secondary Outcomes
- Duration of Response Global(From the time from first response evaluation to progression or death, assessed up to 24 months.)
- Progression Free Survival (PFS)(From the date of randomization until end of follow up, assessed up to 24 months.)
- Duration of Response- Dolutegravir/ no Dolutegravir(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(From the date of the first response until progression or death, assessed up to 24 months)
- OS Analysis by PD-L1(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 Dolutegravir(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 Integrase Inhibitors(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(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 Dolutegravir(From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.)
- PFS Analysis by Integrase Inhibitors(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.)