Durvalumab in HIV-1 Patients With Solid Tumors

A Phase II Exploratory Study of Durvalumab (MEDI4736) in HIV-1 Patients With Advanced Solid Tumors.

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.

Study Overview

• Status: Completed
• Conditions: Cancer; HIV
• Intervention / Treatment: Drug: Durvalumab

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • H. Universitario Quirón Dexeus
  • Barcelona, Spain, 08036
    • H. Clínic i Provincial de Barcelona
  • Madrid, Spain, 28222
    • Hospital Puerta de Hierro
  • Madrid, Spain
    • H. La Paz
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocío
  • Valencia, Spain
    • Hospital La Fe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Ico-Badalona
    • Terrassa, Barcelona, Spain, 08220
      • Consorci Sanitari de Terrassa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent
2. Age > 18 years at time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) 0-2
4. Life expectancy of > 16 weeks
5. Adequate normal organ and marrow function.
6. Female subjects must either be of non-reproductive potential
7. Subject is willing and able to comply with the protocol
8. 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.
9. Subjects may be included irrespectively of number of previous lines of treatment for advanced disease.
10. 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).
11. Documented HIV-1 infection.
12. Undetectable viral load in the last analysis.
13. Subjects with brain metastases are eligible if they are asymptomatic, are treated or are neurological stable for at least 2 weeks without the use of steroids or on stable or decreasing dose of<10mb daily prednisone or equivalent.
14. Subjects must be following an antiretroviral therapy at the moment of the inclusion.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study. Previous enrollment in the present study.
2. Participation in another clinical study within last 4 weeks.
3. Other untreated coexisting HIV related malignancies.
4. Any previous treatment with a PD1, PD-L1 or PD-L2 inhibitor, including durvalumab.
5. Receipt of the last dose of anti-cancer therapy within 28 days prior to the first dose of study drug.
6. Mean QT interval corrected for heart rate (QTc) ≥470 ms
7. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab,
8. Any unresolved toxicity (CTCAE grade 2) from previous anti-cancer therapy.
9. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1.
10. Active or prior documented autoimmune disease within the past 2 years
11. Any syndrome that requires systemic corticosteroid/immunosuppressive medications
12. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
13. History of primary immunodeficiency.
14. History of allogeneic organ transplant.
15. History of hypersensitivity to durvalumab or any excipient.
16. Uncontrolled intercurrent illness
17. Known history of active tuberculosis.
18. Any serious or uncontrolled medical disorder or active infection non HIV, that would impair the ability of the subject to receive the treatment of protocol therapy under treating physician criteria.
19. Subjects with previous malignances, are excluded unless a complete remission was achieved at least 5 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
21. Female subjects who are pregnant, breast-feeding, male, or female patients of reproductive potential who are not employing an effective method of birth control.
22. Symptomatic or uncontrolled brain metastases
23. Subjects with uncontrolled seizures.
24. Patients with tumoral disease in the head and neck region, such as peritracheal or periesophageal lymph node involvement,
25. Patients with neuroendocrine tumors of pulmonary origin or pulmonary metastases with evidence of active bleeding
26. Patients with digestive bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Durvalumab (MEDI4736) monotherapy at the recommended dose of 1500mg every 4 weeks in solid tumors in HIV-1-infected patients	Drug: Durvalumab; 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; Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From the first dose until last follow up, assessed up to 24 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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).	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.	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.	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.	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	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	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	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.	From the inclusion date to the progression or death, due to any cause, assessed up to 24 months.

Collaborators and Investigators

• Sponsor: Spanish Lung Cancer Group
• Investigators: Principal Investigator: María González-Cao, MD, Instituto Oncológico Dr Rosell

Publications and helpful links

General Publications

• Gonzalez-Cao M, Moran T, Dalmau J, Garcia-Corbacho J, Bracht JWP, Bernabe R, Juan O, de Castro J, Blanco R, Drozdowskyj A, Argilaguet J, Meyerhans A, Blanco J, Prado JG, Carrillo J, Clotet B, Massuti B, Provencio M, Molina-Vila MA, Mayo de Las Casa C, Garzon M, Cao P, Huang CY, Martinez-Picado J, Rosell R. Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection: The Phase 2 DURVAST Study. JAMA Oncol. 2020 Jul 1;6(7):1063-1067. doi: 10.1001/jamaoncol.2020.0465.

Helpful Links

• Web page of the sponsor where users can find more information about Fundación GECP studies
• Publication of the results of DURVAST study in this article on JAMA Oncology in 2020

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): April 24, 2019
• Study Completion (Actual): March 22, 2022

Study Registration Dates

• First Submitted: March 10, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (Actual): March 29, 2017

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: HIV; HIV with cancer patient; D006678
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: GECP 16/04_DURVAST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No