Testing the Addition of an Experimental Medication MK-3475 (Pembrolizumab) to Usual Anti-Retroviral Medications in Patients With HIV and Cancer

NCT02595866 | Completed Phase 1 Results

• 5 other identifiers: NCI-2015-01906s16-01365CITN-12P30CA015704U01CA154967
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 12

Brief Summary

This phase I trial studies the side effects of pembrolizumab in treating patients with human immunodeficiency virus (HIV) and malignant neoplasms that have come back (relapsed), do not respond to treatment (refractory), or have distributed over a large area in the body (disseminated). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

AIDS-Related Non-Hodgkin Lymphoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Hepatocellular Carcinoma; HIV Infection; Kaposi Sarcoma; Locally Advanced Lung Non-Small Cell Carcinoma; Locally Advanced Malignant Solid Neoplasm; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Non-Hodgkin Lymphoma; Recurrent Classic Hodgkin Lymphoma; Recurrent Malignant Neoplasm; Refractory Classic Hodgkin Lymphoma; Refractory Malignant Neoplasm; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Unresectable Melanoma

Outcome Measures

Primary Outcomes (3)

• Frequency of Observed Adverse Events (AEs)

  Will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (version 5.0 beginning April 1, 2018). Safety and tolerability will be assessed by summarizing all relevant parameters including AEs, serious AEs, laboratory tests, vital signs, and electrocardiogram measurements. All summaries will be presented for each cohort and overall. If the numbers are sufficient, the results may additionally be stratified by tumor type.

  Up to 90 days after the last dose of trial treatment, up to 2 years or 35 cycles of trial treatment.

• Incidence of Immune-related Events of Clinical Interest (irECI)

  This includes the occurrence of grade 2 or higher AEs. Will be graded using CTCAE version 4.0 (version 5.0 beginning April 1, 2018). Any AE of unknown etiology associated with study therapy will be evaluated to determine if it is possibly an ECI of a potentially immunologic etiology or related to combination antiretroviral therapy (cART). All summaries will be presented for each cohort and overall. If the numbers are sufficient, the results may additionally be stratified by tumor type.

  Up to 90 days after the last dose of trial treatment, up to 2 years or 35 cycles of trial treatment.

• Incidence of cART-related ECIs of Grade 2 or Higher AEs

  Will be graded using CTCAE version 4.0 (version 5.0 beginning April 1, 2018). Any AE of unknown etiology associated with study therapy will be evaluated to determine if it is possibly an ECI of a potentially immunologic etiology or related to cART. All summaries will be presented for each cohort and overall. If the numbers are sufficient, the results may additionally be stratified by tumor type.

  Up to 90 days after the last dose of trial treatment, up to 2 years or 35 cycles of trial treatment.

Secondary Outcomes (8)

• Objective Response Rate (Cohorts 1-3)

  Up to 2 years

• Progression-free Survival (Cohorts 1-3)

  From the first dose of study drug to progressive disease or death, whichever occurs earlier, assessed up to 25 months

• Duration of Response (Cohorts 1-3)

  Interval between the date of first response (CR/PR) and the date of progression, assessed up to 2 years

• Overall Survival (Cohorts 1-3)

  From the first dose of study drug to death due to any cause, assessed up to 3 years

• Objective Response Rate (Partial Response + Completion Response)(Kaposi Sarcoma Cohort)

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab and cART)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Patients continue receiving their recommended combination antiretroviral therapy PO QD. Cycles repeat every 21 days for up to 2 years or 35 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT and blood sample collection throughout the trial. Patients may also undergo biopsies during screening and on study.

Drug: Antiretroviral Therapy; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Pembrolizumab; Procedure: Positron Emission Tomography

Interventions

Antiretroviral Therapy DRUG

Given PO

Also known as: Anti-Retroviral Therapy, ART

Treatment (pembrolizumab and cART)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (pembrolizumab and cART)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (pembrolizumab and cART)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (pembrolizumab and cART)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, QL2107, SCH 900475, SCH-900475, SCH900475

Treatment (pembrolizumab and cART)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (pembrolizumab and cART)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven metastatic or locally advanced tumors for which no standard therapy exists, or where standard therapy has failed, or in patients otherwise ineligible for standard therapy, or for an indication that anti-PD-1 therapy has been shown to be effective in studies in HIV-uninfected participants; disease-specific criteria will be applied for certain common cancers and cancers strongly associated with HIV; however, enrollment will not be confined to these tumors
• Non-small cell lung cancer (NSCLC)
• Metastatic or locally advanced disease that progressed after at least one prior therapy
• Note: patients that have actionable molecular targets (e.g., epidermal growth factor receptor \[EGFR\], anaplastic lymphoma kinase \[ALK\], c-ros oncogene 1\[ROS1\] mutations) must have received (when indicated) prior appropriate targeted therapy using Food and Drug Administration (FDA)-approved agents
• AIDS-related non-Hodgkin lymphoma and other non-Hodgkin lymphoma
• Failed standard first-line therapy; and
• Failed autologous stem cell transplant if indicated for histology (i.e diffuse large B-cell lymphoma) or autologous stem cell transplant is not feasible
• Classical Hodgkin lymphoma
• Relapsed or refractory de novo classical Hodgkin lymphoma having failed standard first-line therapy; and
• May have failed to achieve a response or progressed after treatment with brentuximab vedotin or may be brentuximab vedotin naive but is ineligible or unable to receive brentuximab vedotin; and
• May have failed to achieve a response to, progressed after, or is ineligible for autologous stem cell transplant (auto-SCT)
• Hepatocellular carcinoma (HCC)
• Not eligible for curative attempt resection or liver transplant
• Kaposi sarcoma impacting physical and/or psychological wellbeing and not amenable to local therapy. Patients who have received prior therapy and treatment naive patients are both potentially eligible to participate.
• On antiretrovival therapy (ART) with suppressed HIV viral load for \> 3 months (Note: an extended washout period is needed to avoid treatment during the period of risk for the highly toxic and often fatal "Immune Reconstitution Inflammatory Syndrome (IRIS)"

You may not qualify if:

• Active systemic immunosuppressive therapy
• Systemic steroid therapy or steroid therapy that cannot be discontinued with more than 7 consecutive days of steroids within the prior 2 weeks
• Note: the use of prednisone or equivalent \< 0.125 mg/kg/day (absolute maximum of 15 mg/day) as replacement therapy is permitted; inhaled or topical corticosteroids are permitted
• Current or history of systemic autoimmune disease requiring systemic therapy
• The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody \[ANA\] titer or lupus anticoagulant) without associated symptoms
• Clinical evidence of vitiligo or other forms of depigmenting illness
• Mild autoimmunity not impacting the function of major organs (e.g., limited psoriasis)
• Grade 3 or 4 immune related toxicity associated with prior ipilimumab therapy that has not resolved to grade 0 or 1
• Cardiovascular disease that meets one of the following: congestive heart failure (New York Heart Association class III or IV), active angina pectoris, or recent myocardial infarction (within the last 6 months)
• Active tuberculosis (TB) or atypical mycobacterial infection:
• Patients who are undergoing systemic antibiotics for active mycobacterial infection
• Patients with TB immune reconstitution syndrome (IRIS) requiring corticosteroids
• Note: patients who are receiving treatment for latent tuberculosis (isonicotinylhydrazide \[INH\] or alternative) may be eligible after discussion with the protocol P.I.
• Cirrhosis with Child-Pugh score of B or C
• Uncontrolled hepatitis B virus (HBV) infection, defined as acute liver failure or protracted, severe course, as indicated by total bilirubin \> 3 mg/dL (or direct bilirubin \> 1.5 mg/dL), international normalized ratio \> 1.5, encephalopathy, or ascites

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Louisiana State University Health Science Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

FHCC South Lake Union

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• Lurain K, Ramaswami R, Ekwede I, Eulo V, Goyal G, Menon M, Odeny TA, Sharon E, Wagner MJ, Wang CJ, Bhardwaj N, Friedlander PA, Abdul-Hay M, Cornejo Castro EM, Labo N, Marshall VA, Miley W, Moore K, Roshan R, Whitby D, Kask AS, Kaiser J, Han E, Wright A, Yarchoan R, Fling SP, Uldrick TS. Cancer Immunotherapy Trials Network 12: Pembrolizumab in HIV-Associated Kaposi Sarcoma. J Clin Oncol. 2025 Feb;43(4):432-442. doi: 10.1200/JCO.24.00640. Epub 2024 Oct 2.

  PMID: 39356983 DERIVED

• Uldrick TS, Adams SV, Fromentin R, Roche M, Fling SP, Goncalves PH, Lurain K, Ramaswami R, Wang CJ, Gorelick RJ, Welker JL, O'Donoghue L, Choudhary H, Lifson JD, Rasmussen TA, Rhodes A, Tumpach C, Yarchoan R, Maldarelli F, Cheever MA, Sekaly R, Chomont N, Deeks SG, Lewin SR. Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy. Sci Transl Med. 2022 Jan 26;14(629):eabl3836. doi: 10.1126/scitranslmed.abl3836. Epub 2022 Jan 26.

  PMID: 35080914 DERIVED

• Uldrick TS, Goncalves PH, Abdul-Hay M, Claeys AJ, Emu B, Ernstoff MS, Fling SP, Fong L, Kaiser JC, Lacroix AM, Lee SY, Lundgren LM, Lurain K, Parsons CH, Peeramsetti S, Ramaswami R, Sharon E, Sznol M, Wang CJ, Yarchoan R, Cheever MA; Cancer Immunotherapy Trials Network (CITN)-12 Study Team. Assessment of the Safety of Pembrolizumab in Patients With HIV and Advanced Cancer-A Phase 1 Study. JAMA Oncol. 2019 Sep 1;5(9):1332-1339. doi: 10.1001/jamaoncol.2019.2244.

  PMID: 31154457 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; HIV Infections; Sarcoma, Kaposi; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Melanoma; Lymphoma, Non-Hodgkin; Recurrence; Neoplasms; Lung Neoplasms

Interventions

Antiretroviral Therapy, Highly Active; Biopsy; Specimen Handling; pembrolizumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Vascular Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Kathryn Lurain, M.D.
• Organization: HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute

kathryn.lurain@nih.gov

240-858-3257

Study Officials

• Kathryn Lurain

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: April 4, 2016
• Primary Completion: October 4, 2023
• Study Completion: March 25, 2024
• Last Updated: August 9, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-05

Locations

US (12)