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Pembrolizumab in Treating Patients with Metastatic or Locally Advanced Anal Cancer That Cannot Be Removed by Surgery

Trial Status: Active

This phase II trial studies how well pembrolizumab works in treating patients with anal cancer that has spread to other places in the body or that has spread from its original site of growth to nearby tissues or lymph nodes and cannot be removed by surgery. 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.

Inclusion Criteria

  • Participants must have metastatic or locally advanced incurable anal cancer that has been histologically confirmed; patients with locally advanced anal cancer must have had cancer recurrence after chemoradiation and must be unresectable
  • There is no limit to the number of prior therapies
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on RECIST 1.1
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the sponsor
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Demonstrate adequate organ function, all screening labs must be performed within 10 days of treatment initiation; labs must meet eligibility criteria within 4 days of cycle 1 day 1
  • Absolute neutrophil count (ANC) >= 1,500 /mcL
  • Platelets >= 80,000/mcL
  • Hemoglobin >= 8.5 g/dL or >= 5.6 mmol/L
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases
  • Albumin >= 2.8 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria

  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment; subjects requiring systemic steroids are excluded from the trial; the use of physiologic doses of corticosteroids may be approved after discussion with the sponsor
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent * Note: subjects with =< grade 2 neuropathy and alopecia are an exception to this criterion and may qualify for the study * Note: if subject received major surgery, they must wait >= 3 weeks prior to starting study treatment; they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has 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
  • Has an active infection requiring systemic therapy
  • Patients that require supplemental oxygen are excluded
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Human immunodeficiency virus (HIV)+ positive patients are eligible if their CD4+ count >= 300/uL and they have an undetectable viral load; in addition, they must be currently receiving highly active antiretroviral therapy (HAART) and be under the care of an infectious diseases specialist
  • Patients with hepatitis B and hepatitis C must be under the care of viral hepatitis expert consultant; patients with hepatitis B are required to be treated with anti-hepatitis B virus (HBV) treatment (e.g., entecavir); patients with hepatitis C need to have received prior and/or ongoing hepatitis C treatment
  • Has received a live vaccine within 30 days of planned start of study therapy; Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis


Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: Benjamin Louis Schlechter
Phone: 617-667-3725
Brigham and Women's Hospital
Status: ACTIVE
Contact: James Mark Cleary
Phone: 617-632-6073
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: James Mark Cleary
Phone: 617-632-6073
Massachusetts General Hospital Cancer Center
Status: ACTIVE
Contact: Jeffrey W. Clark
Phone: 617-643-3415


Seattle Cancer Care Alliance
Status: ACTIVE
Contact: James Mark Cleary
Phone: 617-632-6073


I. Evaluate the response rate, by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, of pembrolizumab in metastatic anal cancer patients.


I. Evaluate the response rate, by RECIST 1.1, of pembrolizumab in metastatic anal cancer patients who are PD-L1 positive.

II. Evaluate the durability of pembrolizumab response in PD-L1 positive metastatic anal cancer patients by measuring median overall survival and median progression free survival.

III. Evaluate the safety and tolerability of pembrolizumab administered every three weeks, in metastatic anal cancer.


I. Evaluate relationship between response rate, by RECIST 1.1, and potential predictive biomarkers.


Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 12 weeks thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
James Mark Cleary

  • Primary ID 16-301
  • Secondary IDs NCI-2016-01563
  • ID NCT02919969