Clinical Trial 18933

Cancer Type: Cutaneous
Interventions:Ipilimumab; Pembrolizumab (Keytruda); Yervoy (Ipilimumab)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Nikhil Khushalani

Overview

Study Title

Phase II Study of Pembrolizumab and Ipilimumab Following Initial Anti-PD1/L1 Antibody

Summary

The main purpose of this study is to determine whether pembrolizumab in combination with ipilimumab is an effective regimen for participants who have previously received an anti-PD1 antibody such as pembrolizumab or nivolumab.

Objective

Primary Objective(s): (1) Objective: To determine the irRECIST response rate of pembrolizumab with ipilimumab following initial progression or stable disease to anti-PD1/L1 antibody (or combination not containing anti-CTLA4) in subjects with advanced melanoma. Secondary Objective(s): (1) Objective: To summarize the progression-free survival (RECIST v1.1 and irRC) of the combination following prior treatment with anti-PD1/L1 antibody. (2) Objective: To assess the safety of the combination following prior treatment with anti-PD1/L1 antibody. Exploratory Objective: (1) Objective: To evaluate changes in the tumor microenvironment and other biospecimens before and after adding ipilimumab to pembrolizumab.

Inclusion Criteria

  • Willing and able to provide written informed consent for the trial.
  • 18 years of age or older on day of signing informed consent.
  • Have experienced disease progression or stable disease lasting at least 24 weeks during treatment with an anti-PD1/L1 antibody as the treatment regimen immediately prior to accrual to this study.
  • Have measurable disease based on Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) 1.1.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate adequate organ function as defined below in the protocol, all screening labs should be performed within 10 days of treatment initiation.
  • Female participants of childbearing potential should 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 participants of childbearing potential should 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.
  • Male participants should 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 received study therapy (including investigational device) as part of a clinical trial within 4 weeks of the first dose of treatment, with the exclusion of an anti-PD1/L1 antibody given as either a single agent or non-CTLA-4 antibody containing combination.
  • Has diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of trial treatment.
  • 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 (excluding commercial or investigational anti-PD1 or anti-PD-L1 antibodies as single agents) or has not recovered (i.e., less than or equal to 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 has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Potential participants with less than or equal to Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • 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.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to first dose of trial treatment and neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis (excluded regardless of clinical stability).
  • 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Known history of, or evidence of active, non-infectious pneumonitis.
  • Active infection requiring systemic therapy.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • 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-CTLA4 agent.
  • Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • 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 allowed; intranasal influenza vaccines are live attenuated vaccines and not allowed.