CLINICAL TRIAL / NCT02743819
Pembrolizumab and Ipilimumab After Prior Immunotherapy for Melanoma
- Interventional
- Active
- NCT02743819
Contact Information
Phase II Study of Pembrolizumab and Ipilimumab Following Initial Anti-PD1/L1 Antibody
Phase II study evaluating the benefit of the combination of anti-PD1 (pembrolizumab) and anti-CTLA4 (ipilimumab) antibodies in advanced melanoma. The study will determine the response rate of the combination and evaluate other clinical parameters such as progression-free survival and safety of the combination following anti-PD1/L1 antibody. The study will also provide the opportunity to investigate blood or tumor based factors that may predict response to anti-PD1 antibody in combination with anti-CTLA4.
Primary 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
1. To summarize the progression-free survival (RECIST v1.1 and irRC) of the combination
following prior treatment with anti-PD1/L1 antibody.
2. To assess the safety of the combination following prior treatment with anti-PD1/L1
antibody.
Exploratory Objective:
To evaluate changes in the tumor microenvironment and other biospecimens before and after
adding ipilimumab to pembrolizumab.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent for the trial.
2. Be 18 years of age on day of signing informed consent.
3. 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 or disease progression within 6 months of adjuvant
anti-PD1 antibody.
4. Have measurable disease based on irRECIST 1.1.
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined below, all screening labs should be
performed within 10 days of treatment initiation.
Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL
Hemoglobin ≥8 g/dL or ≥4.96 mmol/L
Renal Serum creatinine OR Measured or calculated creatinine clearance ≤1.5 X upper
limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X
institutional ULN (GFR can also be used in place of creatinine or CrCl)
Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects
with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X
ULN for subjects with liver metastases Albumin >2.5 mg/dL
Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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
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
7. Female subject 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.
8. Female subjects 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.
Subjects of childbearing potential are those who have not been surgically sterilized
or have not been free from menses for > 1 year.
9. Male subjects 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:
The subject must be excluded from participating in the trial if the subject:
1. 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.
2. 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.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. 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 who has not recovered (i.e., ≤ Grade 1 or at baseline) from
adverse events due to agents administered more than 4 weeks earlier.
6. 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 are an exception to this criterion and
may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.
7. 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.
8. 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.
9. 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.
10. Patients with uveal/ocular melanoma are excluded.
11. Has known history of, or any evidence of active, non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. 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.
16. Has received prior therapy with an anti-CTLA4 agent.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
19. 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 are live attenuated vaccines, and
are not allowed.