Study Drug Administration:
There are 3 weeks in Cycle 1 and 2 weeks in Cycles 2 and beyond.
If participant is found to be eligible to take part in this study, they will receive ISA101
by injection on Day 1 of Cycles 1, 2, and 4. Participant will be closely watched for the
first 3 hours after each dose in order to check for any allergic reactions. Each time,
participant will receive 2 injections. One may be in participant's arm and one in their leg.
Participant will receive nivolumab by vein over 60 minutes on Day 8 of Cycle 1 and Day 1 of
Cycles 2 and beyond.
On Days 1 and 8 of Cycle 1 and Day 1 of every cycle after that:
- Participant will have a physical exam.
- Blood (about 4 teaspoons) will be drawn for routine tests.
On Day 1 of Cycle 1 and then 1 time a month after that, if participant can become pregnant,
blood (about 1 teaspoon) or urine will be collected for a pregnancy test.
At Week 11 and every 6 weeks after that, participant will have a CT scan or MRI to check the
status of the disease.
Additional Research Tests:
Blood (up to 4 teaspoons each time) will be drawn before participant begins to receive the
study treatment, before they receive ISA101 at Weeks 3 and 7, before they receive nivolumab
at Weeks 9 and 11, then every 12 weeks after that. These blood samples will be used for
biomarker tests and tests of the immune system.
Length of Treatment:
Participant may take ISA101 for up to 3 doses. Participant may continue taking nivolumab for
as long as the doctor thinks it is in their best interest. Participant will no longer be
able to take the study drug if intolerable side effects occur, or if they are unable to
follow study directions.
If the disease seems like it has gotten worse, participant may decide to continue to receive
nivolumab, if they are still eligible. It is possible the study drug may be working even
though the tumor(s) got larger. However, there are risks of continuing to receive the study
drug because the disease may actually be getting worse. This is described in the side
effects section below.
Patient's participation on the study will be over after the follow-up.
At about 30 days and 70 days after the last study drug dose, and then as often as the doctor
decides as needed, the following tests and procedures will be performed:
- Participant will have a physical exam.
- Blood (about 4 teaspoons) will be drawn for routine tests.
At about 30 days, 70 days, and every 6 weeks after that (if participant stops the study
drug[s] for reasons other than the disease getting worse), participant will have a CT or MRI
scan to check the status of the disease. If the disease gets worse, these scans will stop.
Every 3 months for up to 3 years after participant's last study drug dose, they will be
asked how they are doing (either at a visit or by phone). The calls should last about 10
This is an investigational study. ISA101 is not FDA approved or commercially available. It
is currently being used for research purposes only. Nivolumab is FDA approved to treat
certain types of melanoma in patients who no longer respond to other drugs. Combining ISA101
with nivolumab is investigational. The study doctor can explain how the study drugs are
designed to work.
Up to 28 participants will be enrolled in this study. All will take part at MD Anderson.
1. Signed Written Informed Consent: a. Subjects must have signed and dated an IRB/IEC
approved written informed consent form in accordance with regulatory and
institutional guidelines. This must be obtained before the performance of any
protocol related procedures that are not part of normal subject care. b) Subjects
must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests and other requirements of the study.
2. Target Population: a. Men and women >/= 18 years of age. b. Eastern Cooperative
Oncology Group (ECOG) performance status of </= 1. c. Subjects with histologically-
or cytologically-documented incurable Human Papillomavirus (HPV)-16 positive solid
tumors including oropharyngeal squamous cell carcinoma (OPSCC), cervical, vulvar,
vaginal, anal, penile cancer. Incurable HPV-16 solid tumors are defined as tumors
which are not curable by salvage approaches including resection and/or
re-irradiation. HPV-16 serotype will be assessed by Cervista assay.
3. Target Population: d. Subjects can be treatment nave for metastatic or incurable
locally advanced HPV-16 positive solid tumors or can have one prior line of
treatment.Patients with metastatic /recurrent oropharyngeal/anal/penile HPV-16
positive carcinomas are eligible upon progression after definitive local treatment
(usually concurrent chemoradiation) if they are not candidates for salvage surgery or
re-irradiation. These patients are also eligible after progression on first line
chemotherapy for recurrent disease. Patients with metastatic /recurrent HPV-16
positive cervical cancer are eligible after progression on or after chemotherapy
4. Target Population: e. Subjects must have measurable disease by CT or MRI per RECIST
1.1 criteria; Radiographic Tumor Assessment performed within 28 days of study
inclusion. f. Target lesions may be located in a previously irradiated field if there
is documented (radiographic) disease progression in that site. g. Subject entering
the study will need to consent for mandatory biopsy at study entrance and as an
optional procedure at week 11 and at progression for biomarker evaluation. Biopsy
should be excisional, incisional or core needle. Fine needle aspiration is
insufficient. h. Prior radiotherapy or radiosurgery must have been completed at least
2 weeks prior to start.
5. Target Population: i. All baseline laboratory requirements will be assessed and
should be obtained within -14 days of study registration. Screening laboratory values
must meet the following criteria: i) WBCs >/= 2000/uL; ii) Neutrophils >/= 1500/uL;
iii) Platelets >/= 100 x 10^3/uL; iv) Hemoglobin >/= 9.0 g/dL; v) Serum creatinine of
</= 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula).
Female CrCl= (140- age in years) x weight in kg x 0.85 72 x serum creatinine in mg/
dL. Male CrCl= (140- age in years) x weight in kg x 1.00 72 x serum creatinine in mg/
dL; vi) AST </= 1.5X ULN; vii) ALT </= 1.5X ULN; viii) Total bilirubin </= ULN
(except subjects with Gilbert Syndrome who must have total bilirubin <3.0 mg/dl).
6. Age and Reproductive Status: a) Women of childbearing potential (WOCBP) must use
method(s) of contraception for 30 days + 5 half-lives (60 days) of the study drugs.
For a teratogenic study drug and/or when there is insufficient information to assess
teratogenicity (preclinical studies have not been done), a highly effective method(s)
of contraception (failure rate of less than 1% per year) is required. Highly
effective birth control in this study is defined as a double barrier method. Examples
include a condom (with spermicide) in combination with a diaphragm, cervical cap, or
intrauterine device (IUD). The individual methods of contraception should be
determined in consultation with the investigator. b) WOCBP must have a negative serum
or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG)
within 24 hours prior to the start of investigational product.
7. Age and Reproductive Status: c) Women must not be breastfeeding. d) Men who are
sexually active with WOCBP must use any contraceptive method with a failure rate of
less than 1% per year. The investigator shall review contraception methods and the
time period that contraception must be followed. Men that are sexually active with
WOCBP must follow instructions for birth control for a period of 90 days plus the
time required for the investigational drug to undergo 5 half-lives (60 days).
1. Target Disease Exceptions: a. Subjects with active CNS metastases are excluded.
Subjects are eligible if CNS metastases are adequately treated and subjects are
neurologically returned to baseline (except for residual signs or symptoms related to
the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects
must be either off corticosteroids, or on a stable or decreasing dose of </= 10 mg
daily prednisone (or equivalent) for 2 weeks. b. Subjects with carcinomatous
2. Medical History and Concurrent Diseases: a. Subjects with active, known or suspected
systemic autoimmune disease. Subjects with vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune thyroiditis only requiring hormone
replacement, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll. b. Subjects with a condition requiring systemic
treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of start. Inhaled or topical steroids,
and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are
permitted in the absence of active autoimmune disease.
3. Medical History and Concurrent Diseases: c. Prior therapy with anti-PD-1, anti-PD-L1,
anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways). d. Subjects with a history of interstitial lung disease. e. Other active
malignancy requiring concurrent intervention. f. Subjects with previous malignancies
(except non-melanoma skin cancers, and the following in situ cancers: bladder,
gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded
unless a complete remission was achieved at least 2 years prior to study entry AND no
additional therapy is required during the study period.
4. Medical History and Concurrent Diseases: g. Subjects with toxicities attributed to
prior anti-cancer therapy other than alopecia and fatigue that have not resolved to
grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. h.
Subjects who have not recovered from the effects of major surgery or significant
traumatic injury at least 14 days before the first dose of study treatment. i.
Treatment with any investigational agent within 28 days of first administration of
5. Physical and Laboratory Test Findings: a) Known history of testing positive for human
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). b)
Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
ribonucleic acid (HCV RNA) indicating acute or chronic infection.
6. Allergies and Adverse Drug Reaction: a) History of severe hypersensitivity reactions
to other monoclonal antibodies. b) History of allergy or intolerance (unacceptable
adverse event) to study drugs components.
7. Sex and Reproductive Status: a) WOCBP who are pregnant or breastfeeding. b) Women
with a positive pregnancy test at enrollment or prior to administration of study
8. Prohibited Treatments and/or Restricted Therapies: a) Ongoing or planned
administration of anti-cancer therapies other than those specified in this study. b)
Use of corticosteroids or other immunosuppressive medications as per Exclusion
9. Other Exclusion Criteria: a) Any other serious or uncontrolled medical disorder,
active infection, physical exam finding, laboratory finding, altered mental status,
or psychiatric condition that, in the opinion of the investigator, would limit a
subject's ability to comply with the study requirements, substantially increase risk
to the subject, or impact the interpretability of study results. b) Prisoners or
subjects who are involuntarily incarcerated. c) Subjects who are compulsorily
detained for treatment of either a psychiatric or physical (eg, infectious disease)
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both