| Eligibility |
Inclusion Criteria:
1. Target Disease Exception
1. The subject must sign and date the IRB/IEC approved written informed consent form
prior to the performance of any study-related procedures that are not considered
part of standard of care.
2. Consent for tumor biopsy samples. i. Subject must consent and will be required to
undergo a MANDATORY pre-treatment biopsy; therefore, subjects must have a lesion
located such that the specimen can be obtained at acceptable clinical risk as
judged by the Investigator. The acquisition of existing formalin-fixed
paraffin-embedded (FFPE) tumor tissue, either a block or unstained slides, for
performance of correlative studies should also be collected if available.
Subjects unable to provide a pre-treatment tumor biopsy or do not have accessible
lesions are not eligible. If there is only one measurable lesion, and a
core-needle biopsy is done (instead of excisional), the lesion may be used as
measurable lesion. If there are more than one measurable lesions, the lesion
being biopsied should not be a target lesion. Subjects must have histologic or
cytologic confirmation of an incurable solid malignancy that is advanced
(metastatic and/or unresectable)
2. Target population
a) Subjects must have cytologic or histologic confirmation of one of the following
selected advanced (metastatic and/or unresectable) solid malignancies: i. Malignant
melanoma - Uveal melanoma is NOT eligible ii. Non-small cell lung cancer: squamous or
non-squamous histology iii. Bladder carcinoma: transitional cell carcinoma of the
urothelium involving the bladder, urethra, ureter, or renal pelvis.
b) Subjects must fall into one of these two categories: i. Cohort A (limited to max 15
subjects): candidate to treatment with one anti-PD-1 or anti-PD-L1 agent but who had
not previously been treated with anti-PD-1 or anti-PD-L1 in the
metastatic/unresectable setting.
ii. Cohort B (limited to max 15 subjects): subjects who are treated continuously for
at least 4 months with one anti-PD-1 or anti-PD-L1 agent in the
metastatic/unresectable setting, without unequivocal objective response or disease
progression, and who qualify for continued treatment with the same agent, who accept a
second biopsy.
c) At least one measurable parameter according to RECIST 1.1.
d) ECOG performance status of 0 or 1
e) Life expectancy of >12 weeks at the time of informed consent per Investigator
assessment
f) Adequate organ function as defined by the following hematological and biochemical
criteria:
a. AST and ALT =2,5 X ULN or =5 X ULN with liver metastases b. Serum total bilirubin
=1,5 X ULN or direct bilirubin = ULN for patient with total bilirubin level > 1,5 ULN
c. Serum creatinine =1,5 X ULN d. ANC (Absolute Neutrophil Count) =1,000/mcL e.
Platelets = 75,000 /mcL f. Hemoglobin = 9 g/dL eller = 5.6 mmol/L
3. Age and reproductive status:
1. Age = 18
2. Women must not be breastfeeding
3. Women of childbearing potential: a negative pregnancy test is mandatory within 72
hours prior to the start of study drug
4. Woman: Agree to use contraceptive methods with a failure rate of < 1 % per year during
the treatment period and for at least 150 days after the study treatment. Safe
contraceptive methods for women are birth control pills, intrauterine device,
contraceptive injection, contraceptive implant, contraceptive patch or contraceptive
vaginal ring.
5. Men: if sexually active with women of childbearing potential, agree to use
contraceptive measures; agree to refrain from donating sperm
Exclusion Criteria:
1. Target Disease Exception
a) Subjects with known or suspected CNS metastases or with the CNS as the only site of
active disease are excluded with the following exceptions: i. Subjects with controlled
brain metastases will be allowed to enroll. Controlled brain metastases are defined as
those with no radiographic progression for at least 4 weeks after radiation and/or
surgical treatment at the time of consent. Subjects must have been off of steroids for
at least 2 weeks prior to informed consent, and have no new or progressive
neurological signs and symptoms.
2. Medical History and Concurrent Diseases
1. Subjects with an active, known or suspected autoimmune disease. Subjects with
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic
treatment, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll.
2. Prior malignancy active within the previous 3 years except for locally curable
cancers that have been apparently cured, such as basal or squamous cell skin
cancer, or carcinoma in situ of the prostate, cervix, or breast.
3. A known or underlying medical condition that, in the opinion of the Investigator
or Sponsor, could make the administration of study drug hazardous to the subject
or could adversely affect the ability of the subject to comply with or tolerate
study
4. Requirement for daily supplemental oxygen
5. The patient has a history of pneumonitis, organ transplant, human
immunodeficiency virus positive, active hepatitis B or hepatitis C
6. Any of the following medications or procedures:
i. Within 2 weeks prior to time of treatment initiation: I. Systemic or topical
corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent).
Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune disease.
II. Palliative radiation or gamma knife radiosurgery ii. Within 4 weeks prior to time
of treatment initiation: I. Any anticancer drug II. Any vaccine or adjuvant III.
Allergen hyposensitization therapy IV. Growth factors V. Major surgery, or the subject
has not recovered from surgery at the time of treatment initiation
g) The subject has not recovered to grade 0-1 from adverse events due to prior
chemotherapy, radioactive or biological cancer therapy
h) History of life-threatening or severe immune related adverse events on treatment
with another immunotherapy and is considered to be at risk of not recovering
i) The subject is expected to require any other form of systemic antineoplastic
therapy while receiving the treatment
j) Any condition that will interfere with patient compliance or safety (including but
not limited to psychiatric or substance abuse disorders)
k) Known, suspected or anticipated side effects to vaccine adjuvants
l) Significant medical disorder according to investigator; e.g. severe asthma or
chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes
mellitus
m) Concurrent treatment with other experimental drugs
n) Severe allergy or anaphylactic reactions earlier in life
3. Other exclusion criteria
1. The patient is unable to voluntarily agree to participate
2. Prisoners or subjects who are involuntarily incarcerated
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