| Eligibility |
Inclusion Criteria:
1. Male or female aged = 18 years
2. Diagnosis of histologically- or cytologically-confirmed solid tumour that is advanced
and with progression. No standard treatment exists, or the subject refuses standard
treatment. Experimental immunotherapy appears as feasible exploratory treatment option
as per investigator assessment.
3. Tumour lesion(s) accessible to serial biopsies.
4. Must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests, tumour biopsies.
5. Measurable disease according to RECIST V1.1. Previously irradiated lesions are
measurable if subsequent progression is documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
7. Life expectancy > 3 months as assessed by the investigator.
8. Adequate bone marrow, cardiopulmonary, renal and hepatic functions:
- Haemoglobin =5.6 mmol/L (= 90 g/dL) (without transfusion or erythropoietin
therapy within 4 weeks prior to therapy);
- Neutrophils =1.5 x 109/L, without growth factor stimulation within 3 weeks prior
to the blood test;
- Platelet count = 75 × 109/L;
- Serum creatinine = 1.25 times ULN or creatinine clearance =50 mL mL/min (by
CKD-EPI formula);
- Hepatic function: AST and ALT = 2.5 x ULN; (5 × ULN in the case of liver
metastases); bilirubin = 1.5 × ULN except in case of Gilbert's disease and 2 ×
ULN in case of liver metastases.
9. All subjects of childbearing potential (defined as < 2 years after last menstruation
or not surgically sterile) must have a negative highly sensitive pregnancy test at
screening (urine/serum) and agree to use highly effective method for contraception
according to the European Union (EU) Clinical Trial Facilitation Group guidance from
time of signing the informed consent form (ICF) until at least 120 days after the last
administration of trial drug. The partners of subjects with childbearing potential
must also apply contraceptive methods and are recommended not to donate sperm.
10. Ability to understand and sign the ICF.
Exclusion Criteria:
1. Has had biologic, hormonal, anti-neoplastic chemotherapy, or radiation therapy within
4 weeks prior to screening (6 weeks required for nitrosourea or mitomycin) except for
medications with half-lives <5.5 days.
2. Metastatic disease that involves major airways or blood vessels, or centrally located
mediastinal tumour masses of large volume with close relation to the mayor airways
where tumour necrosis may cause perforation or severe bleeding episodes. Primary or
metastatic intestinal disease in situ where tumour necrosis may cause gastrointestinal
perforation.
3. Use of investigational agent in the 4 weeks or 5 half-lives prior to first dose of
MBS8(1V270), whichever is shortest.
4. Major surgical procedure within 14 days prior to the first trial drug dose.
5. Has a history of another primary malignancy, except for:
- Malignancy treated with curative intent and with no known active disease within 2
years prior to first dose of MBS8(1V270).
- Adequately treated non-invasive basal skin cancer or squamous cell skin
carcinoma.
- Adequately treated uterine cervical cancer stage 1B or less.
6. Treatment with systemic immunosuppressive medication (including but not limited to
corticosteroids (>10 mg prednisone per day or equivalent, except topical or inhaled),
cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-IL-6 receptor agents
and anti-TNFa agents) within 2 weeks prior to initiation of trial treatment, or
anticipation of need for systemic immunosuppressive medication during trial treatment.
7. Treatment with androgen deprivation therapies such as luteinizing-hormone releasing
hormone (LHRH) (gonadotropin-hormone releasing hormone [GnRH]) agonists within 2 weeks
prior to initiation of trial treatment.
8. Ongoing immune-related adverse events (irAEs) and/or AEs = Grade 2 not resolved from
previous therapies except vitiligo, resolved atopy, limited psoriasis, stable
neuropathy Grade 2, hair loss, and stable endocrinopathies with substitutive hormone
therapy.
9. Has uncontrolled intercurrent or chronic illness, but not limited to, ongoing or
active infection such as hepatitis B or C, human immunodeficiency virus (HIV), immune
dysfunction such as autoimmune disease, psychiatric illness such as depression or
suicidal tendency or social situations that would limit compliance with trial
requirements.
10. Has active or history of immunologic-mediated disease, including but not limited to
myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,
rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjogren's syndrome or Guillain-Barré
syndrome.
11. Has clinically significant cardiac disease, including:
- Known congestive heart failure Grade III or IV by the New York Heart Failure
Association (see Appendix A);
- Myocardial infarction within 6 months prior to signing the ICF;
- Onset of unstable angina within 6 months prior to signing the ICF.
12. History of severe allergic episodes.
13. Known hypersensitivity to any component of MBS8(1V270).
14. Has a history of seizure disorders uncontrolled on medication.
15. Has a history of clinically significant coagulation or bleeding disorders or
abnormalities.
16. Abnormal or clinically significant coagulation parameters at the discretion of the
investigator, i.e.:
- International Normalized Ratio (INR);
- Activated Partial Thromboplastin Time (APTT). Subjects being treated with
anticoagulants are excluded if the coagulation parameters are outside the
therapeutic intervals as described in the Summary of Product Characteristics
(SmPC) for the administered treatment.
17. Women of childbearing potential who deny remaining abstinent (refrain from
heterosexual intercourse) or do not use a highly effective form of contraception that
results in a failure rate of < 1% per year during the treatment period and up 120 days
after the last trial drug administration.
18. Men of reproductive potential who deny to follow accepted contraception methods during
treatment and up to 120 days after the last trial drug administration.
19. Pregnant or lactating women.
20. 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, make administration of the trial
drugs hazardous, or make it difficult to monitor adverse effects such that it is not
in the best interest of the subject to participate, in the opinion of the treating
investigator.
21. Has an autoimmune disorder requiring immune modulating treatment (>10 mg prednisone
per day or equivalent, except topical or inhaled) during the last 2 years prior to
first dose of MBS8(1V270).
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