| Eligibility |
Inclusion Criteria:
1. Subject must be over 18 years of age
2. Subject must have pathologically confirmed refractory or recurrent injectable solid
tumor (melanoma or SCCHN), which cannot be treated with curative intent with available
therapies and is refractory to or progressing after anti-PD(L)1 immunotherapy.
3. Standard therapy has failed, it does not exist, is not available or is unlikely to
result in meaningful clinical benefit (as assessed by the investigator). Multiple
prior therapies (eg. surgery, chemotherapy, radiation, checkpoint inhibitors, kinase
inhibitors, biological therapies) are allowed.
4. At least one tumor lesion of 15 mm or bigger must be available for biopsy and
injections that, in the opinion of the investigator, is accessible to repeated
injections and biopsies without major safety concerns.
5. The disease burden must be evaluable, but does not need to fulfil RECIST 1.1
6. Patients must have received at least 6 weeks of prior PD-1/PDL-1 blocking antibody
therapy (e.g. 3x 2w cycle or 3x 3w cycle) within the past up to 12 months
7. Patients must have experienced unequivocally documented radiographic progression of
disease during or within 6 weeks after the last dose of such treatment.
8. Subject must have adequate hepatic and renal functions, including the following
laboratory parameters:
1. Platelets > 75 000/mm3
2. Haemoglobin = 100 g/L.
3. AST and ALT < 3 x ULN.
4. GFR >60 ml/min (Cockcroft-Gault formula).
5. Leukocytes (WBC) > 3,0
6. Bilirubin <1,5 x ULN
9. Men and women must be willing to use adequate forms of contraception from screening,
during the trial, and for a minimum of 90 days after end of treatment, in accordance
with the following:
1. Women of childbearing potential: Barrier contraceptive method (i.e. condom) must
be used in addition to one of the following methods: Intrauterine device or
hormonal contraception (oral contraceptive pills, implant, transdermal patches,
vaginal ring or long-acting injections).
2. Women not of childbearing potential: Barrier contraceptive method (i.e. condom)
must be used.
3. Men: Barrier contraceptive method (i.e. condom) must be used.
10. Subject must demonstrate a WHO/ECOG performance score of 0-1
11. Subject must have life expectancy longer than 3 months according to investigator
assessment
12. Subject is capable of understanding and complying with parameters as outlined in the
protocol and able to sign and date the informed consent approved by the Independent
Ethics committee prior to the initiation of any screening or study -specific
procedure.
Exclusion Criteria:
1. Prior organ transplantation including allogenic stem-cell transplantation or subject
is using systemic immunosuppressive medications (eg. corticosteroids or drugs used in
treatment of autoimmune disease). Exempted are the following which can be allowed at
screening and during the trial: a) replacement corticosteroids if e.g. the patient has
adrenal insufficiency after prior immunotherapy b) inhaled and topical treatments c)
up to 20 mg/d of prednisone/prednisolone (or equivalent).
2. Treated with any anti-cancer therapy within 30 days prior to the first virus
injection. Anti-cancer therapy is defined as anti-cancer agents (e.g. cytotoxic
chemotherapy, immunotherapy, signal-transduction inhibitors, biological therapies) and
investigational agents. An investigational agent is any drug or therapy that is
currently not approved for use in humans. Continuation of bone modifying agents (eg.
bisphosphonate or denosumab) is allowed if started at least 3 months before.
Palliative radiation is not allowed within 14 days of the first virus injection
(before or after), but it is allowed after day 15 during the trial treatment period,
if deemed necessary by the investigator.
3. Subject has a history of another active invasive cancer within the past 5 years,
except curatively treated basalioma or squamous cell carcinoma of the skin
4. Clinically significant (i.e. active) cardiovascular disease: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
prior to enrollment), unstable angina, congestive heart failure (= New York Heart
Association Classification Class II), or serious cardiac arrhythmia requiring
medication.
5. Subject has a history of interstitial parenchymal lung disease.
6. Subject has a LDH value > 3 x ULN (melanoma)
7. Subject has a history of severe hepatic dysfunction, hepatitis, HIV or other severe
chronic but active infectious diseases requiring systemic therapy, e.g. tuberculosis
8. Subject is using proton pump inhibitors or antibiotics during screening period
9. Subject has a history of a coagulation disorder or abnormality in coagulation
parameters, as defined by an international normalized ratio not within the normal
range, or has received oral or parenteral anticoagulants or thrombolytic agents for
therapeutic or prophylactic purposes (including coumadin and warfarin) within 10 days
of the first dose of the study treatments. Low molecular weight heparin is permitted
if the international normalized ratio is within the normal range
10. Any other medical condition or laboratory abnormality that in the judgment of the
principal investigator, may increase the risk associated with study participation or
may interfere with interpretation of study results and /or otherwise make the patient
inappropriate for entry into this trial.
11. Subject is pregnant, breastfeeding or intend to become pregnant
12. Subject has untreated brain metastases. Treated and asymptomatic brain metastases
which have not progressed in 3 months prior to study entry are allowed.
13. Any known or suspected allergy to TILT-123 or ingredients present in the drug product
as listed in this protocol.
14. Any known or suspected allergy to avelumab or ingredients present in the drug product
as listed in summary of product characteristics (SmPC), including known severe
hypersensitivity reactions to monoclonal antibodies (NCI CTCAE Grade = 3).
15. Known current alcohol or drug abuse
16. Vaccination with live vaccines in the past 30 days prior to start of investigational
treatment
17. History of immune-related adverse events to previous immunotherapy which led to
discontinuation from treatment
|
