This is an open-label, phase 1, first-in-human (FIH), dose-escalation, multicenter,
multinational trial evaluating the safety of oncolytic adenovirus TILT-123 as monotherapy and
in association with T-cell therapy with TILs in metastatic melanoma patients.
The primary objective of the trial is to evaluate the safety of TILT-123. The approach has
the potential to a) increase the efficacy of adoptive T-cell therapy, b) remove the need for
toxic pre- and post-conditioning regimens, c) yield the combined anti-tumor benefits of armed
oncolytic viruses and T-cell therapy.
Dose escalation of TILT-123 injection will take place between cohorts not intra-patient and
will be determined based on Dose Limiting Toxicities (DLTs).
- Signed and dated informed consent before any trial-related activities.
- Male or female, between 18-75 years of age (both included).
- Pathologically confirmed previously treated refractory or recurrent stage 3-4
melanoma, which cannot be treated with curative intent with available therapies.
- At least one prior line of medical treatment is required (for example checkpoint
inhibitors, kinase inhibitors, interleukin-2). Multiple prior therapies (e.g. surgery,
checkpoint inhibitors, kinase inhibitors, interleukin-2, interferon, chemotherapy,
radiation) are allowed.
- A > 9 mm tumor (in diameter, typically a minimum of 1 cm3 in volume) without signs of
necrosis must be available for biopsy/operation to enable growing of TILs.
- At least one additional tumor (>14 mm in diameter) must be available for injections
and biopsies for correlative analyses. The disease burden must be measurable, but does
not need to fulfil RECIST 1.1.
- Eligible for adoptive T-cell therapy with tumor infiltrating lymphocytes
- Adequate hepatic, cardiac and renal functions as following:
- Bilirubin, creatinine (serum), leukocytes, platelets; normal values.
- Haemoglobin ≥ 100 g/L.
- AST and ALT < 3 x ULN.
- 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:
- Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be
used in addition to one of the following methods: Intrauterine devices or hormonal
contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings
or long-acting injections).
- Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must
- Men: Barrier contraceptive method (i.e. condom) must be used.
- Demonstrated WHO performance score of 0-1 at screening.
- Life expectancy time longer than 3 months.
- Capable of understanding and complying with parameters as outlined in the protocol.
- BRAF negative or positive.
- Use of immunosuppressive medications (corticosteroids or drugs used in treatment of
autoimmune disease). Exempted are the following which can be allowed at screening and
during the trial: replacement corticosteroids if e.g. the patient has adrenal
insufficiency after prior immunotherapy; pulmonal and topical treatments; up to 20 mg
- History of another active invasive cancer within the past 5 years, except basalioma.
- Treated with any anti-cancer therapy for melanoma 30 days prior to enrolment.
Anti-cancer therapy for melanoma is defined as anti-cancer agents (immunotherapy,
signal-transduction inhibitors [e.g. BRAF and MEK inhibitors], cytotoxic
chemotherapy), radiotherapy and investigational agents. An investigational agent is
any drug or therapy that is currently not approved for use in humans.
- Uncontrolled cardiac or vascular diseases.
- History of heart attack or cerebral stroke within the previous 12 months before
screening or is not recovered from an older heart attack or cerebral stroke.
- LDH value > 3 x ULN.
- History of hepatic dysfunction, hepatitis or HIV.
- History of coagulation disorder.
- Any other disease which prevent participation in the opinion of the investigator.
- Female patients who are pregnant, breastfeeding or intends to become pregnant.
- Untreated brain metastases. Treated brain metastases which have not progressed in 3
months prior to screening are allowed.
- Previously treated with any oncolytic adenovirus that was administered intratumorally.
- Previously treated with adoptive cell therapy.
- Allergy to TILT-123, TIL, or ingredients present in the investigational medicinal
- Administered an investigational medicinal product or device in another clinical trial
within 30 days prior to screening