TUNINTIL: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
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).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: TILT-123 Patients will receive administrations of TILT-123. Patients will also receive Tumor Infiltrating Lymphocytes (TILs) during the treatment phase. Escalation to the next dose of TILT-123 level will occur when the safety data has been evaluated for all patients in the preceding dose level. |
Biological: TILT-123
TNFalpha and IL-2 coding oncolytic adenovirus TILT-123
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Outcome Measures
Primary Outcome Measures
- Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration. [36 days]
- Number of Participants with abnormal laboratory values prior to TIL administration. [36 days]
- Number of Participants with vital sign abnormalities prior to TIL administration. [36 days]
- Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events prior to TIL administration. [36 days]
Any clinically significant adverse changes on the ECG will be reported as Adverse Events.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed and dated informed consent before any trial-related activities.
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Male or female, between 18-75 years of age (both included).
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Pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies.
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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.
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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.
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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.
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Eligible for adoptive T-cell therapy with tumor infiltrating lymphocytes
Adequate hepatic, cardiac and renal functions as following:
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Platelets > 75 000/mm3
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Haemoglobin ≥ 100 g/L.
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AST and ALT < 3 x ULN.
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GFR >60 ml/min (Cockcroft-Gault formula).
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Leukocytes (WBC) > 3,0
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Bilirubin <1.5 x ULN
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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:
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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).
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Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used.
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Men: Barrier contraceptive method (i.e. condom) must be used.
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Demonstrated WHO performance score of 0-1 at screening.
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Life expectancy time longer than 3 months.
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Capable of understanding and complying with parameters as outlined in the protocol.
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BRAF negative or positive.
Exclusion Criteria:
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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 of prednisone/prednisolone.
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History of another active invasive cancer as judged by the investigator within the past 3 years except basalioma.
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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.
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Uncontrolled cardiac or vascular diseases.
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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.
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LDH value > 3 x ULN.
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History of hepatic dysfunction, hepatitis or HIV.
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History of coagulation disorder.
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Any other disease which prevent participation in the opinion of the investigator.
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Female patients who are pregnant, breastfeeding or intends to become pregnant.
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Untreated brain metastases. Treated brain metastases which have not progressed in 3 months prior to screening are allowed.
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Previously treated with any oncolytic adenovirus that was administered intratumorally.
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Previously treated with adoptive cell therapy.
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Allergy to TILT-123, TIL, or ingredients present in the investigational medicinal products.
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Administered an investigational medicinal product or device in another clinical trial within 30 days prior to screening
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | National Center for Cancer Immune Therapy Herlev Hospital, Copenhagen University | Copenhagen | Denmark | ||
2 | CHU Nantes | Nantes | France |
Sponsors and Collaborators
- TILT Biotherapeutics Ltd.
Investigators
- Principal Investigator: Inge Marie Svane, CCIT, Herlev Hospital, Copenhagen University
- Principal Investigator: Brigitte Dréno, CHU Nantes, Nantes University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TILT-T215