Clinical Trials /

TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma

NCT04217473

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 in Melanoma Patients Receiving Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes

Clinical Trial IDs

  • ORG STUDY ID: TILT-T215
  • NCT ID: NCT04217473

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
TILT-123TILT-123

Purpose

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.

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).
    

Trial Arms

NameTypeDescriptionInterventions
TILT-123ExperimentalPatients 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.
  • TILT-123

Eligibility Criteria

        Inclusion Criteria:

          -  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
             be used.

          -  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.

        Exclusion Criteria:

          -  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.

          -  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
             products.

          -  Administered an investigational medicinal product or device in another clinical trial
             within 30 days prior to screening
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.
Time Frame:36 days
Safety Issue:
Description:Any clinically significant adverse changes on the ECG will be reported as Adverse Events.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:TILT Biotherapeutics Ltd.

Trial Keywords

  • oncolytic virus
  • T-cell therapy
  • immunotherapy
  • TILT

Last Updated

May 14, 2020