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

• ClinicalTrials.gov Identifier: NCT04217473
• Recruitment Status: Recruiting
• First Posted: January 3, 2020
• Last Update Posted: December 20, 2021
• Sponsor: TILT Biotherapeutics Ltd.
• Information provided by (Responsible Party): TILT Biotherapeutics Ltd.

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
Metastatic Melanoma	Biological: TILT-123	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: open-label, single arm, dose escalation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 26, 2020
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration. [ Time Frame: 36 days ]
2. Number of Participants with abnormal laboratory values prior to TIL administration. [ Time Frame: 36 days ]
3. Number of Participants with vital sign abnormalities prior to TIL administration. [ Time Frame: 36 days ]
4. Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events prior to TIL administration. [ Time Frame: 36 days ]
   Any clinically significant adverse changes on the ECG will be reported as Adverse Events.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

   • 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 as judged by the investigator within the past 3 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

Contacts and Locations

Contacts

Contact: Herlev Hospital; +45 38 68 38 68; herlevhospital@regionh.dk

Locations

Denmark

National Center for Cancer Immune Therapy Herlev Hospital, Copenhagen University; Recruiting

Copenhagen, Denmark

Principal Investigator: Inge Marie Svane

France

CHU Nantes; Recruiting

Nantes, France

Principal Investigator: Brigitte Dréno

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Havunen R, Kalliokoski R, Siurala M, Sorsa S, Santos JM, Cervera-Carrascon V, Anttila M, Hemminki A. Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1. Cells. 2021 Jan 27;10(2). pii: 246. doi: 10.3390/cells10020246.

Cervera-Carrascon V, Quixabeira DCA, Havunen R, Santos JM, Kutvonen E, Clubb JHA, Siurala M, Heiniö C, Zafar S, Koivula T, Lumen D, Vaha M, Garcia-Horsman A, Airaksinen AJ, Sorsa S, Anttila M, Hukkanen V, Kanerva A, Hemminki A. Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors. Mol Ther Oncolytics. 2020 Mar 19;17:47-60. doi: 10.1016/j.omto.2020.03.003. eCollection 2020 Jun 26.

• Responsible Party: TILT Biotherapeutics Ltd.
• ClinicalTrials.gov Identifier: NCT04217473
• Other Study ID Numbers: TILT-T215
• First Posted: January 3, 2020
• Last Update Posted: December 20, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by TILT Biotherapeutics Ltd.:

oncolytic virus; T-cell therapy; immunotherapy; TILT

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas