Oncolytic Adenovirus TILT-123 and Avelumab for Treatment of Solid Tumors Refractory to or Progressing After Anti-PD(L)1

NCT05222932 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: TILT-T776
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase 1, dose-escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with avelumab in patients with advanced solid tumors refractory to or progressing after anti-PD(L)1.

Conditions

Melanoma; Head and Neck Squamous Cell Carcinoma

Keywords

oncolytic virus; immunotherapy; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (4)

• Number of Participants with any (serious and non-serious) Adverse Events.

  Safety I

  85 days

• Number of Participants with abnormal laboratory values.

  Safety II

  85 days

• Number of Participants with vital sign abnormalities.

  Safety III

  85 days

• Number of Participants with Adverse Events assessed by 12- lead electrocardiograms (ECGs)

  Safety IV

  85 days

Study Arms (1)

TILT-123 and avelumab

EXPERIMENTAL

Patients will receive multiple administrations of TILT-123 and avelumab. 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; Drug: Avelumab

Interventions

TILT-123 BIOLOGICAL

TNFalpha and IL-2 coding oncolytic adenovirus TILT-123

Also known as: TNFalpha and IL-2 coding oncolytic adenovirus TILT-123, Ad5/3-E2F-d24-hTNFa-IRES-hIL2

TILT-123 and avelumab

Avelumab DRUG

Anti-PDL1 antibody

Also known as: anti-PD-L1 monoclonal antibody

TILT-123 and avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be over 18 years of age
• 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.
• 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.
• 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.
• The disease burden must be evaluable, but does not need to fulfil RECIST 1.1
• 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
• Patients must have experienced unequivocally documented radiographic progression of disease during or within 6 weeks after the last dose of such treatment.
• Subject must have adequate hepatic and renal functions, including the following laboratory parameters:
• Platelets \> 75 000/mm3
• Haemoglobin ≥ 100 g/L.
• AST and ALT \< 3 x ULN.
• GFR \>60 ml/min (Cockcroft-Gault formula).
• Leukocytes (WBC) \> 3,0
• 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:

You may not qualify if:

• 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).
• 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.
• 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
• 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.
• Subject has a history of interstitial parenchymal lung disease.
• Subject has a LDH value \> 3 x ULN (melanoma)
• Subject has a history of severe hepatic dysfunction, hepatitis, HIV or other severe chronic but active infectious diseases requiring systemic therapy, e.g. tuberculosis
• Subject is using proton pump inhibitors or antibiotics during screening period
• 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
• 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.
• Subject is pregnant, breastfeeding or intend to become pregnant
• Subject has untreated brain metastases. Treated and asymptomatic brain metastases which have not progressed in 3 months prior to study entry are allowed.
• Any known or suspected allergy to TILT-123 or ingredients present in the drug product as listed in this protocol.
• 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).
• Known current alcohol or drug abuse

Sponsors & Collaborators

• TILT Biotherapeutics Ltd.: lead

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Docrates Cancer Center

Helsinki, 00180, Finland

Location

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck

Interventions

Tumor Necrosis Factor-alpha; avelumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Monokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Tumor Necrosis Factors; Blood Proteins; Proteins; Biological Factors

Study Officials

• Tuomo Alanko

  Docrates Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: open-label, single arm, dose escalation

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 3, 2022
• Study Start: March 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); FI (1)