First in Human Study of T3P-Y058-739 (T3P)

NCT05120596 | Recruiting Phase 1 DMC

• 1 other identifier: T3P1001
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 15

Brief Summary

This is a first in human, phase I/II open-label, dose-finding, safety, and proof-of-concept clinical trial of T3P-Y058-739, a genetically-modified, live attenuated strain of the bacterium Yersinia enterocolitica, in patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Advanced; Solid; Tumor; Cancer; Oncology; Genetically; Bacterium; gene

Outcome Measures

Primary Outcomes (2)

• Phase 1: To assess the safety and determine the recommended phase II dose (RP2D) when given by IT injection and by IV infusion, as monotherapy and in combination with pembrolizumab.

  AEs(adverse events), SAEs(serious adverse events) will be graded by the investigator according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE Version 5.0).

  up to 45 months

• Phase 2: To assess the safety and preliminary antitumor response T3P when given by IT injection and/or IV infusion, as monotherapy and in combination with pembrolizumab.

  Response according to immune Response Evaluation Criteria in Solid Tumors (iRECIST) (Seymour et al, 2017).

  up to 45 months

Secondary Outcomes (6)

• Assessment of Duration of response (DoR)

  up to 45 months

• Assessment of progression free survival (PFS)

  up to 45 months

• To evaluate the distribution of T3P

  up to 45 months

• To evaluate the clearance of T3P

  up to 45 months

• To evaluate the shedding of T3P

  up to 45 months

Study Arms (3)

T3P-Y058-739 Intravenous (IV)

EXPERIMENTAL

Intravenous infusion

Drug: T3P-Y058-739 (IV)

T3P-Y058-739 Intratumoural (IT)

EXPERIMENTAL

Intratumoural injection

Drug: T3P-Y058-739 (IT)

T3P-Y058-739 plus pembrolizumab

EXPERIMENTAL

Intravenous infusion

Drug: Pembrolizumab+T3P-Y058-739

Interventions

T3P-Y058-739 (IV) DRUG

Intravenous infusion

T3P-Y058-739 Intravenous (IV)

T3P-Y058-739 (IT) DRUG

Intratumoral use

T3P-Y058-739 Intratumoural (IT)

Pembrolizumab+T3P-Y058-739 DRUG

intravenous infusion or intratumoural injection

T3P-Y058-739 plus pembrolizumab

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically- or cytologically-proven advanced, unresectable solid tumour for which there is no curative therapy and no alternative therapy is felt to be appropriate.
• At least one measurable lesion
• Male or female, 18 years of age or older at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Estimated life expectancy of ≥12 weeks.
• Resolution of all acute reversible toxic effects of prior therapy or surgical procedure to baseline or Grade ≤1 (except alopecia).
• Adequate iron stores without significant iron overload
• Adequate organ function
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
• At least one lesion that is measurable according to iRECIST/RECIST 1.1 and amenable to direct IT injection, i.e., a lesion that is visible, palpable, or detectable by ultrasound, and accessible for direct IT injection (injection via an endoscope is not allowed for Part A at least; ultrasound and/or radiological guidance is allowed).

You may not qualify if:

• Current or prior malignancy that could affect compliance with the protocol or interpretation of results. Patients curatively treated more than 2 years prior to enrolment, and patients with adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, are generally eligible.
• Known central nervous system (CNS) metastases.
• Patients who have previously received an allogeneic bone marrow or stem cell transplant or with congenital or acquired immunodeficiency or receiving immunosuppressive therapy (including any dose of systemic corticosteroids). Patients should have recovered immunologically from any prior immunomodulatory therapies such as CD20-targeted antibodies. Patients receiving inhaled corticosteroids for asthma or chronic obstructive pulmonary disease, and patients on steroid replacement therapy (e.g. due to prior adrenalectomy or hypophysectomy) are eligible at the investigator's discretion. Patients likely to require immunosuppressive treatment with systemic steroids or other agent (e.g., patients with frequent exacerbations of asthma) should not enter the study.
• Patients with active uncontrolled infection or known to be serologically positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Patients with recent major infection (such as pneumonia in the previous 4 weeks) should have recovered to preillness levels with resolution of reversible infection-related symptoms for at least one week prior to starting T3P.
• Patients with a documented Yersinia infection in the 12 weeks prior to treatment or with detectable Y. enterocolitica in a baseline stool sample (based on routine culture at site).
• Patients who have recently received antibiotics that could affect the viability of T3P (at least 5 half-lives should have elapsed since the last dose).
• Patients with known cardiac valvular disease or arterial aneurysms, artificial heart valves and other implanted prostheses (such as joint replacements) that cannot be easily removed or replaced. Patients with central venous access devices are allowed in the study but T3P should be administered by peripheral vein, whenever possible. Patients with a history of bacterial endocarditis, regardless of the organism, are excluded from the study.
• Patients with a history of clinically significant autoimmune conditions, major cardiac arrhythmia or ischaemia, requiring any form of regular or "as needed" medication to control symptoms, New York Heart Association class II, III or IV cardiac failure or coronary angioplasty in the previous 6 months.
• Patients who are allergic to chloramphenicol or to all of the following antibiotics: co-trimoxazole, doxycycline, ceftriaxone and cefotaxime.
• History of hypersensitivity to desferrioxamine
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or T3P administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study. This includes patients on treatment with anticoagulants within 6 months prior to study entry for thromboembolic events.
• Patients with a bleeding diathesis or receiving therapeutic doses of anticoagulants unless the lesion(s) to be injected are superficial and at low risk of bleeding. Patients receiving lower doses of anticoagulants, aspirin or clopidogrel may be eligible at the investigator's discretion, depending on the site of lesions to be injected and perceived risk of bleeding.
• Previous severe hypersensitivity reaction to treatment with Check Point Inhibitor (CPI) or other monoclonal antibody.
• History of severe immune-related adverse effects (irAEs) for greater than 12 weeks. CPI-related AEs (including irAEs) must have resolved back to Grade 0-1 and patients received no corticosteroids for irAEs for at least two weeks prior to first dose of pembrolizumab in the study.
• History of interstitial lung disease or prior pneumonitis requiring systemic corticosteroid therapy. In case of uncertainty, a high-resolution computed tomography (HRCT) should be performed at baseline.

Sponsors & Collaborators

• T3 Pharmaceuticals AG: lead

Study Sites (15)

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

RECRUITING

Institut Catala D'oncologia

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Clinica Universidad de Navarra

Madrid, 28027, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

START Madrid-CIOCC Hospital Univ. HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

Hospital Clínico Universitario de Valencia (INCLIVA)

Valencia, 46010, Spain

RECRUITING

University Hospital Bern (Inselspital)

Bern, 3010, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)

Lausanne, 1011, Switzerland

RECRUITING

University Hospital of Zürich (Universitätsspital Zürich)

Zurich, 8091, Switzerland

RECRUITING

Cancer Research UK Clinical trials; Unit Partner in CaCTUS- Cancer clinical trials Unit Scotland; Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

Leeds Clinical Research Facility

Leeds, LS9 7TF, United Kingdom

RECRUITING

Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Chief Medical Officer (CMO)

CONTACT

+4178.3060080; T3P1001@t3pharma.com

Head Clinical Operations

CONTACT

+4179.355.9741

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose-finding, safety, and proof-of-concept study

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: November 15, 2021
• Study Start: April 26, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): October 15, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CH (3); ES (8); GB (4)