A study of T3P-Y058-739, a genetically modified bacterial strain, in patients with advanced solid tumors

Spain, Switzerland, United Kingdom (ICTRP)

ID di studio ICTRP
NCT05120596 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
An open-label, phase I/II study of T3P-Y058-739, a genetically-modified strain of the bacterium Yersinia enterocolitica, in patients with advanced solid tumours (BASEC)

Titolo accademico
An Open-label, Phase I/II Study of T3P-Y058-739, a Genetically-modified Strain of the Bacterium Yersinia Enterocolitica, in Patients With Advanced Solid Tumours (ICTRP)

Titolo pubblico
First in Human Study of T3P-Y058-739 (T3P) (ICTRP)

Malattie studiate
Advanced Solid Tumor (ICTRP)

Intervento studiato
Drug: Pembrolizumab+T3P-Y058-739Drug: T3P-Y058-739 (IV)Drug: T3P-Y058-739 (IT) (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Inclusion Criteria:

1. Histologically- or cytologically-proven advanced, unresectable solid tumour for
which there is no curative therapy and no alternative therapy is felt to be
appropriate.

2. At least one measurable lesion

3. Male or female, 18 years of age or older at the time of signing informed consent.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

5. Estimated life expectancy of =12 weeks.

6. Resolution of all acute reversible toxic effects of prior therapy or surgical
procedure to baseline or Grade =1 (except alopecia).

7. Adequate iron stores without significant iron overload

8. Adequate organ function

9. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF).

10. 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).

Exclusion Criteria:

1. 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.

2. Known central nervous system (CNS) metastases.

3. 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.

4. 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.

5. 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).

6. 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).

7. 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.

8. 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.

9. Patients who are allergic to chloramphenicol or to all of the following antibiotics:
co-trimoxazole, doxycycline, ceftriaxone and cefotaxime.

10. History of hypersensitivity to desferrioxamine

11. 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.

12. 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.

13. Previous severe hypersensitivity reaction to treatment with Check Point Inhibitor
(CPI) or other monoclonal antibody.

14. 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.

15. 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.

16. Patients at high risk of bowel perforation, history of acute diverticulitis,
intra-abdominal abscess or abdominal carcinomatosis). (ICTRP)

non disponibile

Endpoint primari e secondari
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.;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. (ICTRP)

Assessment of Duration of response (DoR);Assessment of progression free survival (PFS);To evaluate the distribution of T3P;To evaluate the clearance of T3P;To evaluate the shedding of T3P;Assessment of Overall survival (OS) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Chief Medical Officer (CMO), T3P1001@t3pharma.com, +4178.3060080 (ICTRP)

ID secondari
T3P1001 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT05120596 (ICTRP)