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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT05120596

Studienbeginn:
April 2022

Letztes Update:
09.05.2023

Wirkstoff:
Pembrolizumab+T3P-Y058-739, T3P-Y058-739 (IV), T3P-Y058-739 (IT)

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
T3 Pharmaceuticals AG

Collaborator:
-

Kontakt

Studienlocations
(3 von 5)

Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)
1011 Lausanne
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Berangere Midez
Phone: +41 (0)21 314 52 26
E-Mail: berangere.midez@chuv.ch» Ansprechpartner anzeigen
University Hospital of Zürich (Universitätsspital Zürich)
8091 Zürich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Julia Pueschel
Phone: +41 44 255 94 85
E-Mail: Julia.Pueschel@usz.ch» Ansprechpartner anzeigen
Cancer Research UK Clinical trials; Unit Partner in CaCTUS- Cancer clinical trials Unit Scotland; Beatson West of Scotland Cancer Centre
G12 0YN Glasgow
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Victoria Withers
Phone: +44 0141 301 7224
E-Mail: Victoria.Withers@ggc.scot.nhs.uk» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

The study, which has a modular design with up to 6 parts, anticipates enrolling approximately

100 participants. Part A will open first. Part B and subsequent parts will open later. The

study will evaluate T3P-Y058-739 monotherapy given by intratumoural (IT) injection (Part A)

and by intravenous (IV) infusion (Part B). In addition, either IT or IV T3P-Y058-739 (route

of administration to be chosen based on emerging data) will be evaluated in combination with

pembrolizumab. All patients will receive low doses of desferrioxamine (which provides iron in

a form that can be used by the bacteria) to support bacterial survival and growth. All

patients will receive antibiotics on completion of therapy to eradicate any residual

T3P-Y058-739.

Ein-/Ausschlusskriterien

Inclusion Criteria:

All patients, all parts of the study

1. Histologically- or cytologically-proven advanced, solid tumour that cannot be removed

surgically and 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:

All patients, all parts of the study

1. 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, New York Heart Association class III/ 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. 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.

11. Previous severe hypersensitivity reaction to treatment with Check Point Inhibitor

(CPI) or other monoclonal antibody.

12. 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.

13. 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.

14. Patients at high risk of bowel perforation, history of acute diverticulitis,

intra-abdominal abscess or abdominal carcinomatosis).

Studien-Rationale

Primary outcome:

1. 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. (Time Frame - up to 45 months):
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).

2. 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. (Time Frame - up to 45 months):
Response according to immune Response Evaluation Criteria in Solid Tumors (iRECIST) (Seymour et al, 2017).

Secondary outcome:

1. Assessment of Duration of response (DoR) (Time Frame - up to 45 months):
DoR and PFS according to RECIST 1.1 (Eisenhauer et al, 2009) or modified criteria for selected malignancies, as appropriate(e.g., Verslype et al, 2012 for hepatocellular carcinoma).

2. Assessment of progression free survival (PFS) (Time Frame - up to 45 months):
PFS according to RECIST 1.1 (Eisenhauer et al, 2009) or modified criteria for selected malignancies, as appropriate(e.g., Verslype et al, 2012 for hepatocellular carcinoma).

3. To evaluate the distribution of T3P (Time Frame - up to 45 months):
Microbiological culture and/or quantitative polymerase chain reaction (qPCR) of samples of blood, urine, stool and (in patients with tumor's close to or involving the oropharynx) saliva.

4. To evaluate the clearance of T3P (Time Frame - up to 45 months):
Shedding will also be evaluated in swabs taken from lesions that ulcerate following T3P administration.

5. To evaluate the shedding of T3P (Time Frame - up to 45 months):
Tumor colonisation will also be evaluated in tumor biopsies (optional).

6. Assessment of Overall survival (OS) (Time Frame - Maximum 16 months of follow-up):
Overall survival (OS) (maximum 16 months of follow-up).

Studien-Arme

  • Experimental: T3P-Y058-739 Intravenous (IV)
    Intravenous infusion
  • Experimental: T3P-Y058-739 Intratumoural (IT)
    Intratumoural injection
  • Experimental: T3P-Y058-739 plus pembrolizumab
    Intravenous infusion

Geprüfte Regime

  • Pembrolizumab+T3P-Y058-739:
    intravenous infusion or intratumoural injection
  • T3P-Y058-739 (IV):
    Intravenous infusion
  • T3P-Y058-739 (IT):
    Intratumoral use

Quelle: ClinicalTrials.gov


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