Clinical Trial Finder

Comments

Trial only in the U.K, several locations, only for patients with MSI-H/MMRd or high tumour mutational burden (TMB, defined as ≥10 mut/Mb) cancer (not MSS).

Patients will receive atezolizumab (anti PD-L1, immunotherapy), brand name Tecentriq.

Contacts

Inclusion Criteria

THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 02 (ATEZOLIZUMAB) OUTLINED BELOW*

*When atezolizumab-specific inclusion/

Exclusion Criteria

exclusion criteria or precautions below differ from those specified in the Master Protocol, the atezolizumab-specific criteria will take precedence.

Inclusion Criteria:

A. Confirmed diagnosis of a malignancy that is high TMB (defined as ≥10 mut/Mb), MSI-high or of proven (previously diagnosed) CMMRD disposition using an analytically validated method.

B. Women of childbearing potential are eligible provide they meet the following criteria:

* Have a negative serum or urine pregnancy test before enrolment and;
* Agree to use one form of effective birth control method such as:

I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation ([oral, intravaginal or transdermal]);

II. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable);

III. intrauterine device (IUD),

IV. intrauterine hormone-releasing system (IUS),

V. bilateral tubal occlusion,

VI. vasectomised partner,

VII. sexual abstinence,

VIII. male or female condom with or without spermicide;

IX. cap, diaphragm or sponge with spermicide.

Effective from the first administration of atezolizumab, throughout the trial and for five months after the last administration of atezolizumab.

C. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of atezolizumab, throughout the trial until the last administration of atezolizumab:

* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence.
* Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception.
* Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.

All male patients must refrain from donating sperm for the same period.

D. Patients must be able and willing to undergo a fresh tissue biopsy.

E. ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the patient's eligibility.

Haemoglobin (Hb): ≥90 g/L (transfusion allowed)

Lymphocyte count: ≥0.5 × 10^9/L

Absolute neutrophil count (ANC): ≥1.5 × 10^9/L (no granulocyte colony-stimulating factor [GCSF] support in preceding 72 hours)

Platelet count: ≥100 × 10^9/L

Bilirubin: <1.5 × upper limit of normal (ULN). Patients with known Gilbert disease: total bilirubin ≤3 × ULN

Serum albumin: ≥25 g/L (2.5 g/dL)

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5 × ULN or ≤5 × ULN if raised due to metastases

Coagulation - prothrombin (PT) (or international normalized ratio [INR]) and activated partial thromboplastin clotting time (aPTT): ≤1.5 × ULN (unless patient is on anticoagulants, e.g. warfarin [INR should be stable and within indicated therapeutic range] or direct oral anticoagulants [DOAC]).

Amylase: ≤1.5 × ULN

Estimated glomerular filtration rate (eGFR): ≥30 mL/min

F. PAEDIATRIC PATIENTS (