search
Back to results

DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition (DETERMINE)

Primary Purpose

Malignancy, Malignant Neoplasm, Lymphoproliferative Disorders

Status
Recruiting
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Atezolizumab
Sponsored by
Cancer Research UK
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignancy focused on measuring Adult, Antineoplastic Agents, Atezolizumab, Cancer, Child, Malignancy, Malignant Neoplasms, Molecular Targeted Therapy, Neoplasms by Histologic Type, Neoplasms by Site, Paediatric, Precision Medicine, Rare, Tumour-agnostic, Young adult

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

THE PARTICIPANT 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 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 and for five months after the last administration of atezolizumab: Agree to take measures not to father children by using a barrier method of contraception 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 as in B. 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. D. Patients must be able and willing to undergo a fresh biopsy. E. ADULT PATIENTS: 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/mi F. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted G. PAEDIATRIC PATIENTS (there is no lower age limit for paediatric patients): 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): ≥80 g/L (transfusion allowed) Lymphocyte Count: ≥0.5×10^9/L Absolute neutrophil count (ANC): ≥1.0×10^9/L (no GCSF support in preceding 72 hours) Platelet count: ≥75×10^9/L (unsupported for 72 hrs) Bilirubin: ≤1.5 × ULN for age with the following exception: 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 for age 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 DOAC). Amylase: ≤1.5 × ULN. Estimated glomerular filtration rate (eGFR): >60 mL/min (uncorrected value) H. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted Exclusion Criteria: A. Diagnosis of urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma or triple negative breast cancer. B. Patients with rapidly progressing or symptomatically deteriorating brain metastases. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within the 14 days prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or central nervous system (CNS) malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration. •Paediatric patients with either primary brain tumours or extracranial solid tumours with intracranial metastases with one or more intracranial lesions should only be considered for inclusion if largest intracranial lesion is ≤6 cm in longest axis. Consideration should also be given to the intracranial location of the tumour and potential risk should swelling occur. This is because of the class risk of immune checkpoint inhibitors such as atezolizumab causing immune-mediated inflammatory response and 'tumour flare' which may result in acute neurological deterioration. C. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five months following their last dose of atezolizumab. D. History or clinical evidence of current inflammatory lung disease: History of idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. Evidence of active pneumonitis on screening chest computed tomography (CT) scan. E. Active autoimmune disease that requires the use of systemic immunomodulatory therapy (i.e. with disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy for hypothyroidism and adrenal or pituitary insufficiency is acceptable. F. Ongoing lung pathologies which, in the opinion of the Investigator present a compromise to safety (e.g. active tuberculosis). G. Systemic immunomodulatory agents within 14 days prior to trial entry (immunostimulatory agents within four weeks). Exceptions to this are: Patients who received acute, low dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are eligible for the trial. Patients who received corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma equivalent to ≤10 mg prednisolone a day or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial. Patients with primary CNS disease can be receiving concurrent treatment with corticosteroids. Patients must be receiving a stable or decreasing dose for ≥14 days for adults and ≥7 days for paediatric patients prior to the screening magnetic resonance imaging (MRI) scan and at the time of drug initiation. Patients who receive physiological doses of steroid replacement (e.g. hydrocortisone) are permitted. H. Known to be serologically positive (as detected by polymerase chain reaction) for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). I. History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins including other immune checkpoint inhibitors. J. Known hypersensitivity to Chinese hamster ovary cell products. K. Known hypersensitivity to atezolizumab or any of the excipients. L. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during atezolizumab treatment or within five months after the final dose of atezolizumab. M. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or NYHA class III or IV congestive heart failure. Patients with a cerebrovascular event (including stroke or transient ischaemic attacks [TIA]) or cardiovascular event (including acute myocardial infarction [MI]) within three months before the first dose of atezolizumab. N. Prior allogeneic stem cell or solid organ transplantation on immunosuppression. O. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to atezolizumab. P. Uncontrolled diabetes. Q. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.

Sites / Locations

  • Belfast City Hospital
  • University Hospital BirminghamRecruiting
  • Birmingham Children's Hospital
  • Bristol Royal Hospital for Children
  • Bristol Haematology and Oncology Centre
  • Addenbrooke's HospitalRecruiting
  • Velindre Cancer Centre
  • Western General HospitalRecruiting
  • The Beatson Hospital
  • Royal Hospital for Children Glasgow
  • Leeds General Infirmary
  • Leicester Royal Infirmary
  • Alder Hey Hospital
  • The Royal Marsden Hospital
  • University College London HospitalRecruiting
  • Guy's HospitalRecruiting
  • Great Ormond Street Hospital
  • Royal Manchester Children's Hospital
  • The Christie HospitalRecruiting
  • Great North Children's HospitalRecruiting
  • Freeman HospitalRecruiting
  • Churchill HospitalRecruiting
  • John Radcliffe HospitalRecruiting
  • Weston Park Hospital
  • Southampton General Hospital
  • Clatterbridge Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm 02: Atezolizumab

Arm Description

This atezolizumab treatment arm is for adult, TYA and paediatric participants with cancers with high TMB or high MSI or proven (previously diagnosed) CMMRD.

Outcomes

Primary Outcome Measures

Objective Response (OR)
An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related (ir)-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria (RANO)). In patients with leukaemia, OR will be defined as the occurrence of CR , CRi (CR incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.
Durable Clinical Benefit (DCB)
DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria). Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.

Secondary Outcome Measures

Duration of response (DR)
Duration of response, is defined as the time from the date of the first confirmed CR or PR according to RECIST 1.1 or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria to the date of disease progression. The trial will report the median DR and 95% credible interval.
Best percentage change in sum of target lesion / index lesion diameters (PCSD)
PCSD is defined as the greatest decrease or least increase in the sum of target lesion diameters (RECIST) or index lesion diameters (irRECIST) as a percentage compared to the baseline measurement. The trial will report the mean PCSD and 95% credible interval.
Time to treatment discontinuation (TTD)
TTD is defined as the time from date of starting trial treatment to date of discontinuing trial treatment, in days estimated by the median of the posterior inverse gamma probability distribution. The trial will report the median TTD and 95% credible interval.
Progression-Free Survival time (PFS)
PFS is defined as the time from date of starting trial treatment to date of progression or date of death without a previous progression recorded estimated by the median of the posterior inverse gamma probability distribution.
Time to Progression (TTP)
TTP is defined as the time from date of starting trial treatment to date of progression or date of death without recorded progression censored rather than events. The trial will report the median TTP and 95% credible interval.
Growth Modulation Index (GMI)
GMI is defined as the ratio of TTP with the trial protocol treatment to TTP on the most recent prior line of therapy. The trial will report the mean GMI and 95% credible interval.
Overall Survival time (OS)
OS is defined as the time from date of starting trial treatment to date of death from any cause estimated by the median of the posterior normal probability distribution.
Occurrence of at least one Suspected Unexpected Serious Adverse Event (SUSAR)
The trial will report the number of patients who experience at least one SUSAR to atezolizumab.
Occurrence of at least one Grade 3, 4 or 5 atezolizumab related AE
Number of patients who experience at least one atezolizumab related Grade 3, 4 or 5 AE according to NCI CTCAE Version 5.0.
EORTC-QLQ-30 Standardised Area Under Summary Score Curve (QLQSAUC) in adult participants
For adult populations, multiple measures of QoL will be generated from patient completion of the European Organisation for Research and Treatment of Cancer QLQC30 (EORTC-QLQC30) questionnaire (30 measures). For each patient the Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean QLQSAUC and 95% credible interval.
EQ-5D Standardised Area Under Index Value Curve (EQ5DSAUC) in adult participants
For adult populations, two measures of QoL will be generated from patient completion of the EQ-5D-5L questionnaire. For each measure, scores based on responses from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean EQ5DSAUC and 95% credible interval.
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in paediatric participants.
For paediatric populations multiple measures of QoL will be generated from patient completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in parents from paediatric participants.
For paediatric populations multiple measures of QoL will be generated from patient's parent completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.

Full Information

First Posted
February 22, 2023
Last Updated
October 24, 2023
Sponsor
Cancer Research UK
Collaborators
University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche
search

1. Study Identification

Unique Protocol Identification Number
NCT05770102
Brief Title
DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition
Acronym
DETERMINE
Official Title
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 02: Atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High TMB or MSI-high or Proven CMMRD Disposition.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
October 2029 (Anticipated)
Study Completion Date
October 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cancer Research UK
Collaborators
University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This clinical trial is looking at a drug called atezolizumab. Atezolizumab is approved as standard of care treatment for adult patients with urothelial cancer, non-small cell lung cancer, extensive-stage breast small cell lung cancer, hepatocellular carcinoma and triple negative cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Atezolizumab works in patients with these types of cancers which have certain changes in the cancer cells called high tumour mutational burden (TMB) or high microsatellite instability (MSI) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD). Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also TMB/MSH-high or show CMMRD. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.
Detailed Description
DETERMINE Treatment Arm 02 (atezolizumab) aims to evaluate the efficacy of atezolizumab in adult, paediatric and teenage/young adult (TYA) patients with rare* cancers with high TMB or high MSI or proven CMMRD disposition and in common cancers where high TMB/MSI or proven CMMRD is considered to be infrequent. *Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded where promising activity is identified to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the participant based on molecularly-defined cohorts. Screening: Consenting participants undergo biopsy and collection of blood samples for research purposes. Treatment: Participants will receive atezolizumab until disease progression, unacceptable toxicity or withdrawal of consent. Participants will also undergo collection of blood samples at various intervals while receiving treatment and at EoT. After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignancy, Malignant Neoplasm, Lymphoproliferative Disorders, Neoplasms by Histologic Type, Neoplasms by Site, Cancer, Colorectal Neoplasms, Endometrial Neoplasms, Melanoma
Keywords
Adult, Antineoplastic Agents, Atezolizumab, Cancer, Child, Malignancy, Malignant Neoplasms, Molecular Targeted Therapy, Neoplasms by Histologic Type, Neoplasms by Site, Paediatric, Precision Medicine, Rare, Tumour-agnostic, Young adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm 02: Atezolizumab
Arm Type
Experimental
Arm Description
This atezolizumab treatment arm is for adult, TYA and paediatric participants with cancers with high TMB or high MSI or proven (previously diagnosed) CMMRD.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Adult participants will receive 1200 mg of atezolizumab intravenously every 21 days. Paediatric participants will receive atezolizumab at a dose of 15 mg/kg (maximum 1200 mg) every 21 days. Participants may continue on treatment until disease progression, unacceptable toxicity or withdrawal of consent.
Primary Outcome Measure Information:
Title
Objective Response (OR)
Description
An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related (ir)-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria (RANO)). In patients with leukaemia, OR will be defined as the occurrence of CR , CRi (CR incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.
Time Frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Title
Durable Clinical Benefit (DCB)
Description
DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria). Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.
Time Frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Secondary Outcome Measure Information:
Title
Duration of response (DR)
Description
Duration of response, is defined as the time from the date of the first confirmed CR or PR according to RECIST 1.1 or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria to the date of disease progression. The trial will report the median DR and 95% credible interval.
Time Frame
Disease assessment every 2 cycles of atezolizumab (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 3 cycles, on discussion with Sponsor. Follow-up visits are every 12 weeks after last dose of atezolizumab for up to 2 years.
Title
Best percentage change in sum of target lesion / index lesion diameters (PCSD)
Description
PCSD is defined as the greatest decrease or least increase in the sum of target lesion diameters (RECIST) or index lesion diameters (irRECIST) as a percentage compared to the baseline measurement. The trial will report the mean PCSD and 95% credible interval.
Time Frame
Disease assessment performed every 2 cycles (each cycle is 21 days). After 24 weeks, disease assessments can be repeated every 3 cycles, on discussion with Sponsor. Follow-up visits are every 12 weeks following last dose for a period of up to 2 years.
Title
Time to treatment discontinuation (TTD)
Description
TTD is defined as the time from date of starting trial treatment to date of discontinuing trial treatment, in days estimated by the median of the posterior inverse gamma probability distribution. The trial will report the median TTD and 95% credible interval.
Time Frame
From first dose of atezolizumab to discontinuation of trial treatment up to 5 years.
Title
Progression-Free Survival time (PFS)
Description
PFS is defined as the time from date of starting trial treatment to date of progression or date of death without a previous progression recorded estimated by the median of the posterior inverse gamma probability distribution.
Time Frame
Disease assessment performed every 2 cycles (each cycle is 21 days). After 24 weeks, it can be done every 3 cycles, on discussion with Sponsor. Follow-up visits take place every 12 weeks following last dose of atezolizumab for a period of up to 2 years.
Title
Time to Progression (TTP)
Description
TTP is defined as the time from date of starting trial treatment to date of progression or date of death without recorded progression censored rather than events. The trial will report the median TTP and 95% credible interval.
Time Frame
Disease assessment performed every 2 cycles (each cycle is 28 days). After 24 weeks, it can be done every 3 cycles, on discussion with Sponsor. Follow-up visits take place every 12 weeks following last dose of atezolizumab for a period of up to 2 years.
Title
Growth Modulation Index (GMI)
Description
GMI is defined as the ratio of TTP with the trial protocol treatment to TTP on the most recent prior line of therapy. The trial will report the mean GMI and 95% credible interval.
Time Frame
Disease assessment performed every 2 cycles (each cycle is 21 days). After 24 weeks, it can be done every 3 cycles, on discussion with Sponsor. Follow-up visits take place every 12 weeks following last dose of atezolizumab for a period of up to 2 years.
Title
Overall Survival time (OS)
Description
OS is defined as the time from date of starting trial treatment to date of death from any cause estimated by the median of the posterior normal probability distribution.
Time Frame
Time of death or up to 2 years after the End of Treatment (EoT) visit.
Title
Occurrence of at least one Suspected Unexpected Serious Adverse Event (SUSAR)
Description
The trial will report the number of patients who experience at least one SUSAR to atezolizumab.
Time Frame
From the time of consent until 90 days after last dose of atezolizumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
Title
Occurrence of at least one Grade 3, 4 or 5 atezolizumab related AE
Description
Number of patients who experience at least one atezolizumab related Grade 3, 4 or 5 AE according to NCI CTCAE Version 5.0.
Time Frame
From the time of consent until 90 days after last dose of atezolizumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
Title
EORTC-QLQ-30 Standardised Area Under Summary Score Curve (QLQSAUC) in adult participants
Description
For adult populations, multiple measures of QoL will be generated from patient completion of the European Organisation for Research and Treatment of Cancer QLQC30 (EORTC-QLQC30) questionnaire (30 measures). For each patient the Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean QLQSAUC and 95% credible interval.
Time Frame
QoL surveys performed at baseline every 2 cycles (every cycle is 28 days) and after interrupting treatment (up to 5 years).
Title
EQ-5D Standardised Area Under Index Value Curve (EQ5DSAUC) in adult participants
Description
For adult populations, two measures of QoL will be generated from patient completion of the EQ-5D-5L questionnaire. For each measure, scores based on responses from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean EQ5DSAUC and 95% credible interval.
Time Frame
QoL surveys performed prior to inclusion, every 2 cycles (each cycle is 21 days) and at EoT visit (up to 5 years).
Title
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in paediatric participants.
Description
For paediatric populations multiple measures of QoL will be generated from patient completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.
Time Frame
QoL surveys performed prior to inclusion, every 2 cycles (each cycle is 21 days) and at EoT visit (up to 5 years).
Title
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in parents from paediatric participants.
Description
For paediatric populations multiple measures of QoL will be generated from patient's parent completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.
Time Frame
QoL surveys performed prior to inclusion, every 2 cycles (each cycle is 21 days) and at EoT visit (up to 5 years).

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
THE PARTICIPANT 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 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 and for five months after the last administration of atezolizumab: Agree to take measures not to father children by using a barrier method of contraception 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 as in B. 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. D. Patients must be able and willing to undergo a fresh biopsy. E. ADULT PATIENTS: 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/mi F. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted G. PAEDIATRIC PATIENTS (there is no lower age limit for paediatric patients): 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): ≥80 g/L (transfusion allowed) Lymphocyte Count: ≥0.5×10^9/L Absolute neutrophil count (ANC): ≥1.0×10^9/L (no GCSF support in preceding 72 hours) Platelet count: ≥75×10^9/L (unsupported for 72 hrs) Bilirubin: ≤1.5 × ULN for age with the following exception: 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 for age 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 DOAC). Amylase: ≤1.5 × ULN. Estimated glomerular filtration rate (eGFR): >60 mL/min (uncorrected value) H. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted Exclusion Criteria: A. Diagnosis of urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma or triple negative breast cancer. B. Patients with rapidly progressing or symptomatically deteriorating brain metastases. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within the 14 days prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or central nervous system (CNS) malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration. •Paediatric patients with either primary brain tumours or extracranial solid tumours with intracranial metastases with one or more intracranial lesions should only be considered for inclusion if largest intracranial lesion is ≤6 cm in longest axis. Consideration should also be given to the intracranial location of the tumour and potential risk should swelling occur. This is because of the class risk of immune checkpoint inhibitors such as atezolizumab causing immune-mediated inflammatory response and 'tumour flare' which may result in acute neurological deterioration. C. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five months following their last dose of atezolizumab. D. History or clinical evidence of current inflammatory lung disease: History of idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. Evidence of active pneumonitis on screening chest computed tomography (CT) scan. E. Active autoimmune disease that requires the use of systemic immunomodulatory therapy (i.e. with disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy for hypothyroidism and adrenal or pituitary insufficiency is acceptable. F. Ongoing lung pathologies which, in the opinion of the Investigator present a compromise to safety (e.g. active tuberculosis). G. Systemic immunomodulatory agents within 14 days prior to trial entry (immunostimulatory agents within four weeks). Exceptions to this are: Patients who received acute, low dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are eligible for the trial. Patients who received corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma equivalent to ≤10 mg prednisolone a day or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the trial. Patients with primary CNS disease can be receiving concurrent treatment with corticosteroids. Patients must be receiving a stable or decreasing dose for ≥14 days for adults and ≥7 days for paediatric patients prior to the screening magnetic resonance imaging (MRI) scan and at the time of drug initiation. Patients who receive physiological doses of steroid replacement (e.g. hydrocortisone) are permitted. H. Known to be serologically positive (as detected by polymerase chain reaction) for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). I. History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins including other immune checkpoint inhibitors. J. Known hypersensitivity to Chinese hamster ovary cell products. K. Known hypersensitivity to atezolizumab or any of the excipients. L. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during atezolizumab treatment or within five months after the final dose of atezolizumab. M. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or NYHA class III or IV congestive heart failure. Patients with a cerebrovascular event (including stroke or transient ischaemic attacks [TIA]) or cardiovascular event (including acute myocardial infarction [MI]) within three months before the first dose of atezolizumab. N. Prior allogeneic stem cell or solid organ transplantation on immunosuppression. O. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to atezolizumab. P. Uncontrolled diabetes. Q. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aida Sarmiento Castro
Phone
+442034695101
Email
determine@cancer.org.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Krebs, Prof
Organizational Affiliation
The Christie Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Belfast City Hospital
City
Belfast
ZIP/Postal Code
BT9 7AB
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vicky Coyle, Prof
Email
V.Coyle@qub.ac.uk
First Name & Middle Initial & Last Name & Degree
Vicky Coyle, Prof
Facility Name
University Hospital Birmingham
City
Birmingham
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gary Middleton, Prof
Phone
0121 371 3573
Email
G.Middleton@bham.ac.uk
First Name & Middle Initial & Last Name & Degree
Gary Middleton, Prof
Facility Name
Birmingham Children's Hospital
City
Birmingham
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susanne Gatz, Dr
Phone
0121 333 9999
Email
Susanne.Gatz@nhs.net
First Name & Middle Initial & Last Name & Degree
Susanne Gatz, Dr
Facility Name
Bristol Royal Hospital for Children
City
Bristol
ZIP/Postal Code
BS2 8BJ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antony Ng, Dr
Phone
0117 342 8044
Email
Antony.Ng@uhbw.nhs.uk
First Name & Middle Initial & Last Name & Degree
Antony Ng, Dr
Facility Name
Bristol Haematology and Oncology Centre
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antony Ng, Dr
Phone
0117 342 8044
Email
Antony.Ng@uhbw.nhs.uk
First Name & Middle Initial & Last Name & Degree
Antony Ng, Dr
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 OQQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bristi Basu, Dr
Phone
01223 596105
Email
bb313@medschl.cam.ac.uk
First Name & Middle Initial & Last Name & Degree
Bristi Basu, Dr
Facility Name
Velindre Cancer Centre
City
Cardiff
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Jones, Dr
Phone
02920 615888
Ext
6327
Email
Robert.Hugh.Jones@wales.nhs.uk
First Name & Middle Initial & Last Name & Degree
Robert Jones, Dr
Facility Name
Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Symeonides, Dr
First Name & Middle Initial & Last Name & Degree
Stefan Symeonides, Dr
Facility Name
The Beatson Hospital
City
Glasgow
ZIP/Postal Code
G12 OYN
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Roxburgh, Dr
Phone
0141 301 7118
Email
Patricia.Roxburgh@glasgow.ac.uk
First Name & Middle Initial & Last Name & Degree
Patricia Roxburgh, Dr
Facility Name
Royal Hospital for Children Glasgow
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Milind Ronghe, Dr
Phone
0141 452 6692
Email
Milind.Ronghe@ggc.scot.nhs.uk
First Name & Middle Initial & Last Name & Degree
Milind Ronghe, Dr
Facility Name
Leeds General Infirmary
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Elliott, Dr
Phone
0113 392 8779
Email
martin.elliott1@nhs.net
First Name & Middle Initial & Last Name & Degree
Martin Elliott, Dr
Facility Name
Leicester Royal Infirmary
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Thomas, Dr
Phone
0116 2587601
Email
at107@le.ac.uk
First Name & Middle Initial & Last Name & Degree
Anne Thomas, Dr
Facility Name
Alder Hey Hospital
City
Liverpool
ZIP/Postal Code
L14 5AB
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Howell, Dr
Phone
0151 293 3679
Email
Lisa.Howell@alderhey.nhs.uk
First Name & Middle Initial & Last Name & Degree
Lisa Howell, Dr
Facility Name
The Royal Marsden Hospital
City
London Borough of Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lynley Marshall, Dr
Phone
0208 661 3678
Email
LynleyVanessa.Marshall@icr.ac.uk
First Name & Middle Initial & Last Name & Degree
Lynley Marshall, Dr
Facility Name
University College London Hospital
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Foster, Prof
Phone
020 3447 5085
Email
M.Forster@ucl.ac.uk
First Name & Middle Initial & Last Name & Degree
Martin Foster, Prof
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Spicer, Dr
Phone
020 7188 4260
Email
james.spicer@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
James Spicer, Dr
Facility Name
Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darren Hargrave, Dr
Phone
0207 813 8525
Email
Darren.hargrave@gosh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Darren Hargrave, Dr
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guy Makin, Dr
Phone
0161 701 8419
Email
Guy.Makin@mft.nhs.uk
First Name & Middle Initial & Last Name & Degree
Guy Makin, Dr
Facility Name
The Christie Hospital
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Krebs, Prof
Phone
0161 918 7672
Email
Matthew.Krebs@nhs.net
First Name & Middle Initial & Last Name & Degree
Matthew Krebs, Prof
Facility Name
Great North Children's Hospital
City
Newcastle
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alastair Greystoke, Dr
Phone
0191 2138476
Email
Alastair.Greystoke@newcastle.ac.uk
First Name & Middle Initial & Last Name & Degree
Alastair Greystoke, Dr
Facility Name
Freeman Hospital
City
Newcastle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alastair Greystoke, Dr
Phone
0191 2138476
Email
Greystoke@newcastle.ac.uk
First Name & Middle Initial & Last Name & Degree
Alastair Greystoke, Dr
Facility Name
Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Pratap, Dr
Phone
01865 235273
Email
Sarah.Pratap@ouh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Sarah Pratap, Dr
Facility Name
John Radcliffe Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Pratap, Dr
Phone
01865 235273
Email
Sarah.Pratap@ouh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Sarah Pratap, Dr
Facility Name
Weston Park Hospital
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Danson, Dr
Phone
0114 226 5068
Email
s.danson@sheffield.ac.uk
First Name & Middle Initial & Last Name & Degree
Sarah Danson, Dr
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juliet Gray, Prof
Phone
0238 120 6639
Email
Juliet.Gray@uhs.nhs.uk
First Name & Middle Initial & Last Name & Degree
Juliet Gray, Prof
Facility Name
Clatterbridge Cancer Centre
City
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dan Palmer, Dr
Phone
0151 706 4172 / 0151 706 4177
Email
daniel.palmer@liverpool.ac.uk
First Name & Middle Initial & Last Name & Degree
Dan Palmer, Dr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.
IPD Sharing Time Frame
All requests for data relating to this treatment arm that are made within 5 years from last patient last visit for the atezolizumab treatment arm will be considered; requests made subsequently will be considered where possible.
IPD Sharing Access Criteria
When a request has been approved, Cancer Research UK will provide access to the de-identified individual patient-level data and appropriate supporting information. A signed Data Sharing Agreement must be in place before accessing requested information. Requests should be submitted to drugdev@cancer.org.uk
Links:
URL
http://CRUK.org/determine
Description
Overview of the DETERMINE trial.
URL
https://clinicaltrials.gov/ct2/show/NCT05722886
Description
ClinicalTrials.gov record for DETERMINE Trial Master Screening Protocol (NCT05722886).

Learn more about this trial

DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Teenage/Young Adults and Paediatric Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition

We'll reach out to this number within 24 hrs