A Phase 2/3 interventional study of Alectinib and Atezolizumab in Haematological Malignancy and Solid Tumour, sponsored by Cancer Research UK. Recruiting at 27 sites in United Kingdom. Per ClinicalTrials.gov, last updated 2026-07-01.
Sponsored by Cancer Research UK · Phase 2/3, Interventional, and Treatment
DETERMINE is an open-label phase II/III trial. It will look at targeted treatments in rare cancers or common cancers with rare genetic change (mutation). Patients must have a cancer with an identified mutation. This could be found during routine testing or as part of another research programme. The DETERMINE trial will recruit adults, teenagers and children. If a drug is found to benefit a new patient group, the study team will work with the NHS and the Cancer Drugs Funds to see if these drugs can be available for patients in the future. This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), additional records will be added to clinicaltrials.gov for each treatment arm.
DETERMINE is an umbrella-basket platform trial to evaluate the efficacy of licensed targeted therapies in rare* adult, paediatric and teenage/young adult (TYA) cancers with actionable genomic alterations, including common cancers with rare actionable alterations.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and TYA cancers) or common cancers with rare alterations.
The number of treatment arms opened will depend on the number of licensed medicines identified for inclusion. Each trial cohort has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each.
This clinicaltrials.gov record refers to the Overall Trial Protocol (Master Screening Record), please refer to the references section for links to the individual treatment arm records.
The main aims of the clinical trial arms are:
This Master Screening Record will capture the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm. The trial results (according to the protocol defined outcome measures) will be reported per-arm for each treatment arm.
The ultimate aim is to translate positive clinical findings to the NHS to provide new treatment options for rare adult, paediatric and TYA cancers.
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED.
Core Inclusion Criteria:
Any patient (adult patients or children and TYA as defined in each treatment arm appendix) with histologically proven locally advanced or metastatic cancer (solid tumour or haematological malignancy) who has:
Women of childbearing potential are eligible provided that they meet the following criteria:
Core exclusion criteria:
Is (or plans to be) a patient in another interventional clinical trial, whilst taking part in this trial. Participation in an observational trial which does not involve administration of an Investigational Medicinal Product (IMP) and which, in the opinion of the local Investigator, would not place an unacceptable burden on the patient would be acceptable e.g. sample collection* or QoL studies.
*for paediatric patients participating in other studies involving tissue/circulating tumour (ct) DNA/other blood collection, consideration would need to be given to the total blood volumes collected (as per the European Medicines Agency blood volume limits for children).
This alectinib treatment arm is for adult, paediatric and TYA patients with ALK-positive cancers.
Drug: Alectinib
This atezolizumab treatment arm is for adult, paediatric and TYA patients with cancers with high tumour mutational burden (TMB) or microsatellite instability high (MSI-high) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD).
Drug: Atezolizumab
This entrectinib treatment arm is for adult, paediatric and TYA patients with ROS1 gene fusion-positive cancers.
Drug: Entrectinib
This trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations.
Drug: Trastuzumab in combination with pertuzumab
This vemurafenib and cobimetinib treatment arm is for BRAF V600 mutation-positive cancers occurring in adults only.
Drug: Vemurafenib in combination with cobimetinib
This capmatinib treatment arm is for adult patients with cancers harbouring MET dysregulations.
Drug: Capmatinib
This dabrafenib and trametinib treatment arm is for adult, paediatric and TYA patients with cancers harbouring BRAF V600 mutations.
Drug: Dabrafenib in combination with trametinib
Adult patients will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Paediatric patients with a body weight ≥40 kg and who are able to swallow the capsules will be administered alectinib orally at a dose of 600 mg (four 150 mg capsules) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Alecensa
Adult patients will receive 1200 mg of atezolizumab intravenously every 21 days. Paediatric patients will receive atezolizumab at a dose of 15 mg/kg (maximum 1200 mg) every 21 days. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Tecentriq
Adult and paediatric patients with body surface area (BSA) ≥1.51 m\^2 will receive entrectinib orally at a dose of 600 mg daily dose (three 200 mg capsules per day). Paediatric patients with BSA \<1.51 m\^2 will receive a dose adjusted for BSA. Each cycle of treatment will consist of 28 days and patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Rozlytrek
The initial loading dose of trastuzumab is 8 mg/kg body weight followed thereafter by a maintenance dose of 6 mg/kg body weight administered intravenously every 21 days. The initial loading dose of pertuzumab is 840 mg followed thereafter by a maintenance dose of 420 mg administered intravenously every 21 days. Paediatric patients will receive a dose of pertuzumab adjusted by body weight. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Herceptin in combination with Perjeta
Patients will receive vemurafenib at a dose of 960 mg (four tablets of 240 mg) orally on a twice daily schedule throughout a 28-day cycle. Patients will receive cobimetinib at a dose of 60 mg (three tablets of 20 mg) to be taken orally, once daily for 21 consecutive days (days 1 to 21 in each 28-day cycle); followed by a 7-day break. Patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Zelboraf in combination with Cotellic
Patients will receive capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200 mg tablets) twice daily. Each cycle of treatment will consist of 28 days and patients may continue on treatment until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Tabrecta
Adult patients (≥18 years) will receive dabrafenib at a dose of 150 mg (two 75 mg tablets) twice daily (total daily dose 300 mg). Paediatric patients (1 to \<12 years) will receive dabrafenib dose adjusted by body weight as 10 mg dispersible tablets orally twice daily. Paediatric patients (≥12 years) and TYA patients (16 to \<18 years) will have the option to receive adult or paediatric dosing. Adult patients will receive trametinib at a daily dose of 2 mg (one 2 mg tablet) orally once daily (total daily dose 2 mg). Paediatric patients receive trametinib at a dose adjusted by body weight as 0.05 mg/m\^2 powder for oral solution twice daily. Paediatric patients (≥12 years) and TYA patients (16 to \<18 years) will have the option to receive adult or paediatric dosing. Each cycle of treatment will consist of 28 days. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Also known as: Tafinlar in combination with Mekinist, Finlee in combination with Spexotras
Number of patients who consent to each arm.
This is a master screening entry with sub-study entries to capture the results of each arm. As such a primary outcome measure for this entry is not relevant, however this entry will be used to report the number of patients with a cancer containing the appropriate genetic alteration that have been successfully allocated and consented to each arm.
Time frame: Up to 5 years.
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Icf
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