DETERMINE Trial Treatment Arm 06: Capmatinib in Adult Patients With Cancers Harbouring MET Dysregulations

NCT06988475 | Recruiting Phase 2

• 1 other identifier: CRUKD/21/004 - Treatment Arm 6
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 17

Brief Summary

This clinical trial is looking at a drug called capmatinib. Capmatinib is approved as standard of care treatment for adult patients with certain types of lung cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Capmatinib works in patients with lung cancer with a particular mutation in their cancer known as a METex14 skipping mutation. Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same mutation or other specific mutations or changes which take place in the MET gene. 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.

Conditions

Solid Tumour; Haematological Malignancy; Malignant Neoplasm; Neoplasms by Histologic Type; Neoplasms by Site; Cancer; Malignancy; Glioma; Neuroblastoma; Gastric Cancer; Soft Tissue Sarcoma

Keywords

adult; capmatinib; MET Tyrosine Kinase Receptor; MET exon 14 skipping; MET amplifications; MET fusions; MET activating mutations; MET dysregulations; Antineoplastic Agents; cancer; malignancy; Malignant Neoplasms; Molecular Targeted Therapy; Mutation; Neoplasms by Histologic Type; Neoplasms by Site; Precision Medicine; Protein Kinase Inhibitors; Rare; Tumour-agnostic; METex14 skipping

Outcome Measures

Primary Outcomes (2)

• Objective Response (OR)

  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.

  Disease assessments to be performed up to 24 weeks from the start of trial treatment.

• 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) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response assessment 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.

  Disease assessments to be performed up to 24 weeks from the start of trial treatment.

Secondary Outcomes (11)

• Duration of response (DR)

  Disease assessment performed every 2 cycles of capmatinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of capmatinib for up to 2 years.

• Best percentage change in sum of target lesion / index lesion diameters (PCSD)

  Disease assessment performed every 2 cycles of capmatinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of capmatinib for up to 2 years.

• Time to treatment discontinuation (TTD)

  From first dose of capmatinib to discontinuation of trial treatment up to 5 years with an average calculated and presented with results entry.

• Progression-Free Survival time (PFS)

  Disease assessment performed every 2 cycles of capmatinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of capmatinib for up to 2 years.

• Time to Progression (TTP)

  Disease assessment performed every 2 cycles of capmatinib (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose of capmatinib for up to 2 years.

Study Arms (1)

Treatment Arm 06: Capmatinib

EXPERIMENTAL

This capmatinib treatment arm is for adult partients with cancers harbouring MET dysregulations.

Drug: Capmatinib

Interventions

Capmatinib DRUG

Patients will be administered capmatinib orally at a daily dose of 800 mg consisting of 400 mg (two 200mg 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.

Treatment Arm 06: Capmatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• A. Confirmed diagnosis of a MET-positive malignancy using an analytically next-generation sequencing method (METex14 skipping, MET amplification, MET fusion, or MET activating mutation).
• B. Adult patients ≥18 years old.
• C. Women of childbearing potential are eligible, provided that they meet the following criteria:
• Have a negative serum or urine pregnancy test before enrolment, and
• Agree to use one form of highly effective birth control method (a method that can achieve a failure rate of \<1% when used consistently and correctly), 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 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
• Effective from the first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib.
• D. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from first administration of capmatinib, throughout the trial and for seven days after the last administration of capmatinib:
• Agree to take measures not to father children by using a barrier method of contraception (e.g. condom) or sexual abstinence.

Sponsors & Collaborators

• Cancer Research UK: lead
• University of Birmingham: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Novartis Pharmaceuticals: collaborator
• University of Manchester: collaborator

Study Sites (17)

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

RECRUITING

University Hospital Birmingham

Birmingham, B15 2TT, United Kingdom

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, CB2 OQQ, United Kingdom

NOT YET RECRUITING

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

The Beatson Hospital

Glasgow, G12 OYN, United Kingdom

RECRUITING

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

The Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

RECRUITING

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

Western Park Hospital

Sheffield, S10 2SJ, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Links

• Overview of the DETERMINE trial
• ClinicalTrials.gov record for DETERMINE Trial Master Screening Protocol (NCT05722886).

MeSH Terms

Conditions

Hematologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Neoplasms by Site; Glioma; Neuroblastoma; Stomach Neoplasms; Sarcoma

Interventions

capmatinib

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Connective and Soft Tissue

Study Officials

• Matthew Krebs, Dr

  The Christie Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aida Sarmiento Castro

CONTACT

+44 207 242 0200; determine@cancer.org.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: May 23, 2025
• Study Start: November 19, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: All requests for data relating to this treatment arm that are made within 5 years from last patient last visit for the capmatinib treatment arm will be considered; requests made subsequently will be considered where possible.
• 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.

Locations

GB (17)