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Combination of trastuzumab and pertuzumab for treating cancers with HER2 mutations

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 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations.

Phase2; Phase3 Interventional Cancer Research UK · NCT05786716

This study is testing if a combination of two cancer drugs, trastuzumab and pertuzumab, can help adults and young people with cancers that have HER2 mutations or amplifications.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment30 (estimated)
Ages12 Years and up
SexAll
SponsorCancer Research UK Academic / other
Drugs / interventionsTRASTUZUMAB, PERTUZUMAB
Locations27 sites (Belfast and 26 other locations)
Trial IDNCT05786716 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of trastuzumab and pertuzumab, two monoclonal antibodies, in treating various cancers that exhibit HER2 amplification or activating mutations. The study aims to include adult, pediatric, and teenage/young adult patients with both rare and common cancers where these HER2 alterations are present. Participants will receive the drug combination until disease progression or unacceptable toxicity occurs, with follow-up assessments conducted for two years post-treatment. The ultimate goal is to potentially provide new treatment options for patients through the NHS and Cancer Drugs Fund if the results are positive.

Who should consider this trial

Good fit: Ideal candidates include patients aged 12 years and older with confirmed HER2 amplification or activating mutations in their malignancies.

Not a fit: Patients without HER2 amplification or activating mutations, or those with malignancies not included in the study criteria, may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could offer new therapeutic options for patients with cancers that currently have limited treatment alternatives.

How similar studies have performed: Other studies have shown success with trastuzumab and pertuzumab in breast cancer, but this application to other cancer types is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 04 (TRASTUZUMAB AND PERTUZUMAB) OUTLINED BELOW\*

\*When trastuzumab- and pertuzumab-specific inclusion/exclusion criteria or precautions below differ from those specified in the Master Protocol, the trastuzumab- and pertuzumab-specific criteria will take precedence.

Inclusion Criteria:

A. Confirmed diagnosis of a malignancy harbouring HER2 amplification, or an appropriate activating mutation as defined by the MTB, using an analytically validated next-generation sequencing method.

• A HER2 amplification copy number between 5-9 will require an MTB discussion. A HER2 amplification copy number ≥10 will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities (such as multiple gene amplifications) that require MTB discussion.

B. Age 12 years or above.

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 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 trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later).

D. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later):

* Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to 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 C, above.
* 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.

E. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken.

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

G. PAEDIATRIC PATIENTS (\<18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.

Exclusion Criteria:

A. Diagnosis of HER2-positive early or metastatic breast cancer.

B. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within seven months following their last dose of trastuzumab or pertuzumab (whichever is later).

C. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

D. Known hypersensitivity to trastuzumab or pertuzumab, murine proteins, or to any of the excipients.

E. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during trastuzumab and pertuzumab treatment or within six months after the final dose of trastuzumab and pertuzumab.

F. Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias (within three months), NYHA class III or IV congestive heart failure.

Left Ventricular Ejection Fraction \<55%.

Patients with a cerebrovascular event (including stroke or transient ischaemic attack \[TIA\]) or cardiovascular event (including acute myocardial infarction \[MI\]) within three months before the first dose of trastuzumab and pertuzumab.

• Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of trastuzumab and pertuzumab, and patients with punctate CNS haemorrhages \<3 mm may be considered.

G. Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to trastuzumab or pertuzumab.

H. 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.

I. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of trastuzumab and pertuzumab, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:

* CD4 count ≥350/μL;
* undetectable viral load;
* receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and
* no HIV/ acquired immune deficiency syndrome (AIDS)-associated opportunistic infection in the last 12 months.

Where this trial is running

Belfast and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
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Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.