What side effects are associated with this type of intervention?

Common treatments for brain metastases, including HER3-directed antibody-drug conjugates like Patritumab Deruxtecan, often have side effects such as neutropenia, anemia, thrombocytopenia, and interstitial lung disease or pneumonitis. Other systemic therapies for brain metastases, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, can cause fatigue, diarrhea, rash, and liver enzyme abnormalities. Additionally, treatments targeting the VEGF pathway may lead to neurovascular events like ischemic or hemorrhagic strokes, transient ischemic attacks, and posterior reversible encephalopathy syndrome.

What prior FDA approvals exist?

FDA approvals for the treatment of brain metastases have included several next-generation tyrosine kinase inhibitors and immune checkpoint inhibitors, particularly for tumors like NSCLC, melanoma, and breast cancer. While specific approvals for HER3-directed antibody-drug conjugates like Patritumab Deruxtecan are not detailed, similar drugs such as fam-trastuzumab deruxtecan (a HER2-directed antibody-drug conjugate) have shown efficacy in metastatic settings, including brain metastases. These treatments aim to prolong survival and improve quality of life by targeting specific molecular pathways involved in cancer progression.

What other types of research exist?

Promising alternatives to Patritumab Deruxtecan for brain metastases patients include entrectinib and repotrectinib. Entrectinib has shown efficacy in NTRK fusion-positive cancers with CNS penetration, while repotrectinib has demonstrated potent antitumor activity and efficient CNS penetration in ROS1-rearranged non-small cell lung cancer.

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Monoclonal Antibodies

Patritumab Deruxtecan for Brain Tumor (PARAMETer Trial)

Phase 2

Waitlist Available

Research Sponsored by Mustafa Khasraw, MBChB, MD, FRCP, FRACP

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 40 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if a targeted cancer drug called patritumab deruxtecan can reach brain tumors in patients whose cancer has spread to the brain. The drug works by using an antibody to deliver chemotherapy directly to the cancer cells. Patients will receive the drug before surgery to see how well it works and if it is safe.

Who is the study for?

This trial is for adults with new or returning brain tumors that can be removed by surgery. They should have minimal symptoms, agree to a craniotomy, and use birth control if needed. Eligible cancers include melanoma, stomach, breast, colorectal, bladder, ovarian cancer etc., with good performance status and organ function.

What is being tested?

The study tests patritumab deruxtecan (HER3-DXd) in patients before they undergo brain tumor removal surgery. It aims to see if the drug reaches the brain tissue after one dose.

What are the potential side effects?

Potential side effects of patritumab deruxtecan may include reactions related to drug infusion, issues affecting organs like lungs or liver due to pre-existing conditions or allergies specific to this medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 40 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~40 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 40 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Brain

Secondary study objectives

Assess the evidence of tumor cell death via histopathological examination and measurement of γH2AX levels in tumor tissue.

Brain

Craniotomy

Side effects data

From 2023 Phase 1 & 2 trial • 182 Patients • NCT02980341

71%

Nausea

52%

Platelet count decreased

48%

Stomatitis

38%

Decreased appetite

38%

Fatigue

38%

Neutrophil count decreased

33%

White blood cell count decreased

33%

Alanine aminotransferase increased

33%

Vomiting

33%

Diarrhoea

29%

Epistaxis

29%

Aspartate aminotransferase increased

29%

Constipation

29%

Alopecia

24%

Nasopharyngitis

24%

Anaemia

19%

Pyrexia

19%

Hypokalaemia

19%

Neutropenia

19%

Thrombocytopenia

14%

Dizziness

14%

Urinary tract infection

14%

Malaise

14%

Back pain

14%

Rash

14%

Hypocalcaemia

14%

Dry skin

14%

Arthralgia

10%

Hypoalbuminaemia

10%

Delirium

10%

Peripheral sensory neuropathy

10%

Taste disorder

10%

Abdominal pain upper

10%

Abdominal distension

10%

Dyspepsia

10%

Abdominal discomfort

10%

Blood alkaline phosphatase increased

10%

Febrile neutropenia

10%

Rash maculo-papular

10%

Myalgia

10%

Abdominal pain

10%

Dyspnoea

10%

Ingrowing nail

10%

Gingival pain

Upper-airway cough syndrome

Oedema peripheral

Dysgeusia

Eczema

Pneumonitis

Arrhythmia

Haemorrhoids

Pruritus

Oedema

Electrocardiogram QT prolonged

Rash pustular

Hepatic function abnormal

Skin hyperpigmentation

Upper respiratory tract infection

Disease progression

Cognitive disorder

Epilepsy

Weight decreased

Leukopenia

Cataract

Pancytopenia

Conjunctivitis

Contusion

Cough

Hyponatraemia

Pneumonia

Palpitations

Extradural haematoma

Dehydration

Gastrooesophageal reflux disease

Hypomagnesaemia

Dysuria

Pneumothorax

Cystitis

Compression fracture

Delirum

Pneumonia aspiration

Headache

Muscular weakness

Dry mouth

Melanocytic naevus

100%

80%

60%

40%

20%

Study treatment Arm

Dose Expansion: HER3-Low 6.4 mg/kg

Dose Finding: 4.2/6.4 mg/kg

Dose Escalation: Cohort 1.6 mg/kg

Dose Escalation/Dose Finding: Cohort 4.8 mg/kg

Dose Escalation/Dose Finding: Cohort 6.4 mg/kg

Dose Expansion: TNBC 6.4 mg/kg

Dose Finding: 3.2/4.8/6.4 mg/kg

Dose Expansion: HER3 High 4.8 mg/kg

Dose Escalation: Cohort 3.2 mg/kg

Dose Escalation: Cohort 8.0 mg/kg

Dose Expansion: HER3-High 6.4 mg/kg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Patritumab deruxtecanExperimental Treatment1 Intervention

15 participants with surgically-resectable brain metastases from multiple solid tumor primary histologies known to express HER3 will be treated. Patritumab deruxtecan (HER3-DXd) will be administered IV 5.6 mg/kg as a single dose 1-3 days prior to planned craniotomy and resection of BrM. Participants will undergo specimen collection prior to and during the planned craniotomy, including tumor, blood, and cerebrospinal fluid (CSF).

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for brain metastases, such as antibody-drug conjugates (ADCs) like Patritumab Deruxtecan, work by combining a monoclonal antibody targeting a specific tumor antigen (e.g., HER3) with a cytotoxic drug. This targeted approach allows for the direct delivery of chemotherapy to cancer cells, reducing harm to healthy cells. Other treatments include tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors, which target specific pathways involved in tumor growth and immune evasion. These targeted therapies are particularly important for brain metastases patients as they offer the potential for more effective and less toxic treatments, addressing the challenges of drug delivery to the brain.

Anti-EGFR VHH-armed death receptor ligand-engineered allogeneic stem cells have therapeutic efficacy in diverse brain metastatic breast cancers.Brain metastases in metastatic cancer: a review of recent advances in systemic therapies.