Trastuzumab Deruxtecan for Brain Cancer

Overseen By Shanu Modi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Heart failure, Lung disease, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out how much tratuzumab deruxtecan (T-DXd) can penetrate the tumor when injected into the body, and whether T-DXd may be an effective treatment for brain cancers that express the HER2 protein.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, there is a mention of an adequate treatment washout period, which suggests you might need to stop certain treatments before joining the study. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Trastuzumab Deruxtecan for brain cancer?

Trastuzumab Deruxtecan has shown effectiveness in treating HER2-positive breast cancer with brain metastases, achieving complete response in some cases and demonstrating the ability to cross the blood-brain barrier, which is crucial for treating brain tumors. ^{1 2 3 4 5}

What safety information is available for Trastuzumab Deruxtecan (Enhertu, DS-8201a)?

Trastuzumab Deruxtecan has been studied for safety in various cancers, showing a generally manageable safety profile. Common side effects include blood and stomach issues, with serious warnings for lung problems and risks to unborn babies. ^{1 6 7 8 9}

What makes the drug Trastuzumab Deruxtecan unique for treating brain cancer?

Trastuzumab Deruxtecan is unique because it is a HER2-targeted antibody-drug conjugate that can cross the blood-tumor barrier, which is a challenge for many treatments, and shows activity on brain metastases. ^{1 2 3 7 9}

Research Team

Nelson Moss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with brain cancer that expresses the HER2 protein, who have a life expectancy of more than 12 weeks and are scheduled for neurosurgical resection/biopsy. Participants must be over 18, not pregnant or breastfeeding, and have recovered from previous treatments. They should not have had a heart attack recently or suffer from significant illnesses that could interfere with the study.

Inclusion Criteria

Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential

My diagnosis is glioblastoma confirmed by a biopsy.

I can care for myself but may need occasional help.

Exclusion Criteria

I have had symptoms of heart failure.

You have had an allergic reaction to T-DXd in the past, or it is not safe for you to take T-DXd.

I have had a lung removed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trastuzumab deruxtecan (T-DXd) to assess tumor penetration and efficacy

Up to 24 months

Surgery

Participants undergo neurosurgical resection/biopsy to evaluate T-DXd penetration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Trastuzumab Deruxtecan

Trial Overview The trial is testing Trastuzumab deruxtecan (T-DXd) to see how well it penetrates brain tumors and if it's effective against certain types of brain cancers related to the HER2 protein. It will involve patients receiving T-DXd injections before their planned surgeries.

Participant Groups

Group I: Cohort C Experimental Treatment 1 Intervention

Participants with recurrent glioblastoma requiring neurosurgical resection/biopsy

Group II: Cohort B Experimental Treatment 1 Intervention

Participants with Her2-expressing or solid tumors with activating ERBB2 mutations with 1 or more CNS metastases requiring neurosurgical resection/biopsy with no prior T-DXd and prior T-DXd exposure and with documented radiological CNS progression while on T-DXd, requiring neurosurgical resection/biopsy of 1 or more recurrent metastases, with continuation of T-DXd until prior to surgery

Group III: Cohort A Experimental Treatment 1 Intervention

Participants with Her2-expressing or solid tumors with activating ERBB2 mutations with 1 or more CNS metastases requiring neurosurgical resection/biopsy with no prior T-DXd

Trastuzumab Deruxtecan is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Approved in United States as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma
• HER2-low breast cancer

Approved in Japan as Enhertu for:

• Unresectable or metastatic HER2-positive breast cancer
• Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Trastuzumab deruxtecan (ENHERTU®) is an innovative treatment that combines an antibody targeting HER2 with a DNA topoisomerase I inhibitor, specifically designed for HER2-expressing solid tumors, including various types of cancer.

It received accelerated approval in the USA based on the promising results from the phase 2 DESTINY-Breast01 trial, which focused on patients with advanced HER2-positive breast cancer who had already undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. Keam, SJ.[2020]

In the TUXEDO-1 trial involving 15 patients with HER2-positive breast cancer and brain metastases, trastuzumab deruxtecan achieved a high overall intracranial response rate of 73.3%, indicating its efficacy in treating this challenging condition.

The treatment was well-tolerated, with no new safety concerns reported, and patients maintained their quality of life and cognitive functioning throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Bartsch, R., Berghoff, AS., Furtner, J., et al.[2022]

Trastuzumab deruxtecan is an innovative HER2-targeted therapy that can effectively penetrate the blood-tumor barrier, making it a promising option for treating brain metastases.

The use of patient-derived xenograft models and early-phase trials is crucial for evaluating the effectiveness of new treatments like trastuzumab deruxtecan in targeting brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Metastasis from HER2-Positive Breast Cancer: An Evolving Landscape. Soffietti, R., Pellerino, A.[2023]

Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in treating HER2+ breast cancer brain metastases, achieving a complete response in a patient with brain-only metastatic disease despite prior heavy treatment.

This case highlights T-DXd's potential to penetrate the blood-brain tumor barrier effectively, warranting further investigation into its use for CNS involvement in HER2+ breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan. Moss, NS., Tosi, U., Santomasso, BD., et al.[2022]

In a phase 2 study involving 184 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a significant response rate of 60.9%, with a median response duration of 14.8 months.

While trastuzumab deruxtecan showed promising efficacy, it was associated with notable adverse effects, including interstitial lung disease in 13.6% of patients, highlighting the need for careful monitoring of pulmonary symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. Modi, S., Saura, C., Yamashita, T., et al.[2021]

Trastuzumab deruxtecan (Enhertu®) has been shown to significantly improve progression-free survival in adults with unresectable or metastatic HER2-positive breast cancer compared to the previous standard treatment, trastuzumab emtansine, in a pivotal phase 3 trial.

The treatment has a generally manageable safety profile, although it is associated with common adverse events like hematological and gastrointestinal disorders, and requires careful monitoring for interstitial lung disease (ILD)/pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. Nie, T., Blair, HA.[2023]

In a phase 1 trial involving 44 patients with HER2-positive gastric or gastro-oesophageal junction cancer, trastuzumab deruxtecan demonstrated a manageable safety profile, with the most common serious side effects being anemia and decreases in blood cell counts, but no drug-related deaths were reported.

The treatment showed promising preliminary activity, with 43.2% of patients achieving a confirmed objective response, indicating its potential effectiveness in patients who had previously been treated with trastuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. Shitara, K., Iwata, H., Takahashi, S., et al.[2020]

Trastuzumab deruxtecan (Enhertu®) has been shown to be significantly more effective than standard chemotherapy in improving overall survival and achieving objective responses in adults with advanced HER2-positive gastric or gastro-oesophageal junction adenocarcinoma, based on results from the phase II DESTINY-Gastric01 trial.

The treatment is generally well-tolerated, with common side effects including nausea and fatigue, but it does carry important safety warnings for interstitial lung disease and embryo-foetal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. Kang, C.[2023]

In a phase 1 trial involving 115 patients with HER2-positive breast cancer previously treated with trastuzumab emtansine, trastuzumab deruxtecan demonstrated a manageable safety profile, with 59.5% of patients achieving a confirmed objective response.

Despite some serious treatment-emergent adverse events, including cases of interstitial lung disease and pneumonitis, the preliminary efficacy results suggest that trastuzumab deruxtecan is a promising treatment option, warranting further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Tamura, K., Tsurutani, J., Takahashi, S., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: First Approval. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Brain Metastasis from HER2-Positive Breast Cancer: An Evolving Landscape. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Unresectable or Metastatic HER2-Positive Breast Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: a dose-expansion, phase 1 study. [2020]

8. France pubmed.ncbi.nlm.nih.gov

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. [2020]