BridgeMD
A MULTICENTER, SINGLE-ARM, THREE COHORT, PHASE II TRIAL OF PATRITUMAB DERUXTECAN (HER3-DXD) IN PATIENTS WITH ACTIVE BRAIN METASTASES FROM HER3-EXPRESSING ADVANCED BREAST CANCER AND NON–SMALL CELL LUNG CANCER, AND IN PATIENTS WITH LEPTOMENINGEAL CARCINOMATOSIS FROM HER3-EXPRESSING ADVANCED SOLID TUMORS (The TUXEDO-3 Study)
EU CTIS ID: 2023-503251-10-00
What this study is testing
Cohorts 1 and 2: To assess the intracranial objective response rate (ORR-IC) per local investigator as judged by best CNS response according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of HER3-DXd in patients with active brain metastases from MBC and aNSCLC. Cohort 3: To analyze the overall survival (OS) rate at 3 months of HER3-DXd in patients with advanced solid tumors with untreated LMD.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
- Patient has adequate bone marrow, liver, and renal function: Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 based on Cockcroft−Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.
- Participants in cohort 1 and cohort 2 must have received at least one prior line of systemic treatment in the advanced setting. Note I: prior systemic treatments for BC eligible patients would be defined as follows: TNBC patients must have received at least one line of prior systemic therapy for advanced disease. Luminal BC patients must have received at least one line of ET and one line of CT in the advanced setting. HER2[+] BC patients must have progressed on at least two previous treatments with HER2-targeted therapies in the advanced setting. Note II: prior systemic treatments for aNSCLC eligible patients would be defined as follows: Patients without activating driver alterations must have received at least one prior line of standard of care systemic therapy for locally advanced or metastatic disease. Patients with activating driver alterations must have received at least one prior line of an approved genotype-directed therapy. Participants with EGFR T790M mutation who received first-line treatment with erlotinib, gefitinib, afatinib, or dacomitinib must have received second-line treatment with osimertinib and have documentation of radiological disease progression.
- Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0). Note: Except for alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion.
- For women of childbearing potential: agreement to remain abstinent (must refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the CSP, during the treatment period and for at least 7 months after the last dose of study treatment, whichever is longer. Women of childbearing potential must have a negative serum pregnancy test within 14 days before study treatment initiation (with result available prior to dosing) and must agree to refrain from donating eggs during the entire study treatment period and for 7 months after the last administration of the study drug.
- Being male subjects, surgically sterile or having agreed with true abstinence (must refrain from heterosexual intercourse), or whose female partners are willing to agree with true abstinence or use barrier contraceptive measures mentioned above during the entire study treatment period and for 4 months after the last administration of the study drug. Males must agree to refrain from donating sperm during the entire study treatment period and for 4 months after the last administration of the study drug.
You likely can't join if
- Current participation in another therapeutic clinical trial.
- Pregnant or lactating women.
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.
- Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥350, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended.
- History of a major surgical procedure (defined as requiring general anesthesia) or significant traumatic injury within 21 days prior to randomization, or patients who have not recovered from the side effects of any major surgery.
See the full eligibility criteria
Who can join
- Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
- Patient has adequate bone marrow, liver, and renal function: Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 based on Cockcroft−Gault glomerular filtration rate estimation for patients with creatinine levels above institutional normal.
- Participants in cohort 1 and cohort 2 must have received at least one prior line of systemic treatment in the advanced setting. Note I: prior systemic treatments for BC eligible patients would be defined as follows: TNBC patients must have received at least one line of prior systemic therapy for advanced disease. Luminal BC patients must have received at least one line of ET and one line of CT in the advanced setting. HER2[+] BC patients must have progressed on at least two previous treatments with HER2-targeted therapies in the advanced setting. Note II: prior systemic treatments for aNSCLC eligible patients would be defined as follows: Patients without activating driver alterations must have received at least one prior line of standard of care systemic therapy for locally advanced or metastatic disease. Patients with activating driver alterations must have received at least one prior line of an approved genotype-directed therapy. Participants with EGFR T790M mutation who received first-line treatment with erlotinib, gefitinib, afatinib, or dacomitinib must have received second-line treatment with osimertinib and have documentation of radiological disease progression.
- Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0). Note: Except for alopecia or other toxicities not considered a safety risk for the patient at investigator’s discretion.
- For women of childbearing potential: agreement to remain abstinent (must refrain from heterosexual intercourse) or use highly effective contraceptive methods, or two effective contraceptive methods, as defined in the CSP, during the treatment period and for at least 7 months after the last dose of study treatment, whichever is longer. Women of childbearing potential must have a negative serum pregnancy test within 14 days before study treatment initiation (with result available prior to dosing) and must agree to refrain from donating eggs during the entire study treatment period and for 7 months after the last administration of the study drug.
- Being male subjects, surgically sterile or having agreed with true abstinence (must refrain from heterosexual intercourse), or whose female partners are willing to agree with true abstinence or use barrier contraceptive measures mentioned above during the entire study treatment period and for 4 months after the last administration of the study drug. Males must agree to refrain from donating sperm during the entire study treatment period and for 4 months after the last administration of the study drug.
- Patient must be accessible for treatment and follow-up.
- Cohort 1 and cohort 2 specific inclusion criteria: Histologically documented BC (cohort 1) or NSCLC of squamous or non-squamous histologic types (cohort 2).
- Cohort 1 and cohort 2 specific inclusion criteria: Newly diagnosed BM or BM progressing after local treatment.
- Cohort 1 and cohort 2 specific inclusion criteria: Measurable disease according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria, with at least one measurable brain lesion of ≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging (MRI).
- Cohort 1 specific inclusion criterion: Known HER2 status, by local assessment.
- Age ≥ 18 years at time of signing ICF.
- Cohort 3 specific inclusion criteria: Histologically documented solid tumor of any type.
- Cohort 3 specific inclusion criteria: Type I LMD, defined by positive cerebrospinal fluid (CSF) cytology or leptomeningeal biopsy, or type II LMD, defined by clinical findings and neuroimaging only, according to European Society for Molecular Oncology (ESMO) Standard Operating Procedures (SOPs) for Clinical Practice Guideline (CPG) 2017.
- Cohort 3 specific inclusion criteria: Newly diagnosed LMD or LMD progressing after radiotherapy.
- Life expectancy ≥ 6 weeks.
- Karnofsky Performance Status (KPS) ≥70%, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Patient must be able to tolerate therapy.
- Availability and willingness to provide the most recently available tumor tissue sample (formalin-fixed and paraffin-embedded [FFPE], no cytology/cell block, no bone/decalcified bone sample) of primary tumor or any metastatic site from biopsy preferably collected after last round of prior treatment and ≤ 6 months prior to HER3-DXd treatment, if possible, at the time of inclusion for retrospective exploratory biomarker testing. If archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required prior to start of study treatment (unless not possible because of inaccessible tumor location or safety concerns).
- No indication for immediate local therapy (neurosurgery, brain radiotherapy).
- Patient has adequate bone marrow, liver, and renal function: Hematological (without platelet, red blood cell transfusion, and/or granulocyte colony-stimulating factor support within 7 days before first study treatment dose): White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 10.0 g/dL (≥ 6.2 mmol/L).
- Patient has adequate bone marrow, liver, and renal function: Hepatic: Serum albumin ≥ 2.5 g/dL; total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 3 in patients with liver metastases or know history of Gilbert’s disease); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN (≤ 5 in patients with liver metastases); international normalized ratio (INR) < 1.5.
What rules you out
- Current participation in another therapeutic clinical trial.
- Pregnant or lactating women.
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study.
- Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥350, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen). If an HIV infection meets the above criteria, monitoring of viral RNA load and CD4+ count is recommended.
- History of a major surgical procedure (defined as requiring general anesthesia) or significant traumatic injury within 21 days prior to randomization, or patients who have not recovered from the side effects of any major surgery.
- A history of uncontrolled seizures, CNS disorders or serious and/or unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs or interfering with subject safety.
- Patients requiring concomitant use of chronic systemic (intravenously [IV] or oral) corticosteroids at doses higher than 8 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events (AEs), including immune-related adverse events (irAEs) for patients that received immunotherapy in a previous line; (inhaled steroids or intra articular steroid injections are permitted in this study). Note: The use of stable corticosteroid therapy in patients with BM can be discussed with the Medical Monitor.
- Patients with known substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
- Participants who are unable or unwilling to comply with the requirements of the protocol in the opinion of the investigator.
- Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drug.
- Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
- Previous systemic therapy with any anti-HER3 directed drug.
- Known allergy or hypersensitivity to HER3-DXd or any of the drug components.
- Radiotherapy or limited-field palliative radiotherapy within seven days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
- Patient with an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including any of the following: Unstable angina pectoris or documented myocardial infarction within 6 months prior to study entry. Symptomatic pericarditis. Documented congestive heart failure (CHF) (New York Heart Association [NYHA] Class III-IVI). Left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO). Ventricular arrhythmias except for benign premature ventricular contractions. Other cardiac arrhythmias requiring a pacemaker or not controlled with medication. Long QT syndrome (corrected QT interval by Fredericia (QTcF) interval > 450 ms).
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrolment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), or prior pneumonectomy.
- Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.