BridgeMD
New treatment option for Advanced Malignant Solid Neoplasm
Official title Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)
ClinicalTrials.gov ID: NCT06311214
What this study is testing
What is Enfortumab Vedotin?
Enfortumab Vedotin is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for advanced malignant solid neoplasm.
Also referred to as AGS 22ME, AGS-22M6E.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This phase II ADC MATCH screening and multi-sub-study treatment trial is evaluating whether biomarker-directed treatment with one of three antibody-drug conjugates (ADCs) (sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan) works in treating patients with solid tumor cancers that have high expression of the Trop-2, nectin-4, or HER2 proteins and that may have spread from where they first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or to other places in the body (metastatic). Precision medicine is a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, or treat disease in a way that is tailored to the patient.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- SCREENING PROTOCOL
- Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:
- Patients must have disease not amenable to curative-intent therapy AND
- Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are...
- Patients with disease for which no standard treatment exists that has been shown to confer benefit OR
You likely can't join if
- SCREENING PROTOCOL EXCLUSION CRITERIA:
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are...
- Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \> 2), (2) any...
- History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
- Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of...
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
See the full eligibility criteria
Who can join
- SCREENING PROTOCOL
- Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:
- Patients must have disease not amenable to curative-intent therapy AND
- Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are intolerant to such treatment will be eligible, if other eligibility...
- Patients with disease for which no standard treatment exists that has been shown to confer benefit OR
- Patients who are willing to forego standard therapies known to confer benefit
- NOTE: Patients can be on therapy at the time of initiating the Screening Protocol if the patient is interested in treatment on ADC MATCH upon progression, and the physician deems this appropriate
- Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment or must submit archival tissue to determine RNA overexpression of ADC TOIs by the TARGET Assay. Patients who have high...
- Patients must be willing to undergo mandatory pre-treatment and on-treatment tumor biopsies. Patients who do not consent to these research biopsies will not be eligible for prescreening. Patients who have screened and...
- Patients must have measurable disease. (Per radiologic imaging within the past 2 months).
- Note: Patients with active metastatic disease that is not measurable but who are expected to be eligible for a Treatment Cohort can be screened after discussion with the primary investigator (PI)
- Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of the Cancer Therapy Evaluation Program (CTEP) investigational new drug (IND) agents to be used in the study in patients...
- Eastern Cooperative Oncology Group performance status of 0-2 based on most recent assessment (Karnofsky ≥ 50%)
- No history of transfusion dependence
- No history of persistent bone marrow suppression (absolute neutrophil count ≥ 1,500/mL and platelets ≥ 100,000/mL not attributable to active therapy; patients currently on bone marrow suppressive therapy can undergo...
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × ULN (New testing will not be performed for the screening protocol, but rather existing...
- Aspartate transaminase (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 × institutional ULN. Transaminases up to 5 × ULN in the presence of liver...
- Creatinine ≤ institutional ULN OR glomerular filtration rate ≥ 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal unless data exists supporting safe use at lower kidney function values...
- Patients must have albumin ≥ 3 g/dL
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational agents are eligible for...
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association...
- Women of childbearing potential must not be known to be pregnant. Pregnancy testing is not required
- Ability to understand and the willingness to sign a written informed consent document
- ADDITIONAL FOR TREATMENT COHORTS:
- Women of childbearing potential must have a negative serum pregnancy test result at treatment cohort screening
- The effects of the study drugs on the developing human fetus are unknown. For this reason and because investigational agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of...
- Hemoglobin \> 9.0 g/dL
- Leukocytes ≥ 3000/mL
- Absolute neutrophil count ≥ 1,500/mL
- Platelets ≥ 100,000/mL
- Patient must be willing to sign the relevant treatment cohort consent form
- Patients should have received no more than 3 prior lines of chemotherapy in the advanced/metastatic setting. Therapy given for only 1 cycle and discontinued because of toxicity in the absence of disease progression will...
- Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- COHORT A
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort A registration
- Patient must have high Trop-2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
- Patients who have Trop-2 IHC testing without RNA testing or who have Trop-2 IHC 2 or 3+ expression but do not have Trop-2 expression detected on RNA testing will not be eligible for the trial.
- Patients who have Trop-2 RNA expression and Trop-2 IHC 2+ or 3+ on another Trop-2 IHC test will undergo Trop-2 testing with the integral MDACC IHC assay
- Patients who already have RNA expression testing demonstrating Trop-2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision...
- COHORT B
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort B registration
- Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
- COHORT C
- Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort C registration
- Patient must have HER2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center (MDACC) IHC assay
- Patients who have HER2 IHC testing without RNA testing or who have HER2 IHC 2 or 3+ expression but do not have HER2 expression detected on RNA testing will not be eligible for the trial
- Patients who have HER2 RNA expression and HER2 IHC 3+ or 2+ on another HER2 IHC test will undergo HER2 testing with the integral MDACC IHC assay
- Patients who already have RNA expression testing demonstrating HER2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology...
- Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after...
- LVEF ≥50% within 28 days before enrollment
What rules you out
- SCREENING PROTOCOL EXCLUSION CRITERIA:
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after central nervous...
- Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \> 2), (2) any history of unstable angina, (3) myocardial infraction within the past...
- History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
- Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and/or active ocular...
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
- History of interstitial lung disease or pneumonitis requiring steroid therapy
- Grade 2 or greater peripheral neuropathy
- Patients requiring the use of full dose coumarin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted
- Note: Warfarin may not be started while enrolled in the treatment cohorts. Stopping the anticoagulation for biopsy should be per site standard operating practice
- Pregnant women are excluded from the study because the study drugs are investigational or approved agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for...
- ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:
- Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 2 weeks or 5 half-lives (whichever is shorter) from any...
- Patients who are currently receiving any other investigational agent(s)
- Received systemic therapy with corticosteroids at \> 20 mg/day prednisone or equivalent within 1 week prior to cycle 1 day 1
- Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- When the corrected QT interval (QTc) by Fridericia's formula is \ 450 ms in males and \> 470 ms in females. When the QTc by Rautaharju's formula is ≥ 120 ms, \> 450 ms in males and \> 470 ms in females
- Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal use
- Received a live, attenuated vaccine within 30 days prior to cycle 1 day 1. Enrolled patients should not receive live vaccine during the study. Non-live COVID vaccines will be allowed on study, but it is recommended to...
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric...
- Other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
- COHORT A EXCLUSION CRITERIA:
- Patients with histologically documented advanced colorectal cancer, urothelial cancer, head and neck cancer (Note: exceptions include patients with adenoid cystic cancer, salivary gland cancer, thyroid cancer, and...
- Note: Patients with cancer of unknown primary are allowed
- Patients who have received growth factor support within 2 weeks of study treatment initiation
- Coadministration of sacituzumab govitecan-hziy(IMMU-132) with inhibitors of UGT1A1 may increase systemic exposure to the active metabolite, SN-38. UGT1A1 inhibitors should not be administered concomitantly with...
- Prior topoisomerase 1 inhibitor treatment
- Prior treatment with a Trop-2-targeting ADC
- Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of treatment cohort A registration
- COHORT B EXCLUSION CRITERIA:
- Patients with histologically documented advanced urothelial cancer, head and neck cancer (to include salivary gland cancer and adenoid cystic cancer), breast cancer, lung cancer, gastric cancer, gastroesophageal...
- Note: Patients with cancer of unknown primary are allowed
- Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4. Washout period is 2 weeks prior to study treatment initiation
- History of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes mellitus is defined as hemoglobin A1c ≥ 8% or hemoglobin A1c between 7 and \< 8% with associated...
- Known active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated
- Known hypersensitivity to enfortumab vedotin or to any excipient in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20), or known hypersensitivity to...
- Prior treatment with an ADC with vedotin payload
- COHORT C EXCLUSION CRITERIA:
- Patients with histologically documented advanced breast cancer, non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), gastric cancer, or gastroesophageal junction (GEJ) cancer
- Note: Patients with cancer of unknown primary are allowed
- Previous treatment with topoisomerase I inhibitors as a free form or as other formulations
- Prior
The study team makes the final eligibility decision.
Where it's taking place
- Duarte, California, United States
- Encinitas, California, United States
- Irvine, California, United States
- La Jolla, California, United States
- San Diego, California, United States
- New Haven, Connecticut, United States
- Trumbull, Connecticut, United States
- Gainesville, Florida, United States
- Chicago, Illinois, United States
- Lexington, Kentucky, United States
- New Orleans, Louisiana, United States
- Boston, Massachusetts, United States
- City of Saint Peters, Missouri, United States
- Creve Coeur, Missouri, United States
- St Louis, Missouri, United States
- New York, New York, United States
- Columbus, Ohio, United States
- Oklahoma City, Oklahoma, United States
- Nashville, Tennessee, United States
- Houston, Texas, United States
+ 3 more site(s).
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 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Duarte, California, United States; Encinitas, California, United States; Irvine, California, United States; La Jolla, California, United States; San Diego, California, United States; New Haven, Connecticut, United States and 17 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.