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A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.

NCT06393738 · Arvinas Inc.
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Official title
A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma
About this study
This is an open-label, global, multi-center monotherapy and combination dose escalation and dose optimization study to evaluate safety, tolerability and preliminary efficacy of ARV-393. The study will evaluate the safety and tolerability in ascending doses of ARV-393 as monotherapy (A) and in combination with glofitamab (C), as well as determine the RP2D in the dose optimization parts (B for monotherapy) and in combination with glofitamab (D for combination therapy). The monotherapy portions of the study will include participants with R/R NHL. The combination therapy portions of the study with glofitamab will include participants with R/R DLBCL.
Eligibility criteria
Inclusion Criteria: * For Part A and B: Have relapsed/refractory NHL and \>=2 prior systemic therapies, (including rituximab), and be ineligible for known therapies with demonstrated clinical benefit per investigator assessment or, histologically confirmed AITL that has recurred or progressed following institutional standard of care therapy. * For Part C and D: Have R/R DLBCL, not otherwise specified \[NOS (DLBCL, NOS)\] or large B-cell lymphoma (LBCL) arising from follicular lymphoma and have received two or more lines of systemic therapy. * Have at least one bi dimensionally measurable lesion \>1.5-centimeter (cm) in largest dimension for nodal or \>1.0 cm for extranodal lesion. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (NOTE: For Part A only - ECOG PS of 2 is allowed for participants with secondary CNS lymphoma). * Adequate bone marrow function * Adequate kidney function * Adequate Liver Function Exclusion Criteria: * Current or past history of peripheral eosinophilia, hypereosinophilic syndrome (HES), organ-specific eosinophilic disorder, or drug reaction with eosinophilia and systemic symptoms (DRESS). * Prior allogeneic stem cell transplant (SCT) or solid organ transplantation. * Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, melanoma in situ or carcinoma in situ of the breast or cervix, and prostate cancer with active surveillance. * Any of the following in the previous 6 months: * Myocardial infarction, long QT syndrome or family history of long QT syndrome, or Torsade de Pointes; * Clinically important atrial or ventricular arrhythmias; * Serious conduction system abnormalities, 3rd degree atrioventricular (AV block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), New York Heart Association Class III or IV; * Cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinically significant episode of thromboembolic disease; * Active inflammatory gastrointestinal (GI) disease, chronic diarrhea, previous gastric resection, or lap band surgery. * Uncontrolled hypertension despite optimal medical treatment * History of myocarditis. * In ability to comply with listed prohibited treatments. * Standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. * Cardiac ejection fraction \<45%.
Study design
Enrollment target: 255 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-09-05
Estimated completion: 2028-03
Last updated: 2026-02-10
Interventions
Drug: ARV-393Drug: Glofitamab
Primary outcomes
  • Incidence of Dose Limiting Toxicities During First 28 Days (28 days from first study dosing)
  • Percentage of Participants With Adverse Events Characterized by Severity, Seriousness, and Relationship to Study Drug as a Measure of Safety and Tolerability (Parts A and B: From the study baseline to 30 days after last dose of ARV-393; Parts C and D: From the study baseline to 40 days after last dose of ARV-393)
  • Number of Participants With Abnormal Vital Signs, Abnormal ECG Readings (QT Interval) and Abnormal Laboratory Parameters (Parts A and B: From the study baseline to 30 days after last dose of ARV-393; Parts C and D: From the study baseline to 40 days after last dose of ARV-393)
Sponsor
Arvinas Inc. · industry
Contacts & investigators
ContactArvinas Operations, Inc. · contact · clinicaltrialsARV-393@arvinas.com · 475-345-0791
All locations (17)
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New Haven, Connecticut, United States
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Detroit, Michigan, United States
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New Brunswick, New Jersey, United States
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New York, New York, United States
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New York, New York, United States
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Cleveland, Ohio, United States
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Nashville, Tennessee, United States
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Houston, Texas, United States
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Copenhagen, Denmark
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Odense C, Denmark
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El Palmar, Murcia, Spain
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Pamplona, Navarre, Spain
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Barcelona, Spain
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Madrid, Spain
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Salamanca, Spain
A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. · TrialPath