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NCT06393738PHASE1Recruiting

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

Arvinas Inc.

Start Date

9/5/2024

Completion Date

3/1/2028

Summary

This clinical trial is studying the safety and potential anti-tumor activity of an investigational drug called ARV-393 in patients diagnosed with advanced Relapsed/Refractory non-Hodgkin's lymphoma (R/R NHL) to determine if ARV-393 may be a possible treatment option. ARV-393 is thought to work by breaking down a protein present in many types of non-Hodgkins lymphomas, which may prevent, slow or stop tumor growth. This is the first time ARV-393 will be used by people. The investigational drug will be given as an oral tablet.

Detailed Description

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

Age Range: 18 years to No maximum

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%.

Interventions

DRUG

ARV-393

DRUG

Glofitamab

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Conditions

Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)

Locations

Clinical Trial Site

New Haven, Connecticut 06510

United States

Clinical Trial Site

Detroit, Michigan 48201

United States

Clinical Trial Site

New Brunswick, New Jersey 10065

United States

Clinical Trial Site

New York, New York 10016

United States

Clinical Trial Site

New York, New York 10021

United States

Clinical Trial Site

Cleveland, Ohio 44122

United States

Clinical Trial Site

Nashville, Tennessee 37203

United States

Clinical Trial Site

Houston, Texas 77030

United States

Clinical Trial Site

Toronto, Ontario M5G 1Z5

Canada

Clinical Trial Site

Montreal, Quebec H3T 1E2

Canada

Clinical Trial Site

Copenhagen, 2100

Denmark

Clinical Trial Site

Odense C, 5000

Denmark

Clinical Trial Site

El Palmar, Murcia 30120

Spain

Clinical Trial Site

Pamplona, Navarre 31008

Spain

Clinical Trial Site

Barcelona, 8908

Spain

Clinical Trial Site

Madrid, 28050

Spain

Clinical Trial Site

Salamanca, 37007

Spain