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

NCT06393738 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ARV-393-1012023-510136-36-00
• Study Type: interventional
• Target: 255
• Locations: 4 countries
• Sites: 17

Brief 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.

Conditions

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

Keywords

Relapsed/Refractory B cell Non Hodgkin Lymphoma (NHL); Relapsed/Refractory Angioimmunoblastic T-cell lymphoma (AITL); Advanced non-Hodgkin Lymphoma; advanced NHL; relapsed non-Hodgkin Lymphoma; refractory non-Hodgkin Lymphoma; B Cell Advanced Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose Limiting Toxicities During First 28 Days

  Percentage of participants in dose escalation arm at a given dose cohort with AEs meeting protocol defined dose limiting toxicities during cycle 1 (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

  Adverse events as characterized by type, frequency, severity, seriousness, and relationship to study drug

  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

  Shifts in vital signs, ECGs, and laboratory parameters from study baseline

  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

• Percentage of Participants With Grade 3 or Grade 4 Clinical Lab Abnormalities Using the Common Terminology Criteria for Adverse Events (CTCAE) With Scale From Grade 1 Grade 5. Higher Score Means Worse Outcome

  Incidence of Grade 3 and Grade 4 clinical laboratory abnormalities

  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

Secondary Outcomes (10)

• Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393

  4 months from first drug dosing

• Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393

  Time Frame: 4 months from first drug dosing

• Maximum Concentration (Cmax) for ARV-393

  4 months from first drug dosing

• Minimum Concentration (Cmin) for ARV-393

  4 months from first drug dosing

• Time to Maximum Concentration (Tmax) for ARV-393

  4 months from first drug dosing

Study Arms (4)

Part A Monotherapy Dose escalation

EXPERIMENTAL

Participants with R/R NHL will receive ARV-393 dose escalation beginning at dose level 1

Drug: ARV-393

Part B Monotherapy: Dose expansion/optimization

EXPERIMENTAL

Dose expansion and optimization of ARV-393 will be conducted in Part B to determine the recommended phase 2 dose (RP2D) for participants with R/R NHL

Drug: ARV-393

Part C Combination therapy: Dose escalation

EXPERIMENTAL

Participants with R/R diffuse large B-cell lymphoma (DLBCL) will receive ARV-393 in combination with glofitamab, beginning at an ARV-393 dose informed by the Part A. Glofitamab will be given per labelled prescribing information. Part C will be conducted in non-USA centers.

Drug: ARV-393; Drug: Glofitamab

Part D Combination therapy: Dose expansion/optimization

EXPERIMENTAL

Part D will be an optimization of ARV-393 in combination with glofitamab to determine a potential RP2D for ARV-393 in the combination regimen. Part D will be conducted in non-USA centers in participants with R/R DLBCL.

Drug: ARV-393; Drug: Glofitamab

Interventions

ARV-393 DRUG

Oral daily dose of ARV-393 at a specified dose level

Part A Monotherapy Dose escalation; Part B Monotherapy: Dose expansion/optimization; Part C Combination therapy: Dose escalation; Part D Combination therapy: Dose expansion/optimization

Glofitamab DRUG

Glofitamab infusion per labelled prescribing information

Part C Combination therapy: Dose escalation; Part D Combination therapy: Dose expansion/optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Arvinas Inc.: lead

Study Sites (17)

Clinical Trial Site

New Haven, Connecticut, 06510, United States

RECRUITING

Clinical Trial Site

Detroit, Michigan, 48201, United States

RECRUITING

Clinical Trial Site

New Brunswick, New Jersey, 10065, United States

RECRUITING

Clinical Trial Site

New York, New York, 10016, United States

RECRUITING

Clinical Trial Site

New York, New York, 10021, United States

RECRUITING

Clinical Trial Site

Cleveland, Ohio, 44122, United States

RECRUITING

Clinical Trial Site

Nashville, Tennessee, 37203, United States

RECRUITING

Clinical Trial Site

Houston, Texas, 77030, United States

RECRUITING

Clinical Trial Site

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Clinical Trial Site

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Clinical Trial Site

Copenhagen, 2100, Denmark

RECRUITING

Clinical Trial Site

Odense C, 5000, Denmark

RECRUITING

Clinical Trial Site

El Palmar, Murcia, 30120, Spain

RECRUITING

Clinical Trial Site

Pamplona, Navarre, 31008, Spain

RECRUITING

Clinical Trial Site

Barcelona, 8908, Spain

RECRUITING

Clinical Trial Site

Madrid, 28050, Spain

RECRUITING

Clinical Trial Site

Salamanca, 37007, Spain

RECRUITING

MeSH Terms

Conditions

Recurrence; Immunoblastic Lymphadenopathy; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Interventions

glofitamab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphadenopathy; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Central Study Contacts

Arvinas Operations, Inc.

CONTACT

475-345-0791; clinicaltrialsARV-393@arvinas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 1, 2024
• Study Start: September 5, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); CA (2); DK (2); ES (5)