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

A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL); Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)
• Intervention / Treatment: Drug: ARV-393; Drug: Glofitamab

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.

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Arvinas Operations, Inc.; Phone Number: 475-345-0791; Email: clinicaltrialsARV-393@arvinas.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Clinical Trial Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Clinical Trial Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Clinical Trial Site
  • Odense C, Denmark, 5000
    • Recruiting
    • Clinical Trial Site
• Spain
  • Barcelona, Spain, 8908
    • Recruiting
    • Clinical Trial Site
  • Madrid, Spain, 28050
    • Recruiting
    • Clinical Trial Site
  • Salamanca, Spain, 37007
    • Recruiting
    • Clinical Trial Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Clinical Trial Site
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinical Trial Site
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Clinical Trial Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Clinical Trial Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 10065
      • Recruiting
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Clinical Trial Site
    • New York, New York, United States, 10016
      • Recruiting
      • Clinical Trial Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Recruiting
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Clinical Trial Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Monotherapy Dose escalation; Participants with R/R NHL will receive ARV-393 dose escalation beginning at dose level 1	Drug: ARV-393; Oral daily dose of ARV-393 at a specified dose level
Experimental: Part B Monotherapy: Dose expansion/optimization; 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; Oral daily dose of ARV-393 at a specified dose level
Experimental: Part C Combination therapy: Dose escalation; 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; Oral daily dose of ARV-393 at a specified dose level; Drug: Glofitamab; Glofitamab infusion per labelled prescribing information
Experimental: Part D Combination therapy: Dose expansion/optimization; 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; Oral daily dose of ARV-393 at a specified dose level; Drug: Glofitamab; Glofitamab infusion per labelled prescribing information

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393	Assessment of pharmacokinetic parameter AUC	4 months from first drug dosing
Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393	Assessment of pharmacokinetic parameter AUC	Time Frame: 4 months from first drug dosing
Maximum Concentration (Cmax) for ARV-393	Cmax is an assessment of pharmacokinetic parameter	4 months from first drug dosing
Minimum Concentration (Cmin) for ARV-393	Cmin is an assessment of pharmacokinetic parameter	4 months from first drug dosing
Time to Maximum Concentration (Tmax) for ARV-393	Tmax is an assessment of pharmacokinetic parameter	4 months from first drug dosing
Oral Clearance (CL/F) for ARV-393	CL/F is an assessment of pharmacokinetic parameter	4 months from first drug dosing
Volume of Distribution (Vd/F) for ARV-393	Vd/F is a proportionality factor that relates the amount of drug in the body to the concentration of drug measured in a biological fluid.	4 months from first drug dosing
Overall Response Rate (ORR) Based on Investigator Assessments of Response According to Lugano Response Criteria for NHL and International Primary Central Nervous System Lymphoma (PCNSL) Criteria for Central Nervous System (CNS Lymphoma), if Applicable	ORR is a parameter measuring the anti-tumor activity of the study intervention. It is the percentage of participants reaching a complete response or partial response to the study treatment.	Approximately 2 years
Complete Response Rate (CRR) Based on Investigator Assessments of Response According to the Lugano Response Criteria for NHL and the International PCNSL Criteria for CNS Lymphoma, if Applicable	CRR is a parameter measuring the anti-tumor activity of the study intervention. CRR is percentage of participants with best of response reported as complete response.	Approximately 2 years
Duration of Response (DOR) Based on Investigator Assessments of Response According to the Lugano Response Criteria for NHL and the International PCNSL Criteria for CNS Lymphoma, if Applicable	DOR is the time from the initial response (CR or PR) to the date of progression, or death, whichever occurs first. It is a parameter measuring the anti-tumor activity of the study intervention.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Arvinas Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Lymphadenopathy; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Immunoblastic Lymphadenopathy; glofitamab
• Other Study ID Numbers: ARV-393-101; 2023-510136-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No