Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)Phase 1NCT06393738
A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.
A Phase 1 study testing ARV-393 and Glofitamab in people with Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL) and Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL), run by Arvinas Inc. at 21 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL), Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)
- What is being tested?
- ARV-393 and Glofitamab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 329 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 5 Sep 2024to Mar 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Current or past history of peripheral eosinophilia, hypereosinophilic syndrome (HES), organ-specific eosinophilic disorder, or drug reaction with eosinophilia and systemic symptoms (DRESS), except for peripheral eosinophilia due to disease under study. Participants with current or prior eosinophilia requiring systemic steroid treatment are excluded regardless of etiology.
- Prior allogeneic stem cell transplant (SCT) or solid organ transplantation.
- Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 60 days prior to Cycle 1 Day 1 (C1D1) or any prior treatment with a BCL6-targeted therapy
- 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;
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- 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%.
Trial locations and contacts
21 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 5 countries
United States10 sites, 9 recruiting
- Recruiting
Clinical Trial Site
Charlottesville, Virginia, 22908
- Recruiting
Clinical Trial Site
Cleveland, Ohio, 44122
- Recruiting
Clinical Trial Site
Detroit, Michigan, 48201
- Recruiting
Clinical Trial Site
Houston, Texas, 77030
- Recruiting
Clinical Trial Site
Miami, Florida, 33136
- Withdrawn
Clinical Trial Site
Nashville, Tennessee, 37203
- Recruiting
Clinical Trial Site
New Brunswick, New Jersey, 10065
- Recruiting
Clinical Trial Site
New Haven, Connecticut, 06510
- Recruiting
Clinical Trial Site
New York, New York, 10016
- Recruiting
Clinical Trial Site
New York, New York, 10021
Spain5 sites, 5 recruiting
- Recruiting
Clinical Trial Site
Barcelona, 8908
- Recruiting
Clinical Trial Site
El Palmar, Murcia, 30120
- Recruiting
Clinical Trial Site
Madrid, 28050
- Recruiting
Clinical Trial Site
Pamplona, Navarre, 31008
- Recruiting
Clinical Trial Site
Salamanca, 37007
Canada3 sites, 3 recruiting
- Recruiting
Clinical Trial SIte
Calgary, Alberta, T2N 5G2
- Recruiting
Clinical Trial Site
Montreal, Quebec, H3T 1E2
- Recruiting
Clinical Trial Site
Toronto, Ontario, M5G 1Z5
Denmark2 sites, 2 recruiting
- Recruiting
Clinical Trial Site
Copenhagen, 2100
- Recruiting
Clinical Trial Site
Odense C, 5000
Australia1 site, 1 recruiting
- Recruiting
Clinical Trial SIte
East Melbourne, Victoria, 3002
About this study
Official title: 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.
Read the 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.
- Conditions
- Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL), Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)
- Being tested
- ARV-393, Glofitamab
- 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
- Medical subject headings
- Recurrence, Immunoblastic Lymphadenopathy, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARV-393Drug
Oral daily dose of ARV-393 at a specified dose level
GlofitamabDrug
Glofitamab infusion per labelled prescribing information
| Study group | Role | What they receive |
|---|---|---|
| Part A Monotherapy Dose escalation | Experimental | Participants with R/R NHL will receive ARV-393 dose escalation beginning at dose level 1 Receives: 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 Receives: 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. Receives: 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. Receives: Drug: ARV-393; Drug: Glofitamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Assessment of pharmacokinetic parameter AUC
Measured: 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
Measured: Time Frame: 4 months from first drug dosing
Maximum Concentration (Cmax) for ARV-393
Cmax is an assessment of pharmacokinetic parameter
Measured: 4 months from first drug dosing
Minimum Concentration (Cmin) for ARV-393
Cmin is an assessment of pharmacokinetic parameter
Measured: 4 months from first drug dosing
Time to Maximum Concentration (Tmax) for ARV-393
Tmax is an assessment of pharmacokinetic parameter
Measured: 4 months from first drug dosing
Oral Clearance (CL/F) for ARV-393
CL/F is an assessment of pharmacokinetic parameter
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2024
- Study start5 Sep 2024
- Primary completionMar 2028 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 329 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arvinas Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06393738
- Sponsor's protocol ID
- ARV-393-101
- Other IDs
- 2023-510136-36-00, 2023
- Status last verified
- Sep 2026
- First submitted
- 25 Apr 2024
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No