A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.
- Conditions
- Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)
- Interventions
- Registration Number
- NCT06393738
- Lead Sponsor
- Arvinas Inc.
- 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 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, multicenter, phase 1, dose escalation study to evaluate the safety, tolerability and preliminary anti-tumor activity of ARV-393 as a single agent in adult patients with relapsed/refractory non-Hodgkin lymphoma.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 112
- Eligible participants aged ≥18 years.
- Have relapsed/refractory mature B-cell non-Hodgkin lymphoma (NHL) and ≥2 prior systemic therapies, or histologically confirmed AITL that has recurred or progressed following institutional standard-of-care therapy.
- Participants must also have ≥1 measurable lesion at study entry
- Eastern Cooperative Oncology Group performance status of 0 or 1,
- Freshly biopsied or archival tumor tissue available,
- Participants with adequate organ function,
- Participants must accept and follow pregnancy prevention guidance.
- No prior allogeneic stem cell transplant or solid organ transplantation, Autologous stem cell transplant, must not have occurred ≤100 days, previous CAR T-cell therapy ≤60 days, radiotherapy ≤ 2 weeks, systemic anticancer treatment ≤ 5 half-lives or 4 weeks, prior to ARV-393 treatment initiation.
- Participants must not have significant acute or chronic medical illness, including hypereosinophilic syndrome, active interstitial lung disease or pneumonitis, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
- Participants with an inability to comply with listed prohibited treatments.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose escalation ARV-393 Dose escalation will begin at Dose Level 1. Dose escalation or de-escalation decision will be recommended by the cohort review committee.
- Primary Outcome Measures
Name Time Method 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. From the study baseline to at least 30 days after last dose of ARV-393 Incidence of Grade 3 and Grade 4 clinical laboratory abnormalities
Incidence of Dose limiting toxicities during Cycle 1 (28 days) 28 days from first study dosing 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)
Percentage of participants with Adverse Events characterized by severity, seriousness, and relationship to study drug as a measure of safety and tolerability From the study baseline to at least 30 days after last dose of ARV-393 Adverse events as characterized by type, frequency, severity, seriousness, and relationship to study drug
Number of participants with abnormal vital signs, abnormal ECG readings ( QT interval) and abnormal laboratory parameters. From the study baseline to at least 30 days after last dose of ARV-393 Shifts in vital signs, ECGs, and laboratory parameters from study baseline
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) in participants Approximately 2 years ORR is a parameter measuring the anti-tumor activity of ARV-393. it is the percentage of participants reaching a complete response or partial response to the study treatment according to the Lugano response criteria for Non-Hodgkin Lymphoma.
Duration of response (DOR) Approximately 2 years 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 ARV-393
Volume of distribution (Vd/F) for ARV-393 4 months from first drug dosing 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.
Complete response rate (CRR) Approximately 2 years CRR is a parameter measuring the anti-tumor activity of ARV-393. CRR is percentage of participants with best of response reported as complete response according to the Lugano response criteria for Non-Hodgkin Lymphoma
Time to maximum concentration (Tmax) for ARV-393 4 months from first drug dosing Tmax is an assessment of pharmacokinetic parameter
Area under the plasma concentration-time curve (AUC) for ARV-393 4 months from first drug dosing Assessment of pharmacokinetic parameter AUC
Minimum concentration (Cmin) for ARV-393 4 months from first drug dosing Cmin is an assessment of pharmacokinetic parameter
Maximum concentration (Cmax) for ARV-393 4 months from first drug dosing Cmax is an assessment of pharmacokinetic parameter
Oral clearance (CL/F) for ARV-393 4 months from first drug dosing CL/F is an assessment of pharmacokinetic parameter
Trial Locations
- Locations (1)
Clinical Trial Site
🇪🇸Salamanca, Spain