Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL), Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)
Conditions
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
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.
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.
Interventions
DRUGARV-393
Oral daily dose of ARV-393 at a specified dose level
DRUGGlofitamab
Glofitamab infusion per labelled prescribing information
Sponsors
Arvinas Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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), 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; * 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%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities During First 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 | 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 | 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 | 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 | Shifts in vital signs, ECGs, and laboratory parameters from study baseline |
| 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 | 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 | Incidence of Grade 3 and Grade 4 clinical laboratory abnormalities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393 | 4 months from first drug dosing | Assessment of pharmacokinetic parameter AUC |
| 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 | Assessment of pharmacokinetic parameter AUC |
| Maximum Concentration (Cmax) for ARV-393 | 4 months from first drug dosing | Cmax is an assessment of pharmacokinetic parameter |
| Minimum Concentration (Cmin) for ARV-393 | 4 months from first drug dosing | Cmin is an assessment of pharmacokinetic parameter |
| Time to Maximum Concentration (Tmax) for ARV-393 | 4 months from first drug dosing | Tmax 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 |
| 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. |
| 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 | Approximately 2 years | 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. |
| 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 | Approximately 2 years | 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. |
| 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 | 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 the study intervention. |
Countries
Australia, Canada, Denmark, Spain, United States
Contacts
CONTACTArvinas Operations, Inc.
Outcome results
None listed