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.
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).
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.
Sequential
ARV-393
DrugOral daily dose of ARV-393 at a specified dose level
Glofitamab
DrugGlofitamab infusion per labelled prescribing information
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)
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
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
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
Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393
Assessment of pharmacokinetic parameter AUC
Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393
Assessment of pharmacokinetic parameter AUC
Maximum Concentration (Cmax) for ARV-393
Cmax is an assessment of pharmacokinetic parameter
Minimum Concentration (Cmin) for ARV-393
Cmin is an assessment of pharmacokinetic parameter
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