A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma
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.
Arms & interventions
- DrugARV-393
Oral daily dose of ARV-393 at a specified dose level
- DrugGlofitamab
Glofitamab infusion per labelled prescribing information
Outcome measures
Primary
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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393
Time frame: 4 months from first drug dosing
Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393
Time frame: Time Frame: 4 months from first drug dosing
Maximum Concentration (Cmax) for ARV-393
Time frame: 4 months from first drug dosing
Minimum Concentration (Cmin) for ARV-393
Time frame: 4 months from first drug dosing
Time to Maximum Concentration (Tmax) for ARV-393
Time frame: 4 months from first drug dosing
Oral Clearance (CL/F) for ARV-393
Time frame: 4 months from first drug dosing
Volume of Distribution (Vd/F) for ARV-393
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Approximately 2 years
Eligibility criteria
Study locations (8)
Clinical Trial Site
New Haven, Connecticut, 06510
Clinical Trial Site
Detroit, Michigan, 48201
Clinical Trial Site
New Brunswick, New Jersey, 10065
Clinical Trial Site
New York, New York, 10016
Clinical Trial Site
New York, New York, 10021
Clinical Trial Site
Cleveland, Ohio, 44122
Clinical Trial Site
Nashville, Tennessee, 37203
Clinical Trial Site
Houston, Texas, 77030