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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
255
Oral daily dose of ARV-393 at a specified dose level
Glofitamab infusion per labelled prescribing information
Clinical Trial Site
New Haven, Connecticut, United States
RECRUITINGClinical Trial Site
Detroit, Michigan, United States
RECRUITINGClinical Trial Site
New Brunswick, New Jersey, United States
RECRUITINGClinical Trial Site
New York, New York, United States
RECRUITINGClinical Trial Site
New York, New York, United States
RECRUITINGClinical Trial Site
Cleveland, Ohio, United States
RECRUITINGClinical Trial Site
Nashville, Tennessee, United States
RECRUITINGClinical Trial Site
Houston, Texas, United States
RECRUITINGClinical Trial Site
Toronto, Ontario, Canada
RECRUITINGClinical Trial Site
Montreal, Quebec, Canada
RECRUITING...and 7 more locations
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
Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393
Assessment of pharmacokinetic parameter AUC
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
Assessment of pharmacokinetic parameter AUC
Time frame: Time Frame: 4 months from first drug dosing
Maximum Concentration (Cmax) for ARV-393
Cmax is an assessment of pharmacokinetic parameter
Time frame: 4 months from first drug dosing
Minimum Concentration (Cmin) for ARV-393
Cmin is an assessment of pharmacokinetic parameter
Time frame: 4 months from first drug dosing
Time to Maximum Concentration (Tmax) for ARV-393
Tmax is an assessment of pharmacokinetic parameter
Time frame: 4 months from first drug dosing
Oral Clearance (CL/F) for ARV-393
CL/F is an assessment of pharmacokinetic parameter
Time frame: 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.
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
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.
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
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.
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
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.
Time frame: Approximately 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.