Clinical trial NCT06393738: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.
Official title: A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)
Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL)
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
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-01
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The study will be initiated with the starting dose. The dose may be escalated to higher dose cohorts or de-escalated to lower dose cohorts based upon the safety and tolerability and as per a Cohort Review Committee recommendation. Backfill cohorts may be initiated at a previously cleared dose with select NHL subtypes
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence of Dose limiting toxicities during Cycle 1 (28 days)
timeFrame: 28 days from first study dosing
measure: Percentage of participants with Adverse Events characterized by severity, seriousness, and relationship to study drug as a measure of safety and tolerability
timeFrame: From the study baseline to at least 30 days after last dose of ARV-393
measure: Number of participants with abnormal vital signs, abnormal ECG readings ( QT interval) and abnormal laboratory parameters.
timeFrame: From the study baseline to at least 30 days after last dose of ARV-393
measure: 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.
timeFrame: From the study baseline to at least 30 days after last dose of ARV-393
Secondary outcomes:
measure: Area under the plasma concentration-time curve (AUC) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Maximum concentration (Cmax) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Minimum concentration (Cmin) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Time to maximum concentration (Tmax) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Oral clearance (CL/F) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Volume of distribution (Vd/F) for ARV-393
timeFrame: 4 months from first drug dosing
measure: Overall response rate (ORR) in participants
timeFrame: Approximately 2 years
measure: Complete response rate (CRR)
timeFrame: Approximately 2 years
measure: Duration of response (DOR)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Detroit
country: United States
facility: Clinical Trial Site
state: Michigan
city: New Brunswick
country: United States
facility: Clinical Trial Site
state: New Jersey
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Montreal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Copenhagen
country: Denmark
facility: Clinical Trial Site
city: Odense C
country: Denmark
facility: Clinical Trial Site
city: El Palmar
country: Spain
facility: Clinical Trial Site
state: Murcia
city: Pamplona
country: Spain
facility: Clinical Trial Site
state: Navarra
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Salamanca
country: Spain
facility: Clinical Trial Site
Study officials:
References: