A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.

NCT06393738
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
329
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Lead sponsor
Arvinas Inc.
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Start date
2024-09-05
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Number of sites
19
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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.
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Short title
A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma.
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Official title
A Phase 1 First in Human Study of ARV-393 in Adult Participants With Advanced Non-Hodgkin's Lymphoma
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-03-01
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First posted
2024-05-01
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Registry last updated
2026-08-26
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Primary completion date
2028-03-01
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Start date
2024-09-05
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Participants
329
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Participant count basis
Estimated
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Planned participants
329
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Protocol amendments
2
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Number of sites
19
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Arvinas Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06393738
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ClinicalTrials.gov ID
NCT06393738
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Registry record
Open registry record
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Allocation
Not applicable
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Incidence of Dose Limiting Toxicities During First 28 Days

    Timeframe: 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)

  2. Percentage of Participants With Adverse Events Characterized by Severity, Seriousness, and Relationship to Study Drug as a Measure of Safety and Tolerability

    Timeframe: 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

  3. Number of Participants With Abnormal Vital Signs, Abnormal ECG Readings (QT Interval) and Abnormal Laboratory Parameters

    Timeframe: 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

  4. 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: 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

  1. Area Under the Curve to the End of the Dosing Period (Auctau) for ARV-393

    Timeframe: 4 months from first drug dosing

    Assessment of pharmacokinetic parameter AUC

  2. Area Under the Concentration Versus Time Curve, from 0 To Last Measurable Concentration (AUC0-Last) for ARV-393

    Timeframe: Time Frame: 4 months from first drug dosing

    Assessment of pharmacokinetic parameter AUC

  3. Maximum Concentration (Cmax) for ARV-393

    Timeframe: 4 months from first drug dosing

    Cmax is an assessment of pharmacokinetic parameter

  4. Minimum Concentration (Cmin) for ARV-393

    Timeframe: 4 months from first drug dosing

    Cmin is an assessment of pharmacokinetic parameter

  5. Time to Maximum Concentration (Tmax) for ARV-393

    Timeframe: 4 months from first drug dosing

    Tmax is an assessment of pharmacokinetic parameter

  6. Oral Clearance (CL/F) for ARV-393

    Timeframe: 4 months from first drug dosing

    CL/F is an assessment of pharmacokinetic parameter

  7. Volume of Distribution (Vd/F) for ARV-393

    Timeframe: 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.

  8. 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

    Timeframe: 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.

  9. 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

    Timeframe: 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.

  10. 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

    Timeframe: 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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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%.

Sources for eligibility
clinicaltrials.gov

  • Clinical Trial SiteNew Haven, United StatesRecruiting
  • Clinical Trial SiteMiami, United StatesRecruiting
  • Clinical Trial SiteDetroit, United StatesRecruiting
  • Clinical Trial SiteNew Brunswick, United StatesRecruiting
  • Clinical Trial SiteNew York, United StatesRecruiting
  • Clinical Trial SiteNew York, United StatesRecruiting
  • Clinical Trial SiteCleveland, United StatesRecruiting
  • Clinical Trial SiteNashville, United StatesWithdrawn
  • Clinical Trial SiteHouston, United StatesRecruiting
  • Clinical Trial SiteCharlottesville, United StatesRecruiting
  • Clinical Trial SiteToronto, CanadaRecruiting
  • Clinical Trial SiteMontreal, CanadaRecruiting
  • Clinical Trial SiteCopenhagen, DenmarkRecruiting
  • Clinical Trial SiteOdense C, DenmarkRecruiting
  • Clinical Trial SiteEl Palmar, SpainRecruiting
  • Clinical Trial SitePamplona, SpainRecruiting
  • Clinical Trial SiteBarcelona, SpainRecruiting
  • Clinical Trial SiteMadrid, SpainRecruiting
  • Clinical Trial SiteSalamanca, SpainRecruiting
Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-510136-36-00
Sources for references
clinicaltrials.gov

Related records

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