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

Arvinas

Status and phase: Enrolling; Phase 1

Conditions: Relapsed/Refractory (R/R) Angioimmunoblastic T-cell Lymphoma (AITL); Relapsed/Refractory (R/R) Mature B Cell Non Hodgkin Lymphoma (NHL)

Treatments: Drug: ARV-393; Drug: Glofitamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06393738

2023-510136-36-00 (EU Trial (CTIS) Number)

ARV-393-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 255 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• Current or past history of peripheral eosinophilia, hypereosinophilic syndrome (HES), organ-specific eosinophilic disorder, or drug reaction with eosinophilia and systemic symptoms (DRESS).

• Prior allogeneic stem cell transplant (SCT) or solid organ transplantation.

• 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%.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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255 participants in 4 patient groups

Part A Monotherapy Dose escalation

Experimental group

Description:

Participants with R/R NHL will receive ARV-393 dose escalation beginning at dose level 1

Treatment:

Drug: ARV-393

Part B Monotherapy: Dose expansion/optimization

Experimental group

Description:

Dose expansion and optimization of ARV-393 will be conducted in Part B to determine the recommended phase 2 dose (RP2D) for participants with R/R NHL

Treatment:

Drug: ARV-393

Part C Combination therapy: Dose escalation

Experimental group

Description:

Participants with R/R diffuse large B-cell lymphoma (DLBCL) will receive ARV-393 in combination with glofitamab, beginning at an ARV-393 dose informed by the Part A. Glofitamab will be given per labelled prescribing information. Part C will be conducted in non-USA centers.

Treatment:

Drug: Glofitamab

Drug: ARV-393

Part D Combination therapy: Dose expansion/optimization

Experimental group

Description:

Part D will be an optimization of ARV-393 in combination with glofitamab to determine a potential RP2D for ARV-393 in the combination regimen. Part D will be conducted in non-USA centers in participants with R/R DLBCL.

Treatment:

Drug: Glofitamab

Drug: ARV-393