A Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

An Open-Label Phase 1/2 Study of Itacitinib (INCB039110) in Combination With Ibrutinib in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

The purpose of this study is to evaluate the safety/tolerability and efficacy of itacitinib in combination with ibrutinib in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Inclusion Criteria:

• Histologically documented diagnosis of DLBCL.

  • Phase 1: any DLBCL subtype.
  • Phase 2: activated B-cell or unclassifiable subtypes confirmed by immunohistochemistry using the Hans algorithm

• Relapsed or refractory DLBCL, defined as having received at least 1 but no more than 3 prior treatment regimens and ineligible for high-dose chemotherapy/autologous stem cell transplant.

• Fluorodeoxyglucose-avid disease (based on local evaluation) per the Lugano Classification. Fluorodeoxyglucose-avid disease is defined as disease with a 5-point scale score of 4 or 5.

• Archived tumor tissue (block or 15-20 unstained slides) available, or be willing to undergo an incisional or excisional lymph node biopsy of accessible adenopathy (or, in less accessible lymph nodes, 4 to 8 core biopsies).

• At least 1 measurable (≥ 2 cm in longest dimension) lesion on CT scan or magnetic resonance imaging (MRI).

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Exclusion Criteria:

• Transformed DLBCL or DLBCL with coexistent histologies (eg, follicular or mucosa-associated lymphoid tissue lymphoma).
• Primary mediastinal (thymic) large B-cell lymphoma.
• Known central nervous system lymphoma (either primary or metastatic).
• Allogeneic stem cell transplant within the previous 6 months, or active graft versus host disease following allogeneic transplant.
• Use of immunosuppressive therapy within 28 days of starting study treatment. Immunosuppressive therapy includes but is not limited to cyclosporine A, tacrolimus, or high-dose corticosteroids. Subjects receiving corticosteroids must be at a dose level ≤ 10 mg/day within 7 days of initiating study treatment.
• Prior or concurrent therapy with a Janus kinase inhibitor or Bruton's tyrosine kinase inhibitor