Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Duvortuxizumab (JNJ-64052781) Plus Ibrutinib in Lymphoma

This is an open-label (identity of study drug will be known to participant and study staff),
multicenter (when more than one hospital or medical school team work on a medical research
study), Phase 1b study. The purpose of this study is to see if duvortuxizumab in combination
with ibrutinib is safe and useful for treating participants with B-cell malignancies. This
study will be conducted in 2 parts: Part 1: Dose Optimization and Part 2: Dose Expansion.
Part 1 will determine what dose of duvortuxizumab can be given safely with the standard dose
of ibrutinib to participants with previously treated B-cell malignancies. Part 2 will look at
how previously treated DLBCL, FL, MCL, and CLL participants respond to a safe dose of
duvortuxizumab in combination with ibrutinib. Part 2 will also test whether the dose from
Part 1 is an effective cancer therapy. The study consists of a Screening Phase, an ibrutinib
Run-In Phase (Part 2 only), a combination (duvortuxizumab plus ibrutinib) Treatment Phase
(Day 1, Cycle 1 and continues until the completion of the End-of-Treatment Visit),
End-of-Treatment Visit (30 days (+7 days) after the last dose of study drug), and
Post-treatment Follow-up Phase. The end of the study will be defined as 12 months after the
last participant has received the first dose of study treatment. Participants' safety will be
monitored throughout the study.

Inclusion Criteria:

- The participant has a B-cell malignancy (diffuse large B-cell lymphoma [DLBCL],
follicular lymphoma [FL], mantle cell lymphoma [MCL], or chronic lymphocytic leukemia
[CLL]) with tumor progression following at least one (MCL and CLL) or two (DLBCL and
FL) prior standard therapies

- The participant has a radiographically measurable tumor that requires treatment
according to the treating physician

- The participant is able to carry out daily life activities with significant difficulty

- The participant has adequate organ and blood cell counts

- Sexually active participants must use medically acceptable methods of contraception
during the course of the study

Exclusion Criteria:

- The participant has a brain tumor or significant side effects, including severe
neurological side effects, from a previous anti-cancer treatment

- Current severe, uncontrolled systemic disease including an ongoing, active infection
or history of clinically significant heart problems

- History of autoimmune disease, allogeneic hematopoietic stem cell transplant, or organ
transplant

- The participant has received any of the following: ibrutinib or other Bruton's
tyrosine kinase (BTK) inhibitor at any time; an agent targeting CD19-positive cells or
CD3-expressing T cells at any time; or warfarin, a vitamin K antagonist, or a blood
transfusion (red blood cells and/or platelets) within 1 week of starting the study

- The participant is pregnant, breastfeeding, or planning to become pregnant or father a
child