A Phase 1b Trial of Mavorixafor, an Oral CXCR4 Antagonist, in Combination with Ibrutinib in Patients with Waldenstrom’s Macroglobulinemia (WM) Whose Tumors Express Mutations in MYD88 and CXCR4

The primary objective of the study is to establish a pharmacologically active dose of
mavorixafor in combination with ibrutinib based on pooled safety, clinical response,
pharmacokinetic (PK) and pharmacodynamic (PD) data to select the recommended dose for a
randomized registrations trial.

Inclusion Criteria:

- Participants must be able to sign informed consent

- Participants must have a clinicopathological diagnosis of WM and must meet the
criteria for treatment using consensus panel criteria from the Second International
Workshop on Waldenstrom's Macroglobulinemia

- Participant' WM must have confirmed MYD88L265P and CXCR4WHIM mutations

- Participants must have measurable disease, defined as the presence of serum IgM with a
minimum IgM level of greater than or equal to (≥) 2 * the upper limit of normal (ULN)

- Participants may be treatment naïve or have received up to 3 prior treatment regimens
for WM

- Participants must have an ECOG performance status of 0 or 1

- Participants must meet the following organ and bone marrow requirements:

i) Absolute neutrophil count greater than (>) 1,000/microliter (μL) ii) Platelet count
≥50,000/μL (platelet transfusion-independent) iii) Hgb ≥8 grams/deciliter (gm/dL) iv)
Aspartate aminotransferase and alanine aminotransferase less than or equal to (≤) 2.5
* the ULN and serum total bilirubin ≤1.5 * the ULN, unless secondary to known
Gilbert's Syndrome or hepatic infiltration by WM, in which case the total bilirubin
must be ≤3 * the ULN and direct bilirubin ≤1.5 × the ULN v) Serum lipase ≤1.5 * the
ULN vi) Serum creatinine ≤2 * the ULN or a creatinine clearance of ≥30 milliliters
(ml)/minute based on the Cockcroft-Gault equation

- Women of child-bearing potential (WOCBP) must have a negative pregnancy test

- WOCBP who are heterosexually active and male participants with female sexual partners
of childbearing potential must agree to use an effective method of contraception (for
example; oral contraceptives, double-barrier methods such as a condom and a diaphragm,
intrauterine device) during the study and for 4 weeks after the last dose of study
medication, or to abstain from sexual intercourse for this time; a woman not of
childbearing potential is one who has undergone a bilateral oophorectomy or who is
postmenopausal, defined as the absence of menstrual periods for 12 consecutive months

- Participants must be willing and capable of complying with the requirements of the
study

Exclusion Criteria:

- Participants with symptomatic hyperviscosity syndrome; participants who undergo
plasmapheresis for hyperviscosity may be considered for enrollment once IgM level is
under 4,000 mg/dl

- Participants who have known hypersensitivity to mavorixafor or any of its components
or to ibrutinib

- Participants who have previously received a CXCR4 inhibitor or a BTK inhibitor

- Participants who are pregnant or breastfeeding

- Participants with an infection requiring intravenous antibiotics or hospitalization at
the scheduled time of the first administration of protocol therapy

- Participants with glycated hemoglobin (HbA1c) >6.5%

- Participants with central nervous system (CNS) lymphoma; participants with suspected
CNS lymphoma should undergo appropriate diagnostic studies (magnetic resonance
imaging, lumbar puncture) before enrollment to determine if CNS lymphoma is present

- Participants with ongoing acute clinical AEs of National Cancer Institute Common
Terminology Criteria for AEs (NCI CTCAE) Grade >1 resulting from prior cancer
therapies or participants receive prior chemotherapy within 2 weeks of initial dosing
or prior autologous hematopoietic stem cell transplantation (auto-HSCT) within 6 weeks
of initial dosing

- Participants with a history of, or positive serologies for, human immunodeficiency
virus (HIV), hepatitis B or hepatitis C infection (participants with HBsAb positivity
due to a hepatitis B virus [HBV] vaccination are eligible)

- Participants who have had within the past 6 months, the occurrence or persistence of
one or more of the following medical conditions that could not be controlled with
usual medical care (for example; required emergency care or hospitalization):
hypertension, diabetes, unstable angina, seizure disorder, or myocardial infarction

- Participants with clinically significant cardiac disease, including congestive heart
failure consistent with New York Heart Association Class 3 or 4; uncontrolled
hypertension, clinically significant angina, clinically significant arrythmias
including a history of atrial fibrillationin the last 2 years, corrected QT interval
using Fridericia formula of >470 milliseconds (msec) or a history of prolonged QT
syndrome

- Participants who have had within the past 6 months the occurrence of one or more of
the following events: cerebrovascular accident, deep vein thrombosis, pulmonary
embolism, hemorrhage (NCI CTCAE Grade 3 or Grade 4), or chronic liver disease (meeting
criteria for Child-Pugh Class B or C)

- Participants with prior organ transplantation (prior auto-HSCT are eligible)

- Participants who have an uncontrolled bleeding disorder or require an anticoagulant at
the time of study treatment

- Participants with active autoimmune disease requiring systemic steroid administration

- Participants with active second malignancies. (except: malignancies that were treated
curatively and have not recurred within 2 years prior to study treatment; completely
resected basal cell and squamous cell skin cancers; any non-hematological malignancy
considered to be indolent and that has never required therapy; and completely resected
carcinoma in situ of any type)

- Participants who have received an investigational agent within 5 half-lives of the
agent; if the half-life of the agent is unknown, patients must wait 4 weeks

- Participants who require strong or moderate inhibitors or inducers of CYP3A4 and
potent P-gp inhibitors

- Participants who require medications which are classified as sensitive CYP2D6
substrates

- Participant who have received in the 2 weeks preceding the first dose of protocol
treatment, any of the following agents:

i) Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating
factor ii) Systemic corticosteroids in a dose of >10 mg equivalent of prednisone
daily; topical, ophthalmic, intranasal, and inhalational corticosteroids are permitted
iii) Any other immunomodulating agents, including but not limited to interferon alpha,
interleukin (IL)-2, mycophenolate, antibodies to tumor necrosis factor (TNF)-α,
soluble TNF receptors, Janus kinase inhibitors, or IL-23 antagonists

- Participants with any other medical, personal, social, or psychiatric condition that,
in the opinion of the Investigator, may potentially compromise the safety or
compliance of the participant or precludes the participant's participation in the
study