Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Inclusion Criteria:

- Measurable disease by computed tomograph (CT)/ and/or positron-emission tomography CT
(PET-CT)

- A) Dose Escalation Stage: Confirmed diagnosis of relapsed or refractory Non-Hodgkin
Lymphoma (NHL) treated with prior treatment for lymphoid malignancy comprising of at
least 1 regimen containing a therapeutic anti-CD20 antibody (eg, rituximab,
ofatumumab, GA-101) and at least 2 prior combination chemotherapy regimens (or
autologous stem cell transplant) , or treated with 1 prior combination chemotherapy
regimen in patients without an approved second-line therapy option, requiring
treatment in the opinion of the treating physician

- B) Dose Expansion Cohorts:

- Expansion Cohort A: Relapsed or refractory DLBCL treated with prior treatment
for lymphoid malignancy comprising of at least 1 regimen containing a
therapeutic anti-CD20 antibody (eg, rituximab, ofatumumab, GA-101) and at least
2 prior combination chemotherapy regimens or autologous stem cell transplant, or
treated with 1 prior combination chemotherapy regimen in patients without an
approved second-line therapy option, requiring treatment in the opinion of the
treating physician

- Expansion Cohort B: Diagnosis of relapsed or refractory B-cell NHL (other than
DLBCL) treated with prior treatment for lymphoid malignancy comprising of at
least 1 regimen containing a therapeutic anti-CD20 antibody (eg, rituximab,
ofatumumab, GA-101) and at least 2 prior combination chemotherapy regimens or
autologous stem cell transplant, or treated with 1 prior combination
chemotherapy regimen in patients without an approved second-line therapy option,
requiring treatment in the opinion of the treating physician

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky
performance status ≥ 70

- Required screening laboratory data (within 2 weeks prior to administration of study
drug) as shown in study protocol.

- Adequate organ function defined by the screening laboratory inclusion listed below
and Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO or multigated
acquisition (MUGA)

- Discontinuation of all therapy (including radiotherapy, chemotherapy, tyrosine kinase
inhibitors (TKIs), immunotherapy, or investigational therapy for the treatment of
cancer at least 2 weeks prior to the initiation of study therapy

- All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before
enrollment, with the exception of alopecia (any grade permitted)

- For female individuals of childbearing potential, willingness to use a protocol-
recommended method of contraception

- For male individuals having intercourse with females of childbearing potential,
willingness to abstain from heterosexual intercourse or use a protocol- recommended
method of contraception

- In the judgment of the investigator, participation in the protocol offers an
acceptable benefit-to-risk ratio when considering current disease status, medical
condition, and the potential benefits and risks of alternative treatments for the
individual's NHL

- Willingness to comply with scheduled visits, drug administration plan, imaging
studies, laboratory tests, other study procedures, and study restrictions

- Have the ability to understand and sign a written informed consent form, which must
be obtained prior to initiation of study procedures

Exclusion Criteria:

- Diagnosis of Primary Mediastinal Large B-cell Lymphoma

- A life threatening illness, medical condition or organ system dysfunction which, in
the investigator's opinion, could compromise the individual's safety or interfere
with the absorption or metabolism of ENTO

- Active or symptomatic central nervous system (CNS) disease or epidural involvement

- Uncontrolled intercurrent illness including, but not limited to, unstable angina
pectoris or psychiatric illness/social situations that would limit compliance with
study requirements

- Current/ongoing Neuropathy (sensory or motor) Grade > 1 or any history of Grade ≥ 3
neuropathy with prior Vincristine or chemotherapy exposure (documentation by history
is adequate to exclude)

- Contraindication to receive vincristine or any planned protocol-specified
chemotherapy

- Eligible for autologous stem cell transplant

- History of myelodysplastic syndrome, allogeneic stem cell or solid organ
transplantation

- History of any other prior lymphoid malignancy other than the registrational
histology or any other non-lymphoid malignancy except for the following: adequately
treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma
in situ, superficial bladder cancer, asymptomatic prostate cancer without known
metastatic disease and with no requirement for therapy or requiring only hormonal
therapy and with normal prostate specific antigen for ≥ 1 year prior to the start of
study drug, or any other cancer that has been in complete remission without treatment
for ≥ 5 years prior to enrollment

- Known hypersensitivity or intolerance to any of the active substances or excipients
in the formulations for ENTO

- Evidence of uncontrolled systemic bacterial, fungal, or viral infection at the start
of study drug

- Ongoing drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic
active Hepatitis B Virus (HBV), HIV, alcoholic liver disease, non-alcoholic
steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by
cholelithiasis, cirrhosis of the liver, or portal hypertension

- Current therapy with proton pump inhibitors

- Pregnancy or breastfeeding

- Ongoing active pneumonitis

- Prior treatment with a spleen tyrosine kinase (SYK) inhibitor