Addition of X4P-001 to Nivolumab Treatment in Patients With Renal Cell Carcinoma

Treatment with immune checkpoint inhibitors, such as nivolumab, may result in the generation
of anti-tumor immune responses. However, the objective radiological response in advanced RCC
patients was only 21.5%. Therefore, it is important to identify additional therapies that
could augment the anti-tumor immune activity of checkpoint inhibitors, resulting in an
increase in the number of patients able to achieve a radiological response to treatment.

While checkpoint inhibitors facilitate activation of cytotoxic T cells, the agents do not
impact T cell trafficking. X4P-001, a CXCR4 antagonist, is hypothesized to impact the
trafficking of immune cell types, for example, decreasing myeloid-derived suppressor cells
and increasing cytotoxic T cells at the tumor. Giving X4P-001 treatment in combination with
nivolumab is hypothesized to increase the clinical response to by providing an influx of T
cells that can be further activated by the checkpoint inhibitor. Additionally, CXCR4 plays a
role in trafficking of endothelial progenitor cells which mediate angiogenesis. RCC is known
to be responsive to anti-angiogenic agents, and thus X4P-001 targets a second mechanism of
tumor growth inhibition.

Inclusion Criteria:

- Histologically confirmed diagnosis of Renal Cell Carcinoma with a documented clear
cell component (ccRCC)

- Currently receiving nivolumab and considered by Investigator to have the potential to
derive clinical benefit from continuing treatment with nivolumab.

- Based on RECIST v1.1 criteria on current nivolumab treatment (prior to initiation of
this study), has a best response of confirmed stable disease (SD) or confirmed
progressive disease (PD). Confirmed SD or confirmed PD refers to a response that is
confirmed by a 2nd scan which is at least 4 weeks apart from the previous scan.

- At least one extra-renal measurable target lesion meeting the criteria of RECIST
version 1.1

- Agree to use contraception from screening, through the study, and for at least 5
months after the last dose of nivolumab as follows: for women of childbearing
potential agree to use highly effective contraceptive methods; for males, agree to use
a condom with sexual partner.

Exclusion Criteria:

- Pregnant or nursing

- Life expectancy of less than 3 months

- ECOG PS ≥2 (Eastern Cooperative Oncology Group [ECOG] criteria)

- NYHA Class III or IV, uncontrolled hypertension, or clinically significant arrhythmia

- Previously received X4P-001

- Has a second malignancy. 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 malignancy considered to be indolent and that has
never required therapy; and completely resected carcinoma in situ of any type.

- Has active central nervous system (CNS) metastases (including evidence of cerebral
edema by MRI, or progression from prior imaging study, or any requirement for
steroids, or clinical symptoms of/from CNS metastases) within 28 days prior to study
treatment. Subjects with known CNS metastases must have a baseline MRI scan within 28
days of study treatment.

- Ongoing clinical adverse events NCI CTCAE Grade >2 resulting from prior cancer
therapies

- Known history of HIV or AIDS; or positive test for hepatitis C virus (HCV), or
hepatitis B surface antigen (HBsAg)

- History of clinically significant or uncontrolled cardiac, hepatic, or pulmonary
disease

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

- Inadequate hematologic, hepatic, or renal function