A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC

This is a multicenter, single arm, safety lead-in, Phase 2 study, using Simon's 2 stage
design evaluating the safety and efficacy of TAS-102 plus nivolumab in patients with
Microsatellite-stable refractory metastatic colorectal cancer

Stage 1: Patients will be enrolled and after Cycle 1 treatment, they will be evaluated for
the safety and tolerability of the combination therapy. Assuming a tolerated dose is
confirmed additional patients evaluable for response will be enrolled and followed for a
minimum of 6 months and there will be an interim analysis to assess the safety and efficacy
to determine whether the second stage will open for enrollment.

Stage 2: Additional patients evaluable for response assessment will be enrolled and followed
for a minimum of 6 months.

Inclusion Criteria:

1. Has provided written informed consent.

2. Patient with confirmed histologically proven metastatic or locally advanced colorectal
adenocarcinoma who are MSS (ie, not MSI) based on either an analysis of tissue from a
prior biopsy or based on tissue from a new biopsy.

3. Patient with the presence of at least 1 lesion with measurable disease as defined by
10 mm in the longest diameter for a soft tissue lesions or 15 mm in the short axis for
a lymph node by RECIST and irRC criteria for a response assessment.

4. Patient has received at least 2 prior lines of standard chemotherapies for mCRC and is
refractory to or failing those chemotherapies.

5. Age ≥ 18 years.

6. Eastern Cooperative Oncology Group performance status of 0 to 1

7. Life expectancy of ≥ 4 months.

8. Has adequate organ function

9. Women of childbearing potential must have a negative pregnancy test (urine or serum)
within 7 days before starting study drugs. Is able to take medications orally

Exclusion Criteria:

1. Has a serious illness or medical condition

2. Treatment with any of the following within the specified time frame before enrollment:

1. Major surgery within the past 4 weeks (the surgical incision should be fully
healed before study drug administration).

2. Any anticancer therapy within the past 3 weeks before enrollment.

3. Extended field radiation within the past 4 weeks or limited field radiation
within the past 2 weeks before enrollment.

4. Any investigational drug/device received within the past 4 weeks or 5 times the
half-life (whichever is shorter) before enrollment.

3. Previous treatment with TAS-102.

4. Prior treatment with anti-PD-1, anti- PD-L1, anti programmed cell death ligand 2,
anti-CD137, anti-OX-40, anti CD40, anti cytotoxic T lymphocyte associated antigen-4
antibodies, or any other immune checkpoint inhibitors.

5. Unresolved toxicity of ≥ Common Terminology Criteria for Adverse Events version
(CTCAE) version 4.03 grade 2 attributed to any prior therapies (excluding anemia,
alopecia, skin pigmentation, and platinum induced neurotoxicity).

6. Prior events of immune-mediated pneumonitis, immune-mediated colitis, immune-mediated
hepatitis, immune-mediated endocrinopathies, immune mediated nephritis and renal
dysfunction, immune mediated rash, immune mediated encephalitis, and history of
infusion reactions to nivolumab.

7. Known or assumed hypersensitivity to TAS-102 or nivolumab or any of its ingredients,
including polysorbate 80-containing infusion.

8. Previous severe hypersensitivity reaction to treatment with another mAb.

9. Pregnant or lactating female.

10. Inappropriate for entry into this study in the judgment of the investigator.