| Eligibility |
Inclusion Criteria:
1. Histological or cytological confirmation of the diagnosis of mCRC
2. Failure to respond or be intolerant of at least 2 prior regimens of standard
anti-cancer treatments (study treatment must be 3rd-line or greater for mCRC). Failed
prior treatments may include:
- Fluoropyrimidines-based chemotherapy
- Irinotecan-based chemotherapy
- Oxaliplatin-based chemotherapy
- Anti-Vascular Endothelial Growth Factor (VEGF) biological therapy
- Anti-Epidermal Growth Factor Receptor (EGFR) therapy, if RAS wild-type
- Immunotherapy (for example, nivolumab, pembrolizumab and ipilimumab), in
participants with Microsatellite Instability High/Deficient Mismatch Repair
(MSI-H/dMMR). Participants who had received adjuvant chemotherapy and had
recurrence during or within 6 months of completion of the adjuvant chemotherapy
would be considered as 1 prior line of therapy
3. Have progressed based on imaging during or within 3 months of the last administration
of most recent therapy
4. Have measurable disease, as defined by RECIST v1.1
5. Adequate bone marrow, renal, and hepatic function, as evidenced by the following
within 7 days prior to Cycle 1 Day 1
- Absolute neutrophil count (ANC) =1,500/mm3
- Platelets =75,000/mm3
- Hemoglobin =9.0 g/dL
- Creatinine clearance (according to Cockcroft-Gault Equation or by 24 hr urine
collection) > 50 mL/min and serum creatinine <1.0× upper limit of normal (ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) =3.0x ULN (=5.0 × ULN
for participants with liver involvement of their cancer)
- Bilirubin =1.5 × ULN
- Alkaline phosphatase =2.5 × ULN (=5 × ULN with liver involvement of their cancer)
- International normalized ratio (INR) / partial thromboplastin time (PTT) =1.5 ×
ULN (Participants currently under treatment with anti-thrombotic agents such as
warfarin or heparin with no abnormal coagulation values can participate in this
study)
6. Urinary protein <2+ on dipstick or routine urinalysis. If urine dipstick or routine
analysis indicates proteinuria = 2+, a 24-hour urine or urine protein/creatinine ratio
must be collected and must demonstrate <2 g of protein in 24 hours to allow
participation in the study.
7. Have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
Exclusion Criteria:
1. Prior treatment with rivoceranib or trifluridine/tipiracil
2. Prior treatment with other VEGFR small molecule inhibitors (for example, regorafenib)
3. Packed red blood cell transfusion or erythropoietin therapy within 14 days prior to
first dose of study drug
4. History of another malignancy within 3 years prior to Cycle 1 Day 1. A participant
with the following malignancies is eligible for this study if, in the opinion of the
Investigator, they do not pose a significant risk to life expectancy:
- Carcinoma of the skin without melanomatous features
- Curatively treated cervical carcinoma in situ
- Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in
situ (Tis)
- Thyroid papillary cancer with prior treatment
- Prostate cancer which has been surgically or medically treated and not likely to
recur within 3 years
6. Active renal dysfunction that requires dialysis treatments
7. Active cardiac disease including any of the following:
- Congestive heart failure New York Heart Association (NYHA) =Class 2
- Myocardial infarction less than 6 months before the start of Cycle 1 Day 1 of
treatment
8. Cardiac arrhythmias requiring antiarrhythmic therapy (beta-blockers or digoxin are
permitted)
9. History of uncontrolled hypertension (blood pressure =140/90 mmHg and/or change in
antihypertensive medication within 7 days prior to first dose of study drug)
10. History of antiangiogenic drug class-related severe adverse reactions, including
uncontrolled hypertension or others related to prior therapy discontinuation and/or
those that may indicate a higher risk to a participant' safety, in the Investigator's
opinion, if provided further antiangiogenic treatment.
11. History of vascular disease including arterial or venous embolic events (pulmonary
embolism), other than hypertension, within 6 months prior to Cycle 1 Day 1 (for
example, hypertensive crisis, hypertensive encephalopathy, stroke or transient
ischemic attack [TIA], or significant peripheral vascular diseases) that, in the
Investigator's opinion, may pose a risk to the participant on VEGF inhibitor therapy.
12. History of clinically significant thrombosis within 3 months prior to first dose
of study drug that, in the Investigator's opinion, may place the participant at risk
of side effects from antiangiogenics medications
13. History of bleeding diathesis or clinically significant bleeding within 14 days
prior to first dose of study drug
14. Therapy with systemic anticoagulant or antithrombotic agents within 7 days prior
to first dose of study drug that in the Investigator's opinion could interfere with
clotting. The maximum allowable daily dose of aspirin is 325 milligram (mg).
15. Participants with unstable seizure disorder requiring medication changes within 3
months of Cycle 1 Day 1 treatment
16. Untreated or active central nervous system (CNS) or leptomeningeal metastases.
Participants are eligible if metastases have been treated and participants are
neurologically returned to baseline or neurologically stable (expect for residual
signs and symptoms related to the CNS treatment) for at least 4 weeks prior to first
dose of study drug. In addition, participants must be either off corticosteroids, or
on a stable dose or decreasing dose of = 20 mg daily prednisone or
prednisone-equivalent. A baseline radiological assessment of the brain will be
performed on participants who have prior history of metastases with CNS involvement
17. History of clinically significant glomerulonephritis, biopsy-proven nephritis,
crystal nephropathy or other renal insufficiencies
18. Unresolved adverse reactions >Grade 1 excluding peripheral neuropathy or treatment
related myelosuppression
19. Known hypersensitivity to any of the study drugs, study drug classes, or any
components of study drug formulations
20. Inability to swallow oral medications
21. An active malabsorption condition, or any other condition that in the opinion of
the Investigator might affect the absorption of study drug
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