| Eligibility |
Key Inclusion Criteria:
- Fully understand the study and voluntarily sign the ICF;
- =18years of age;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
Dose Escalation Phase:
• Histologically or cytologically documented, locally advanced or metastatic solid
malignancy of any type (except squamous NSCLC) that has progressed on approved systemic
therapy, and for whom no effective therapy or standard of care exists. This cohort is
closed to enrollment.
Dose Expansion Phase:
- Cohort A: Histologically or cytologically documented, locally advanced or metastatic
solid malignancy of any type (except squamous NSCLC), that has progressed on approved
systemic therapy, and for whom no effective therapy or standard of care exists. This
cohort is closed to enrollment.
- Cohort B: Histologically or cytologically documented mCRC in patients that have
progressed on, or had intolerable toxicity with at least 1 FDA-approved third-line
systemic therapy (trifluridine/tipiracil or regorafenib). Patients must also have been
previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based
chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy for patients
who had RAS wild-type tumors. This cohort is currently enrolling.
- Cohort C: Histologically or cytologically documented adenocarcinoma of the colon or
rectum. Patients must have progressed on, or had intolerable toxicity to, at least 2
prior regimens of standard chemotherapy, but must not have received prior TAS-102 or
regorafenib. Prior therapy could have included adjuvant chemotherapy if a tumor had
recurred within 6 months after the last administration of treatment. Patients must
have been previously treated with fluoropyrimidine-, oxaliplatin-, and
irinotecan-based chemotherapy, an anti-VEGF biological therapy and, if RAS wild-type,
an anti-EGFR therapy
- Cohort D only: Histologically- or cytologically-confirmed Her2-negative, hormone
receptor positive (ER+ and/or PR+) breast cancer
- Cohort E only: Histologically- or cytologically- confirmed triple negative breast
cancer
Key Exclusion Criteria:
Patients will be excluded from the study, if any of the following criteria is met:
- Severe anemia, neutropenia, thrombocytopenia
- Moderate to severe renal or hepatic impairment
- Uncontrolled hypertension
- Risk of, or active hemorrhage: history or presence of active gastric/duodenal ulcer or
ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history
of perforation of fistulas; or any other condition that could possibly result in
gastrointestinal tract hemorrhage or perforation within 6 months prior to screening;
- History of a thromboembolic event (including deep vein thrombosis [DVT], pulmonary
embolism, stroke and/or transient ischemic attack) within 6 months prior to screening;
- Patients with squamous NSCLC;
- Clinically significant cardiovascular disease, including but not limited to acute
myocardial infarction or coronary artery bypass surgery within 6 months prior to
enrollment, severe or unstable angina pectoris, New York Heart Association Class
III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left
ventricular ejection fraction (LVEF) <50%;
- Patients who have ever received a VEGFR inhibitor, except for patients with mCRC
enrolled in the dose expansion phase;
- Systemic anti-neoplastic therapies or any investigational therapy within 4 weeks prior
to the first dose of study drug, including chemotherapy, radical radiotherapy,
hormonotherapy, biotherapy and immunotherapy;
- Systemic small molecule targeted therapies (eg, tyrosine kinase inhibitors) within 5
half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
- Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the
initiation of study drug;
- Brachytherapy (ie, implantation of radioactive seeds) within 60 days prior to the
first dose of study drug;
- Known human immunodeficiency virus (HIV) infection;
- Known clinically significant history of liver disease, including cirrhosis, current
alcohol abuse or active viral hepatitis. For patients with evidence of chronic
hepatitis B (HBV), the HBV viral load must be undetectable on suppressive therapy, if
indicated. Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV who are currently on treatment, they are
eligible if they have an undetectable HCV viral load;
- Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or
inferior vena cava.;
- Women who are pregnant or lactating;
- Brain metastases and/or spinal cord compression untreated with surgery and/or
radiotherapy, and without clinical imaging evidence of stable disease for 14 days or
longer; patients requiring steroids within 4 weeks prior to start of study treatment
will be excluded;
- No other malignancy, except for non-melanoma skin cancer, during the 5 years prior to
screening;
- Inability to take medication orally, dysphagia or an active gastric ulcer resulting
from previous surgery (eg, gastric bypass) or a severe gastrointestinal disease, or
any other condition that investigators believe may affect absorption of the
investigational product;
- Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory
result, or any other condition that investigators suspect may prohibit use of the
investigational product, affect interpretation of study results, or put the patient at
undue risk of harm based on the investigator's assessment;
- Known hypersensitivity to fruquintinib or any of its excipients.
- For Cohort C only: patients who have been previously treated with TAS-102 or
regorafenib
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