| Eligibility |
Inclusion Criteria:
1. Documented primary diagnosis of histologic- or cytologic-confirmed solid tumor cancer
inclusive of gastric adenocarcinoma, renal cell carcinoma, melanoma, non-small cell
lung cancer (NSCLC), breast cancer, angiosarcoma, leiomyosarcoma, synovial sarcoma,
and alveolar soft part sarcoma or other solid tumor for which anti-Vascular
endothelial growth factor receptor (VEGFR)2 targeted therapy could be applicable.
2. Locally advanced unresectable or metastatic disease.
3. Nivolumab treatment naive and able to begin nivolumab treatment concurrently with
initiation of apatinib or have received at least 3 doses of nivolumab treatment and
are continuing nivolumab therapy.
4. 1 or more measurable lesions per RECIST v1.1.
5. Participants who have adequate bone-marrow, renal and liver function including:
1. Hematologic: absolute neutrophil count = 1,500/ cubic millimetre (mm^3),
platelets= 100,000/mm^3, hemoglobin = 9.0 grams (g)/ per decilitre (dL) (blood
transfusion to meet the inclusion criteria within 2 weeks is not allowed).
2. Renal: serum creatinine < 1.5× upper limit of normal (ULN); urinary protein
should be< 2+ on dipstick or routine urinalysis. If urine dipstick or routine
analysis indicates proteinuria = 2+, then 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.
3. Hepatic: serum bilirubin < 1.5× ULN, aspartate transaminase (AST) and alanine
transaminase (ALT) = 3.0× ULN(= 4.0× ULN, if with liver metastases).
4. Blood coagulation tests: Partial thromboplastin time (PTT) and international
normalized ratio (INR) = 1.5× ULN and = 1.5×ULN, respectively.
6. Eastern Cooperative Oncology Group (ECOG) performance status are evaluated to be = 1
(Participants with ECOG performance status of 2 may be enrolled only with advance
review and written approval by the medical monitor).
7. Expected survival of = 12 weeks, in the judgement of the investigator.
8. Ability to swallow the study drug tablets.
Exclusion Criteria:
1. History of another malignancy within 2 years prior to enrollment, unless it does not
pose a significant risk to life expectancy as per the investigator.
2. Central nervous system (CNS) metastases as shown by radiology records or clinical
evidence of symptomatic CNS involvement in the last 3 months prior to enrollment.
Participants are eligible if metastases have been treated and have returned to
neurologic baseline or are neurologically stable (except for residual signs or
symptoms related to the CNS treatment).
3. Cytotoxic chemotherapy, surgery, radiotherapy or other targeted therapies and
checkpoint inhibitors (excluding nivolumab if not nivolumab treatment naive) within 3
weeks (4 weeks in cases of ramucirumab, mitomycin C, nitrosourea, lomustine; 1 week in
case of biopsy) prior to enrollment (adjuvant radiotherapy given to local area for
non-curative symptom relief is allowed until 2 weeks before enrollment).
4. Any other therapies including biological and approved therapies within 3 half-lives or
3 weeks whichever is longer and have not recovered from all toxicities from the
treatment.
5. Therapy with clinically significant systemic anticoagulant or anti thrombotic agents
within 7 days prior to enrollment that may prevent blood clotting and, in the
investigator's opinion, could place the participants at risk. Maximum dose of 325
milligram (mg)/day of aspirin is allowed.
6. History of bleeding diathesis or clinically significant bleeding within 14 days prior
to enrollment.
7. History of clinically significant thrombosis (bleeding or clotting disorder) within
the past 3 months prior to enrollment that, in the investigator's opinion, may place
the participant at risk of side effects from anti-angiogenesis products.
8. History of gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer
disease within the past 3 months prior to enrollment that, in the investigator's
opinion, may place the participant at risk of side effects from anti-angiogenesis
products.
9. Myocardial infarction or an unstable angina pectoris within 3 months prior to
enrollment.
10. Prior major surgery or fracture within 3 weeks prior to enrollment or presence of any
non-healing wound (procedures such as catheter placement are not considered to be
major).
11. Participation in any other interventional clinical trial, within 4 weeks prior to
enrollment or while participating in this study.
12. Previous treatment with apatinib.
13. Hypersensitivity to apatinib or components of its formulation.
14. History of uncontrolled hypertension ([HTN], blood pressure = 140/90 millimeters of
mercury [mmHg]) and change in anti hypertensive medication within 7 days prior to
enrollment) that is not well managed by medication and the risk of which may be
precipitated by VEGF inhibitor therapy.
15. History of severe adverse events including uncontrolled HTN or other common
anti-angiogenesis class drug effects that were related to ramucirumab or bevacizumab
discontinuation and/or may indicate a higher risk to the safety of the participant if
provided further anti-angiogenesis treatment, in the investigator's opinion.
16. History of symptomatic congestive heart failure (New York Heart Association III-IV),
symptomatic or poorly controlled cardiac arrhythmia, complete left bundle branch
block, bifascicular block, or any clinically significant ST segment and/or T-wave
abnormalities, QTcF>450 msec for males or QTcF > 470 msec for females prior to
enrollment.
17. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9, and
CYP2C19.
18. History of drug or alcohol abuse within past 5 years.
19. Known history of human immunodeficiency virus (HIV) infection or known acquired
immunodeficiency syndrome (AIDS).
20. Known history of positive tests for hepatitis B virus surface antigen (HBVsAg) or
hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
21. Pregnant or breast-feeding females.
22. Active bacterial infections.
23. Presence of substance abuse, medical, psychological, or social illness(es)that, in the
judgement of the investigator, may interfere with the participant's participation or
safety, or which may impact the objectives of the study.
24. History of clinically significant glomerulonephritis, biopsy-proven tubulointerstitial
nephritis, crystal nephropathy, or other renal insufficiencies.
25. Gastrointestinal malabsorption, or any other condition that in the opinion of the
investigator might affect the absorption of the study drug.
26. Grade 2 or greater toxicity from ongoing nivolumab treatment and irAE including
colitis and pneumonitis, if not nivolumab treatment naive.
27. Active autoimmune disease or a history of known autoimmune disease.
28. History of drug-induced interstitial pneumonitis or severe hypersensitivity to other
antibody therapies.
29. Known or underlying medical condition (for example, a condition associated with
diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the
administration of study drug hazardous to the participant or obscure the
interpretation of toxicity determination or adverse events.
30. Other conditions that, in the judgement of the investigator, contraindicate study
participation.
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