| Eligibility |
Inclusion Criteria:
1. Fully understand and voluntarily sign the informed consent form and agree to receive
treatment, examination and follow-up as required by the study protocol;
2. Age = 18, < 80 years, male or female;
3. ECOG score =2;
4. unresectable or recurrent metastatic FH-deficient renal cell carcinoma not previously
treated with systemic antitumor therapy, as confirmed by histology. Prior cytokine
therapy is allowed;
5. At least 1 measurable tumor lesion according to RECIST 1.1 criteria. The lesion that
has received prior radiotherapy and progressed again is allowed as a target lesion;
6. agree to provide blood and urine samples and previous archived or fresh tumor tissue
samples.
7. Demonstrates adequate organ function.
8. Female subjects of childbearing potential must have a negative serum pregnancy test
result within 7 days prior to the first dose. participants of childbearing potential
must be willing to use an adequate method of contraception for the course of the study
through 180 days after the last dose of study drug.
Exclusion Criteria:
1. Prior treatment with agents targeting VEGF, VEGFR, or mTOR, including but not limited
to sunitinib, axitinib, pazopanib, sorafenib, cabozantinib, lenvatinib, bevacizumab,
anlotinib, or everolimus;
2. Prior treatment with anti-PD-1, PD-L1 or CTLA-4 antibodies;
3. Participants who are using other investigational agents or who had received
investigational drugs <=4 weeks prior to study treatment start;
4. Received major surgery or is recovering from surgery (as judged by the investigator)
within 4 weeks;
5. Received Chinese herbal or proprietary Chinese medicine preparation with an antitumor
indication within 2 weeks;
6. Requirement of adrenocorticosteroids (>10 mg prednisone or equivalent daily) or other
immunosuppressive systemic therapy within 2 week; inhalation of >10 mg prednisone or
equivalent daily, but without active autoimmune disease may participate in this study;
7. History of organ transplantation or conditions requiring long-term
adrenocorticosteroid or immunosuppressive therapy
8. Hypothyroidism, adrenal or pituitary gland function that can be controlled with
hormone replacement therapy, type I diabetes mellitus, psoriasis or vitiligo that do
not require systemic therapy may be enrolled in the study;
9. Didn't recover from prior antineoplastic therapy, grade 0 to 1 as defined by NCI-CTCAE
5.0 (except alopecia), or levels specified in the inclusion/exclusion criteria.
Irreversible toxicity that is not expected to be exacerbated by the study drug can be
enrolled;
10. The presence of other malignancies that have progressed or require treatment within 5
years (excluding basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, superficial bladder cancer or cured carcinoma in situ, such as carcinoma in situ
of the breast, prostate cancer: subjects with limited low-risk prostate cancer (= T2a,
Gleason score = 6, PSA < 10ng/ml) who have received radical treatment and no PSA
biochemical (those with recurrence may participate in this study);
11. History of active central nervous system (CNS) metastases or baseline phase imaging
showing CNS metastases within 30 days prior to the first dose. Subjects with prior
surgical or radiation treatment for brain or meningeal metastases who have maintained
clinical stability for = 3 months by screening and have discontinued systemic hormone
therapy (dose > 10 mg/day of prednisone or other equivalent hormone) for > 4 weeks may
be enrolled. Subjects may be enrolled in this study if the subject's CNS metastases
can be treated to meet the requirements of the enrollment criteria and if the
subject's CNS symptoms have returned to = grade 1 for at least 2 weeks prior to
enrollment (except for residual signs or symptoms related to CNS treatment);
12. Poorly controlled hypertension: SBP = 150 mmHg and/or DBP = 90 mmHg;
13. Any one or more of the following cardiovascular disease states within the last 6
months: myocardial infarction; unstable angina; endoluminal angioplasty or coronary
stenting; coronary/peripheral artery bypass graft; NYHA cardiac function class 3-4;
congestive heart failure; cerebrovascular accident including transient ischemic
attack;
14. Heart rate corrected QT interval (QTc) = 480 ms;
15. History of active bleeding or other severe bleeding within 1 month;
16. Deep vein thrombosis or pulmonary embolism within 6 months;
17. Arterial embolism within the last 12 months;
18. Clinically significant gastrointestinal abnormalities, including: malabsorption, total
gastrectomy, or any condition that may interfere with the absorption of oral
medications; active ulcers treated within 6 months; active gastrointestinal bleeding
(vomiting blood, blood in stool, or black stool) within 3 months by endoscopy;
metastatic lesions in the gastrointestinal tract suspected of bleeding, inflammatory
bowel disease, ulcerative colitis Gastrointestinal perforation or other
gastrointestinal disorders that increase the risk of perforation;
19. The presence of (non-infectious) pneumonia/interstitial lung disease requiring
adrenocorticosteroid therapy, either previously or currently
20. Presence of active infection requiring systemic therapy, presence of human
immunodeficiency virus (HIV) infection (known HIV antibody positivity), presence of
active HBV infection (HBsAg positive, or HBcAb positive but HBsAg negative, additional
DNA quantification is required and results that do not exceed the upper limit of
normal laboratory values can be enrolled), presence of active HCV infection (previous
HCV infected patients with negative HCV RNA test results during the screening period
can be enrolled);
21. Live virus vaccinations within the last 1 month, including but not limited to mumps,
rubella, measles, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccines,
excluding inactivated virus vaccines;
22. A history of severe drug allergy, including but not limited to antibody drugs and
small molecule targeted drugs;
23. Known psychiatric illness or history of substance abuse;
24. Presence of unhealed wounds;
25. The presence of any medical history or current evidence of disease, treatment or
laboratory abnormality that, in the investigator's judgment, could confound the
results of the trial, interfere with the subject's participation in the full trial, or
is not in the subject's best interest to participate in the trial.
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