| Eligibility |
Inclusion Criteria:
- Written and signed informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
- Estimated life expectancy of =3 months.
- Histologically or cytologically confirmed recurrent or metastatic cervical cancer that
not appropriate for radical surgical resection and/or radical radiotherapy or
chemotherapy.
- For cohort A and B: The pathological types were squamous cell carcinoma,
adenocarcinoma, or adenosquamous cell carcinoma. No previous systematic treatment for
recurrent or metastatic cervical cancer.
- For cohort C: The pathological types were squamous cell carcinoma or adenosquamous
cell carcinoma. Subjects must have received platinum-containing dual-drug chemotherapy
combination with bevacizumab during or after the recurrence or metastasis phase and
have demonstrated radiologically confirmed disease progression during or after
treatment. Subjects will have no more than 2 lines of systemic therapy in the
recurrence or metastatic stages.
- Subjects must have at least one measurable lesion in accordance with RECIST v1.1.
- All subjects must provide archived or freshly acquired tumor tissue samples,
approximately 5 unstained FFPE pathological slides.
- Adequate organ function.
- Females of childbearing potential must have a negative blood pregnancy test within 7
days prior to the first administration. If having sex with an unsterilized male
partner, the subject must use an acceptable contraceptive method since screening and
must agree to continue using this contraceptive method for 120 days after the last
administration.
Exclusion Criteria:
- Subjects had clinically significant hydronephrosis that could not be relieved by
nephrostomy or urethral stenting, as determined by the investigator.
- Other active malignancies within 2 years prior to the first administration. Subjects
with locally curable tumors that appear to be cured, such as basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or
carcinoma in situ of the breast, were not excluded.
- Have received other study drugs or study devices within 4 weeks prior to the first
administration.
- Is participating in another clinical study, unless it is an observational,
non-interventional clinical study or a follow-up period for an interventional study.
- Subjects received systemic treatment with either proprietary Chinese drugs with
anti-tumor indications or herbal medicines with anti-tumor effects, or
immunomodulatory drugs (thymopeptide, interferon, interleukin) within 2 weeks prior to
the first administration.
- Had received the last course of systemic antitumor therapy within 4 weeks prior to the
first administration; Underwent major surgery within 3 weeks; Received non-specific
immunoregulatory system treatment within 2 weeks; Any herbal or proprietary Chinese
medicine with anti-tumor indications was received within 2 weeks.
- Have previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies,
anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such
as antibodies targeting ICOS, CD40, CD137, GITR, and Ox40 targets, etc.), immune cell
therapy, etc. Any treatment targeted at the immune mechanism of tumor.
- Subjects had an active autoimmune disease that required systemic treatment within 2
years prior to the first administration, or an autoimmune disease that was determined
by the investigator to be likely to recur or for which treatment was planned.
- Active or documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative
colitis, or chronic diarrhea).Inability to swallow, malabsorption syndrome, or
uncontrollable nausea, vomiting, diarrhea or other gastrointestinal disorders that can
seriously affect the administration and absorption of drug.
- Subjects requiring systemic treatment with glucocorticoids (> 10 mg/ day equivalent
dose of prednisone) or other immunosuppressive agents within 14 days prior to the
first administration.
- Known history of Immunodeficiency.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation.
- Underwent major surgery or severe trauma within 28 days prior to the first
administration; Underwent surgery to improve or reduce the risk of tumor complications
within 14 days prior to the first administration; Or have not fully recovered from
previous surgery. Significant surgery is planned within 30 days after the first
administration (as determined by the investigator).
- Medical history of gastrointestinal perforation, gastrointestinal fistula, and female
reproductive tract fistula within 6 months prior to the first administration; If the
perforation or fistula has been treated by excision or repair and the disease has been
recovered or remitted as determined by the investigator, admission is allowed.
- Known history of interstitial lung disease.
- Known history of active tuberculosis (TB).
- Serious infections within 4 weeks prior to the first administration, including but not
limited to complications requiring hospitalization, sepsis or severe pneumonia.
- An active infection requiring systemic therapy.
- Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA
exceeding 1000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects
with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <1000 IU/ mL)
, and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are
eligible only if the HCV RNA test results are negative.
- Known history of testing positive for human immunodeficiency virus (HIV).
- Metastases of the central nervous system, metastases of pia mater, spinal cord
compression, or pia mater disease confirmed by imaging or pathological examination.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage.
- Clinically active hemoptysis, active diverticulitis, peritoneal abscess, or
gastrointestinal obstruction.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria.
- Grade =2 peripheral nerve disease, defined according to the NCI CTCAE V5.0 standard.
- Receipt of live or attenuated vaccination within 30 days prior to the first
administration, or plan to receive live or attenuated vaccine during the study.
- Known history of serious hypersensitivity reaction to other monoclonal antibodies.
- Subjects with known contraindications to cisplatin/carboplatin, paclitaxel and
bevacizumab or a history of allergy/hypersensitivity to any of their components (refer
to the relevant drug label, not applicable for Cohort C, bevacizumab-related
contraindications and allergy to bevacizumab only to Cohort B).
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