Overview

Clinical Study of PD-1 Monoclonal Antibody SHR-1210 and Apatinib in Advanced NSCLC, Soft Tissue Sarcoma, and Uterine Cancer

Status:
Recruiting
Trial end date:
2022-03-31
Target enrollment:
0
Participant gender:
All
Summary
In this one-arm study, histologically or cytologically confirmed advanced NSCLC, uterine malignancies, and soft tissue sarcoma will be enrolled to investigate the efficacy and safety of PD-1 monoclonal antibody SHR-1210 and apatinib, at the same time, peripheral circulating blood tumor cells (CTC) detection and CTC-based PD-L1 antibody immunofluorescence detection will be performed.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hunan Cancer Hospital
Collaborator:
Jiangsu HengRui Medicine Co., Ltd.
Treatments:
Antibodies
Antibodies, Monoclonal
Apatinib
Immune Checkpoint Inhibitors
Criteria
Inclusion Criteria:

1. Age 18-70 years, both men and women (Uterine cancer limited to women);

2. NSCLC: Pathologically confirmed advanced (IIIB, stage IV) NSCLC with at least 1
measurable lesion that meets the RECIST v1.1 standard without local treatment, of
which stage IIIb patients are incapable, unsuitable for surgery or radical
radiotherapy, NSCLC patients have failed at least the first-line standard treatment or
refused to receive standard treatment, or chemotherapy intolerance, Among them,
patients with sensitive gene mutations must fail after TKI treatment (patients who
have failed first-line or second-line treatment may participate in this study),
Patients with EGFR and ALK mutations must undergo EGFR and ALK inhibitor treatment
failure and EGFR T790M mutation negative, for EGFR T790M-positive patients,
third-generation EGFR TKI treatment fails.

3. Soft tissue sarcoma: Patients with distant metastasis or locally advanced disease who
have previously failed chemotherapy or sensitive recurrence or metastasis to soft
tissue sarcoma. Subjects who have judged by the investigator to be unsuitable for
surgical treatment (including amputation) of soft tissue sarcomas (diagnosed
pathologically or cytologically, but excluding gastrointestinal stromal tumors,
chondrocyte-bone tumors, embryonic/acinar rhabdomyosarcoma, Juventus Sarcoma,
extensive distant metastatic soft tissue tumors such as keloid cutaneous fibrosarcoma
and inflammatory myofibroblastic sarcoma, malignant peripheral nerve sheath tumor,
keloid cutaneous fibrosarcoma, inflammatory myofibroblastic sarcoma, malignant
interstitial Dermatoma) (priority consideration: synovial sarcoma, undifferentiated
multiline sarcoma, dedifferentiated liposarcoma), and measurable lesions that meet the
RECIST 1.1 standard.

4. Uterine cancer: Pathologically confirmed uterine cancer, including cervical cancer
(squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma), endometrial
cancer, and uterine sarcoma, at least one measurable lesion that meets RECIST 1.1
criteria, recurrence/Persons with persistent cervical cancer, endometrial cancer, and
uterine sarcoma cannot be cured by surgery and/or radiotherapy, have received at least
a first-line treatment for advanced (stage IVB), recurrent/persistent cervical cancer,
endometrial cancer, uterine sarcoma Systemic chemotherapy patients (qualified to
participate in this study after the progress of first-line chemotherapy).

5. All acute toxicity caused by previous antitumor treatments were alleviated to level
0-1 (according to NCI CTCAE version 4.03) or to the level specified by the enrollment/
exclusion criteria 1 day before the first dose except for subjects whose toxicity does
not pose a safety risk);

6. Able to provide tumor samples (at least 20 unstained tumor samples or fresh tissue
specimens embedded in formalin-fixed paraffin within six months, 4ml of peripheral
blood samples before treatment and each effect evaluation);

7. ECOG score: 0-1, patients with soft tissue sarcoma amputation can be relaxed to 2
points;

8. Expected survival ≥ 12 weeks;

9. The function of important organs meets the following requirements (excluding the use
of any blood components and cell growth factors during screening);

1. Absolute neutrophil count ≥1.5 × 109 / L;

2. platelets ≥100 × 109/L;

3. Hemoglobin ≥9g/dL;

4. serum albumin ≥3g/dL;

5. total bilirubin ≤ 1.5ULN;

6. ALT and AST ≤1.5ULN;

7. AKP ≤ 2.5ULN;

8. Serum creatinine ≤ 1.5ULN or creatinine clearance ≥ 60mL/min;

10. Non-surgical sterilization female patients;

11. Participants volunteered to participate in the study, signed informed consent, good
compliance, and cooperated with the follow-up.

Exclusion Criteria:

1. Participants who had any active autoimmune disease or a history of autoimmune disease
(such as the following, but not limited to: autoimmune hepatitis, interstitial
pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis,
nephritis , Hyperthyroidism, decreased thyroid function; subjects with vitiligo or
childhood asthma has completely resolved, adults can be included without any
intervention; subjects with bronchodilators for medical intervention can not be
included in asthma;

2. Participants who were treated with immunosuppressive agents, or systemic or absorbable
local hormones for immunosuppressive purposes (dose>10mg/day, prednisone or other
curative hormones), and continued to use it within 2 weeks before enrollment;

3. Excessive allergic reactions to other monoclonal antibodies;

4. Participants who had clinical symptoms of central nervous system metastases (such as
brain edema, require hormonal intervention, or progress of brain metastases).
Participants who had previously received brain or meningeal metastasis treatment, such
as clinical stability (MRI) that has been maintained for at least 1 month, and have
stopped systemic hormonal therapy (dose> 10 mg / day prednisone or other therapeutic
hormone) can be included;

5. Imaging (CT or MRI) showed that the tumor invades or demarcates large blood vessels.

6. Imaging (CT or MRI) showed obvious hollow or necrotic tumors in the lungs; those with
marginal adenocarcinoma with cavities can be considered after discussion with the
clinician.

7. Participants who had high blood pressure and cannot be well controlled with
antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood
pressure ≥90 mmHg).

8. Participants who had poorly controlled clinical symptoms or diseases of the heart,
such as: (1) heart failure above NYHA 2 (2) unstable angina pectoris (3) myocardial
infarction within 1 year (4) clinically significant supraventricular Sexual
arrhythmias require treatment or intervention.

9. Participants who had abnormal blood coagulation (PT> 16s, APTT> 43s, TT> 21s, Fbg <2g
/ L), bleeding tendency or receiving thrombolytic or anticoagulation;

10. Urine routine indicates urinary protein ≥ ++, or confirms that 24-hour urine protein
is ≥1.0 g;

11. Participants who previously received radiotherapy, chemotherapy, hormone therapy,
surgery or molecular targeted therapy. After treatment is completed (last dose),
subjects less than 4 weeks before study medication (or 5 drug half-life, whichever is
longer) Patients who did not recover from adverse events (excluding hair loss) from
previous treatment to ≤CTCAE 1 degree;

12. Clinically ascites or pleural effusion requiring therapeutic puncture or drainage;

13. Participants who had obvious cough blood in the first 2 months of randomization, or a
day with hemoptysis of half teaspoon (2.5ml) or more;

14. Participants who had clinically significant bleeding symptoms or have a clear bleeding
tendency within the first 3 months of randomization, such as gastrointestinal
bleeding, hemorrhagic gastric ulcer, fecal occult blood at baseline and above, or have
vasculitis;

15. Participants who had arterial/venous thrombotic events such as cerebrovascular
accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral
infarction), deep vein thrombosis and pulmonary embolism occurred within the first 6
months;

16. Participants who had known hereditary or acquired bleeding and thrombotic tendency (eg
hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.);

17. Participants who had an active infection or an unexplained fever during the screening
period before the first dose> 38.5 degrees;

18. Patients with past and current objective evidence of pulmonary fibrosis, interstitial
pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe
impairment of lung function, etc;

19. Participants who had congenital or acquired immune deficiency (such as HIV-infected
persons), or positive for syphilis spiral antibodies, or active hepatitis (HBV
reference: HBsAg positive, and HBV DNA detection exceeds the upper limit of normal
values; (And the HCV virus titer detection value exceeds the upper limit of normal
value);

20. Participants who have used other drugs in clinical trials within 4 weeks before the
first use;

21. Participants has previous or concurrent other malignancies (except cured skin basal
cell carcinoma and cervical carcinoma in situ);

22. Participants may receive other systemic anti-tumor treatments during the study;

23. Participants with bone metastases who had received palliative radiation therapy within
4 weeks before participating in the study;

24. Participants who have previously received other PD-1 antibody treatments or other
immunotherapy against PD-1/PD-L1 or VEGFR single-target/multi-target inhibitors, such
as Sunitinib, Sorafeni, Bevacizumab, Anlotinib, Famitinib, Apatinib, and Reginafinib
(in advanced NSCLC, there is no need to exclude previous VEGFR single / multitarget
inhibitor Patients treated, but need to be discontinued for more than 4 weeks);

25. Live vaccine may be given less than 4 weeks before study medication or possibly during
the study;

26. According to the researcher's judgment, Participants has other factors that may lead
to the termination of the study. Serious diseases (including mental illness) require
combined treatment. There are serious laboratory abnormalities, accompanied by family
or social factors. To the safety of the subject, or the collection of information and
samples;