Efficacy and Safety of BCD-100 (Anti-PD-1) in Combination With Platinum-Based Chemotherapy With and Without Bevacizumab as First-Line Treatment of Subjects With Advanced Cervical Cancer (FERMATA)

Inclusion Criteria:

1. Signing an IRB/EC-approved informed consent

2. Females ≥ 18 years of age on day of signing informed consent

3. Histologically confirmed squamous carcinoma of the cervix

4. Progressing thru or recurrent disease treated for curative intent or primarymetastatic cervical cancer stage FIGO IVB

5. Agreement to newly obtained core or excisional biopsy of a tumor lesion not previouslyirradiated for determination of PD-L1 status prior to randomization (using archivalbiopsy material is only acceptable in subjects in whom obtaining a new sample iscontraindicated)

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or to use a contraceptive method with a failure rate of < 1%per year from the moment of signing informed consent, during the treatment period andat least 6 months after administration of the last dose of study drug. A woman isconsidered to be of childbearing potential if she is postmenarcheal, has not reached apostmenopausal state (≥ 12 continuous months of amenorrhea with no identified causeother than menopause), and has not undergone surgical sterilization (removal ofovaries, fallopian tubes, and/or uterus). Examples of contraceptive methods with afailure rate of < 1% per year include but are not limited to bilateral tubal ligationand/or occlusion, male sterilization, and intrauterine devices. The reliability ofsexual abstinence should be evaluated in relation to the duration of the clinicalstudy and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g.,calendar, ovulation, symptothermal, or postovulation methods) is not acceptable methodof contraception.

Exclusion Criteria:

1. Indications for potentially curative treatment (surgery or radiation therapy)

2. Prior systemic treatment for recurrent, secondarily progressive or initiallymetastatic disease

3. Previous use of chemotherapy other than initial treatment for curative intent (e.g.chemotherapy used concurrently with radiation therapy, neoadjuvant or consolidationchemotherapy cycles before radiotherapy or 2 chemotherapy cycles after completion ofchemoradiotherapy are allowed)

4. Contraindications to cisplatin, carboplatin, paclitaxel, or bevacizumab

5. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.Participants with known brain metastases may participate provided that the brainmetastases have been previously treated with radiotherapy or surgery only and areradiographically stable

6. Concomitant diseases or conditions which pose a risk of AE development during studytreatment:

7. uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mmHg;

8. stable angina functional class III-IV;

9. unstable angina or myocardial infarction less than 6 months prior torandomization;

10. NYHA Grade III-IV congestive heart failure;

11. serious cardiac arrhythmia requiring medication (subjects with asymptomaticatrial fibrillation can be enrolled if controlled ventricular rate);

12. atopic asthma, Stage III-IV COPD, angioedema;

13. severe respiratory failure;

14. any other diseases which pose unacceptable risk of AE development during studytreatment in Investigator's opinion.

15. Active or known or suspected autoimmune disease (subjects with Type 1 diabetesmellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted toenroll).

16. Condition requiring systemic treatment with either corticosteroids or otherimmunosuppressive medications within 14 days prior to randomization.

17. History of (non-infectious) pneumonitis that required corticosteroids or currentpneumonitis

18. Neutrophils <1500/mcl or platelets <100 000/mcl or hemoglobin <90 g/l.

19. Creatinine ≥ 1.5 x UNL.

20. Bilirubin ≥ 1.5 x UNL (excluding Gilbert's syndrome if bilirubin < 50 µmol/l) orAST/ALT ≥ 3 x UNL (excluding subjects with liver metastases if AST/ALT < 5 x UNL) oralkaline phosphatase ≥ 2.5 x UNL.

21. Chemotherapy or radiation therapy less than 28 days prior to randomization.

22. Major surgery procedure less than 28 days prior to randomization.

23. Previous use of PD-1/PD-L1/PD-L2 agent or another agent directed to stimulatory orco-inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137).

24. Previous use of VEGF/VEGFR inhibitors, including bevacizumab, ramucirumab, afliberceptand tyrosine kinase inhibitors.

25. Prior invasive malignancy with any evidence of disease within the last 3 years.Subjects with non-melanoma skin cancer or carcinoma in situ (e.g. breast cancer) whohave undergone potentially curative therapy are not excluded.

26. Pre-existing clinically significant (≥ grade 2) peripheral neuropathy or hearingimpairment

27. Any conditions or circumstances that limit subject's ability to comply with protocolrequirements

28. Active hepatitis B, active hepatitis С or history of positive HIV.

29. Active infection requiring therapy or systemic antibiotics use less than 14 days priorto enrollment. Severe infections within 28 days prior to first study drugadministration.

30. Administration of a live vaccine within 28 days prior to enrollment

31. Current using of another investigational device or drug study, or less than 30 dayssince ending of using of another investigational device or drug study

32. Life expectancy less than 12 weeks

33. Significant adverse events (AE) of previous therapy excluding chronic and/orirreversible events which cannot affect study drug safety evaluation (e.g. alopecia)

34. Known hypersensitivity or allergy to paclitaxel, cisplatin, carboplatin, bevacizumab,BCD-100 or any of their excipients. Known hypersensitivity or allergy to drugs derivedfrom Chinese hamster (CHO) ovary cells or history of severe allergic, anaphylactic, orother hypersensitivity reactions to chimeric or humanized antibodies or fusionproteins.

35. Pregnancy or breast-feeding