Clinical trial NCT03912389: Efficacy and Safety of BCD-100 (Anti-PD-1) in Combination With Platinum-Based Chemotherapy as First Line Treatment in Patients With Advanced Non-Squamous NSCLC
Official title: International Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial Evaluating Efficacy and Safety Of BCD-100 in Combination With Pemetrexed+Cisplatin/Carboplatin Compared to Placebo in Combination With Pemetrexed+Cisplatin/Carboplatin as First-Line Treatment of Subjects With Advanced Non-squamous Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non-Squamous Non-Small Cell Neoplasm of Lung
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2019-04-11
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, multicenter, double-blind placebo-controlled phase 3 study of efficacy and safety of BCD-100 in combination with pemetrexed+cisplatin/carboplatin compared to placebo in combination with pemetrexed+cisplatin/carboplatin in subjects with previously untreated metastatic non-squamous NSCLC. The main hypothesis of the study is that BCD-100 in combination with chemotherapy prolongs OS compared to placebo with chemotherapy.


Eligibility criteria: Inclusion Criteria:

1. Subject has voluntarily agreed to participate by giving written informed consent for the trial;
2. Patients ≥ 18 years of age on day of signing informed consent;
3. Previously untreated patients with histologically-confirmed stage IV (M1a/M1b/M1c- AJCC 8th edition) non-squamous NSCLC;
4. Has not received prior systemic treatment for metastatic NSCLC;
5. The time from the completion of previous adjuvant/neoadjuvant treatment to metastatic disease development is no less than 12 months;
6. Has a life expectancy of at least 12 weeks;
7. Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
8. Has adequate organ function as defined by hematological laboratory values (absolute neutrophil count ≥1.500/mcL, platelets ≥100.000/mcL, hemoglobin ≥9 g/dL ), renal laboratory values (serum creatinine or calculated creatinine clearance \<1.5xULN or ≥60 mL/min for subjects with creatinine levels\>1.5x institutional ULN), and hepatic laboratory values (serum total bilirubin \<1.5xULN, AST and ALT ≤2.5xULN, alkaline phosphatase \<2.5xULN);
9. Agreement to newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for determination of PD-L1 status prior to randomization (if obtaining of new sample is contraindicated or puts subject at unacceptable risks, then archival tumor tissue sample must be available)
10. Measurable disease according to CT scan (RECIST 1.1 criteria) , confirmed by the local assessment;
11. For subjects of childbearing potential: agreement to remain abstinent (refrain from heterosexual inter-course) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 6 months after administration of the last dose of study drug; and 6 months after the last dose of platinum-based chemotherapy, whichever is later. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes, and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include but are not limited to bilateral tubal ligation and/or occlusion, male sterilization, and intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

1. Has predominantly squamous cell histology NSCLC; Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible.
2. Presence of EGFR mutation or ALK translocation;
3. Has received prior systemic cytotoxic chemotherapy/chemoradiotherapy for metastatic disease;
4. Has received antineoplastic therapy with targeted or immunotherapeutic drugs (including but not limited to EGFR inhibitors \[e.g., erlotinib, gefitinib, cetuximab\], ALK inhibitors, PD-1/PD-L1/PD-L2/CTLA4, VEGF/VEGFR inhibitors) or it is expected to require any other form of antineoplastic therapy while on study;
5. Completed radiation therapy within 14 days before the first dose of the study drug;
6. Received a live-virus vaccination within 30 days prior to the first study drug administration;
7. Current treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study;
8. Had major surgery less than 28 days prior to the first dose of the study drug;
9. Evidence of severe or concomitant diseases/life-threatening complications of the main condition (including but not limited to massive pleural, pericardial, or peritoneal effusion that requires medical intervention , pulmonary lymphangitis, hemorrhage, organ perforation) at the signing of the informed consent;
10. Concomitant diseases or conditions which pose a risk of AE development during study treatment:

    1. uncontrolled hypertension, defined as systolic \> 150 mm Hg or diastolic \> 90 mm Hg; define diagnosis of hypertension
    2. stable angina functional class III-IV;
    3. unstable angina or myocardial infarction less than 6 months prior to randomization;
    4. NYHA Grade III-IV congestive heart failure;
    5. serious cardiac arrhythmia requiring medication (subjects with asymptomatic atrial fibrillation can be enrolled if controlled ventricular rate);
    6. atopic asthma, Stage III-IV COPD, angioedema;
    7. severe respiratory failure;
    8. any other diseases which pose unacceptable risk of AE development during study treatment in Investigator's opinion;
11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis ;
12. Active or known or suspected autoimmune disease (subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll).
13. Has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis;
14. Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary;
15. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications in past 2 years;
16. Is unable or unwilling to take folic acid or vitamin B12 supplementation;
17. Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 2 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers;
18. Pre-existing clinically significant (≥ grade 2) peripheral neuropathy or hearing impairment;
19. Any conditions or circumstances that limit subject's ability to comply with protocol requirements;
20. Active hepatitis B, hepatitis С or HIV in anamnesis;
21. Acute infection or reactivation of chronic infection or systemic antibiotics use less than 14 days prior to first dose of the study drug; Severe infections within 28 days prior to the first study drug administration.
22. Significant adverse reactions of previous therapy excluding chronic and/or irreversible events which cannot affect study drug safety evaluation (e.g. alopecia);
23. Known hypersensitivity or allergy to drugs containing Chinese hamster (CHO) ovary cells or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, to pemetrexed, carboplatin, cisplatin, BCD-100 or any of their excipients;
24. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 1 year
measure: Overall Response Rate (ORR)
timeFrame: 1 year
measure: Disease Control Rate (DCR)
timeFrame: 1 year
measure: Time to Response (TTR)
timeFrame: 1 year
measure: Duration of Response (DOR)
timeFrame: 1 year
Other outcomes:
Locations:
city: Liberec
country: Czechia
facility: Regional Hospital Liberec
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Pardubice
country: Czechia
facility: Multiscan Pardubice - Radiology Center
city: Batumi
country: Georgia
facility: High technology Hospital Medcenter
city: Tbilisi
country: Georgia
facility: Acad. F.Todua Medical center "Research institute of Clinical Medicine"
city: Tbilisi
country: Georgia
facility: High Technology Medical Centre, University Clinic
city: Tbilisi
country: Georgia
facility: Institute for Personalized Medicine Ltd.
city: Tbilisi
country: Georgia
facility: LEPL First University Clinic of Tbilisi State Medical University
city: Budapest
country: Hungary
facility: National Korányi Institute of Pulmonology IV. Pulmonology
city: Budapest
country: Hungary
facility: Semmelweis University Pulmonology Clinic
city: Mátraháza
country: Hungary
facility: Mátra Health Institution Pulmonology
city: Cluj-Napoca
country: Romania
facility: S.C Medisprof S.R.L
city: Cluj
country: Romania
facility: S.C Radiotherapy Center Cluj S.R.L
city: Craiova
country: Romania
facility: "Sfantul Nectarie" Oncology Center SRL
city: Craiova
country: Romania
facility: S.C Oncolab S.R.L
city: Oradea
country: Romania
facility: S.C Pelican Impex S.R.L
city: Timisoara
country: Romania
facility: Emergency Clinical Municipal Hospital Timisoara - Medical Oncology Clinic
city: Timisoara
country: Romania
facility: S.C Oncocenter Clinical Oncology S.R.L
city: Timisoara
country: Romania
facility: S.C Oncomed S.R.L
city: Zalau
country: Romania
facility: S.C Salvosan Ciobanca S.R.
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Clinical Oncology Dispensary
city: Barnaul
country: Russian Federation
facility: City Hospital No. 5
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital No. 62
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: LLC "New Clinic"
city: Saint Petersburg
country: Russian Federation
facility: AV Medical Group
city: Saint Petersburg
country: Russian Federation
facility: LLC BioEk
city: Yaroslavl
country: Russian Federation
facility: Regional Clinical Oncology Hospital
city: Bardejov
country: Slovakia
facility: St. Jacob's Hospital
city: Komarno
country: Slovakia
facility: Hospital Komarno a.s.
city: Košice
country: Slovakia
facility: Eastern Slovak Oncology Institute
city: Michalovce
country: Slovakia
facility: Faculty Hospital with Policlinic of Stefan Kukura
city: Nove Zamky
country: Slovakia
facility: Faculty Hospital with Policlinic
city: Partizanske
country: Slovakia
facility: Outpatient Oncology Clinic
city: Presov
country: Slovakia
facility: Faculty Hospital of J.A. Reiman
Study officials:
affiliation: Director of Clinical Development Department, BIOCAD
name: Yulia N Linkova, MD, PhD
role: STUDY_DIRECTOR
References: