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

Non-Squamous Non-Small Cell Neoplasm of Lung Clinical Trial

— DOMAJOR  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03912389
• Other study ID #: BCD-100-3
• Status: Recruiting
• Phase: Phase 3
• Start date: June 1, 2019
• Est. completion date: December 2023

Study information

• Verified date: September 2020
• Source: Biocad
• Contact: Fedor B Krykov, MD, PhD
• Phone: +7-(812)-380-49-33
• Email: biocad[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 292
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ? 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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non-Squamous Non-Small Cell Neoplasm of Lung

Intervention

Biological:
• BCD-100
Anti-PD-1 monoclonal antibody, IV infusion

Drug:
• Pemetrexed
IV infusion
• Cisplatin (or carboplatin)
IV infusion

Other:
• Placebo
IV infusion

Locations

Country	Name	City	State
Czechia	Regional Hospital Liberec	Liberec
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Ostrava	Ostrava
Czechia	Multiscan Pardubice - Radiology Center	Pardubice
Georgia	High technology Hospital Medcenter	Batumi
Georgia	Acad. F.Todua Medical center "Research institute of Clinical Medicine"	Tbilisi
Georgia	High Technology Medical Centre, University Clinic	Tbilisi
Georgia	Institute for Personalized Medicine Ltd.	Tbilisi
Georgia	LEPL First University Clinic of Tbilisi State Medical University	Tbilisi
Hungary	National Korányi Institute of Pulmonology IV. Pulmonology	Budapest
Hungary	Semmelweis University Pulmonology Clinic	Budapest
Hungary	Mátra Health Institution Pulmonology	Mátraháza
Romania	S.C Radiotherapy Center Cluj S.R.L	Cluj
Romania	S.C Medisprof S.R.L	Cluj-Napoca
Romania	"Sfantul Nectarie" Oncology Center SRL	Craiova
Romania	S.C Oncolab S.R.L	Craiova
Romania	S.C Pelican Impex S.R.L	Oradea
Romania	Emergency Clinical Municipal Hospital Timisoara - Medical Oncology Clinic	Timisoara
Romania	S.C Oncocenter Clinical Oncology S.R.L	Timisoara
Romania	S.C Oncomed S.R.L	Timisoara
Romania	S.C Salvosan Ciobanca S.R.	Zalau
Russian Federation	Arkhangelsk Clinical Oncology Dispensary	Arkhangel'sk
Russian Federation	City Hospital No. 5	Barnaul
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky	Krasnoyarsk
Russian Federation	Moscow City Oncology Hospital No. 62	Moscow
Russian Federation	Clinical Oncology Dispensary	Omsk
Russian Federation	LLC "New Clinic"	Pyatigorsk
Russian Federation	AV Medical Group	Saint Petersburg
Russian Federation	LLC BioEk	Saint Petersburg
Russian Federation	Regional Clinical Oncology Hospital	Yaroslavl
Slovakia	St. Jacob's Hospital	Bardejov
Slovakia	Eastern Slovak Oncology Institute	Košice
Slovakia	Hospital Komarno a.s.	Komarno
Slovakia	Faculty Hospital with Policlinic of Stefan Kukura	Michalovce
Slovakia	Faculty Hospital with Policlinic	Nove Zamky
Slovakia	Outpatient Oncology Clinic	Partizanske
Slovakia	Faculty Hospital of J.A. Reiman	Presov

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Czechia,  Georgia,  Hungary,  Romania,  Russian Federation,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	The time from the date of randomization until death	3 years
Secondary	Progression-Free Survival (PFS)	The time from the date of randomization until progression of disease according to RECIST 1.1 and iRECIST or death	1 year
Secondary	Overall Response Rate (ORR)	The percentage of the participants who have a Complete Response or a Partial Response as assessed by a blind independent central reviewer per RECIST 1.1 and iRECIST	1 year
Secondary	Disease Control Rate (DCR)	The percentage of the participants who have a Complete Response, a Partial Response or a Stable Disease as assessed by a blind independent central reviewer per RECIST 1.1 and iRECIST	1 year
Secondary	Time to Response (TTR)	TTR will be calculated from the randomization date	1 year
Secondary	Duration of Response (DOR)	DOR will be calculated from the moment of registration of response till event (disease progression or death)	1 year