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 (DOMAJOR)

September 15, 2020 updated by: Biocad

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)

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

292

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fedor B Krykov, MD, PhD
  • Phone Number: +7-(812)-380-49-33
  • Email: biocad@biocad.ru

Study Contact Backup

  • Name: Sergey N Fogt, MD, PhD
  • Phone Number: +7-(812)-380-49-33
  • Email: biocad@biocad.ru

Study Locations

      • Liberec, Czechia
        • Recruiting
        • Regional Hospital Liberec
        • Contact:
          • Marek Sochor, MD
      • Olomouc, Czechia
        • Recruiting
        • University Hospital Olomouc
        • Contact:
          • Bohuslav Melichar, MD, PhD
      • Ostrava, Czechia
        • Recruiting
        • University Hospital Ostrava
        • Contact:
          • Tomas Bartek, MD
      • Pardubice, Czechia
        • Recruiting
        • Multiscan Pardubice - Radiology Center
        • Contact:
          • Jaroslav Vanasek, MD, PhD
      • Batumi, Georgia
        • Recruiting
        • High Technology Hospital Medcenter
        • Contact:
          • Tamta Makharadze, MD
      • Tbilisi, Georgia
        • Recruiting
        • Acad. F.Todua Medical center "Research institute of Clinical Medicine"
        • Contact:
          • Tamar Melkadze, MD
      • Tbilisi, Georgia
        • Recruiting
        • High Technology Medical Centre, University Clinic
        • Contact:
          • Miranda Gogishvili, MD
      • Tbilisi, Georgia
        • Recruiting
        • Institute for Personalized Medicine Ltd.
        • Contact:
          • Alexandre Tavartkiladze, MD, PhD
      • Tbilisi, Georgia
        • Recruiting
        • LEPL First University Clinic of Tbilisi State Medical University
        • Contact:
          • Nana Chikhladze, MD
      • Budapest, Hungary
        • Recruiting
        • National Korányi Institute of Pulmonology IV. Pulmonology
        • Contact:
          • Krisztina BOGOS, MD
      • Budapest, Hungary
        • Recruiting
        • Semmelweis University Pulmonology Clinic
        • Contact:
          • Veronika MÜLLER, MD, PhD
      • Mátraháza, Hungary
        • Recruiting
        • Mátra Health Institution Pulmonology
        • Contact:
          • László URBÁN, MD, PhD
      • Cluj, Romania
        • Recruiting
        • S.C Radiotherapy Center Cluj S.R.L
        • Contact:
          • Manolescu A Alexandru, MD
      • Cluj-Napoca, Romania
        • Recruiting
        • S.C Medisprof S.R.L
        • Contact:
          • Udrea A Anghel, MD
      • Craiova, Romania
        • Recruiting
        • "Sfantul Nectarie" Oncology Center SRL
        • Contact:
          • Schenker Michael, MD
      • Craiova, Romania
        • Recruiting
        • S.C Oncolab S.R.L
        • Contact:
          • Lungulescu Stefan, MD
      • Oradea, Romania
        • Recruiting
        • S.C Pelican Impex S.R.L
        • Contact:
          • Puscas I Adriana, MD
      • Timisoara, Romania
        • Recruiting
        • Emergency Clinical Municipal Hospital Timisoara - Medical Oncology Clinic
        • Contact:
          • Curescu Petra, MD
      • Timisoara, Romania
        • Recruiting
        • S.C Oncocenter Clinical Oncology S.R.L
        • Contact:
          • Scheusan R Ioana, MD
      • Timisoara, Romania
        • Recruiting
        • S.C Oncomed S.R.L
        • Contact:
          • Segarceanu N Alina, MD
      • Zalau, Romania
        • Recruiting
        • S.C Salvosan Ciobanca S.R.
        • Contact:
          • Papp Margareta, MD
      • Arkhangel'sk, Russian Federation
        • Recruiting
        • Arkhangelsk Clinical Oncology Dispensary
        • Contact:
          • Marina N Nechaeva, MD
      • Barnaul, Russian Federation
        • Recruiting
        • City Hospital No. 5
        • Contact:
          • Denis A Tancyirev, MD
      • Krasnoyarsk, Russian Federation
        • Recruiting
        • Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky
        • Contact:
          • Ruslan A Zukov, MD, PhD
      • Moscow, Russian Federation
        • Recruiting
        • Moscow City Oncology Hospital No. 62
        • Contact:
          • Daniil L Stroyakovsky, MD, PhD
      • Omsk, Russian Federation
        • Recruiting
        • Clinical Oncology Dispensary
        • Contact:
          • Mikhail V Dvorkin, MD, PhD
      • Pyatigorsk, Russian Federation
        • Recruiting
        • LLC "New Clinic"
        • Contact:
          • Valery M Chistyakov, MD, PhD
      • Saint Petersburg, Russian Federation
        • Recruiting
        • AV Medical Group
        • Contact:
          • Timur T Andabekov, MD, PhD
      • Saint Petersburg, Russian Federation
        • Recruiting
        • LLC BioEk
        • Contact:
          • Svetlana Odintsova, MD
          • Phone Number: +78129452232
      • Yaroslavl, Russian Federation
        • Recruiting
        • Regional Clinical Oncology Hospital
        • Contact:
          • Nikolay V Kislov, MD, PhD
      • Bardejov, Slovakia
        • Recruiting
        • St. Jacob's Hospital
        • Contact:
          • Jozef Chovanec, MD
      • Komarno, Slovakia
        • Recruiting
        • Hospital Komarno a.s.
        • Contact:
          • Olga Rosinska, MD
      • Košice, Slovakia
        • Recruiting
        • Eastern Slovak Oncology Institute
        • Contact:
          • Igor Andrasina, MD, PhD
      • Michalovce, Slovakia
        • Recruiting
        • Faculty Hospital with Policlinic of Stefan Kukura
        • Contact:
          • Gabriela Hermanova, MD
      • Nove Zamky, Slovakia
        • Recruiting
        • Faculty Hospital with Policlinic
        • Contact:
          • Pavol Demo, MD
      • Partizanske, Slovakia
        • Recruiting
        • Outpatient Oncology Clinic
        • Contact:
          • Alexandra Szabova, MD
      • Presov, Slovakia
        • Recruiting
        • Faculty Hospital of J.A. Reiman
        • Contact:
          • Jaroslava Leskova, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
IV infusion
IV infusion
IV infusion
Experimental: BCD-100
BCD-100 3 mg/kg Q3W
IV infusion
Anti-PD-1 monoclonal antibody, IV infusion
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 3 years
The time from the date of randomization until death
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 1 year
The time from the date of randomization until progression of disease according to RECIST 1.1 and iRECIST or death
1 year
Overall Response Rate (ORR)
Time Frame: 1 year
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
Disease Control Rate (DCR)
Time Frame: 1 year
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
Time to Response (TTR)
Time Frame: 1 year
TTR will be calculated from the randomization date
1 year
Duration of Response (DOR)
Time Frame: 1 year
DOR will be calculated from the moment of registration of response till event (disease progression or death)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Yulia N Linkova, MD, PhD, Director of Clinical Development Department, BIOCAD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2019

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

April 10, 2019

First Submitted That Met QC Criteria

April 10, 2019

First Posted (Actual)

April 11, 2019

Study Record Updates

Last Update Posted (Actual)

September 17, 2020

Last Update Submitted That Met QC Criteria

September 15, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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