A Phase III Randomised, Double-blind, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity between SB27 (proposed pembrolizumab biosimilar) and Keytruda in Subjects with Metastatic Non-squamous Non-small Cell Lung Cancer

JRCT ID: jRCT2061230106

Registered date:11/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Metastatic non-squamous non-small cell lung cancer
• Date of first enrollment: 11/03/2024
• Target sample size: 46
• Countries of recruitment: Bosnia & Herzegovina,Japan,Brazil,Japan,Georgia,Japan,Germany,Japan,India,Japan,Malaysia,Japan,Mexico,Japan,Philippines,Japan,Romania,Japan,Serbia,Japan,Spain,Japan,Thailand,Japan,Turkey,Japan
• Study type: Interventional
• Intervention(s): SB27 200 mg IV every 3 weeks.

Outcome(s)

Primary Outcome

ORR at Week 24
Defined as the proportion of subjects achieving a complete response (CR) or partial response (PR) at Week 24 according to RECIST v1.1 based on BICR. Confirmation of response will not be considered for the analysis of primary efficacy endpoint.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Subjects who have a histologically confirmed or cytologically confirmed diagnosis of stage IV (M1a, M1b, or M1c of American Joint Committee on Cancer [AJCC] 8th edition) non-squamous NSCLC.
2. Subjects who have at least one measurable lesion per RECIST v1.1 criteria on imaging modalities (computed tomography [CT] scan or magnetic resonance imaging [MRI] scan) by the local site Investigator assessment.
3. Subjects who have a documented PD-L1 result by the US FDA-approved test (PD-L1 IHC 22C3 pharmDx assay) within 12 weeks from the date of Randomisation.
a. If no prior PD-L1 result is available at Screening, the subject must be assessed for PD-L1 result prior to the date of Randomisation using the stated method (PD-L1 IHC 22C3 pharmDx assay) at a qualified local laboratory. For PD-L1 assessment, newly obtained (core or excisional) biopsy or archival tumour tissue sample (obtained within 12 weeks from the date of Randomisation) from locations not irradiated prior to biopsy is acceptable and formalin-fixed paraffin embedded (FFPE) tumour tissue sample blocks are preferred. Fine needle aspirates/biopsy, brushing, cell blocks, or tumour tissue from bone metastases that is subject to decalcification are not acceptable.
4. Subjects who have NOT received prior systemic therapy (including cytotoxic chemotherapy, targeted therapy, or antineoplastic biological therapy) for their metastatic NSCLC.
5. Male or female aged >= 18 years old at the time of signing the informed consent form (ICF), if local regulations are different in this regard, follow the local regulations.
6. ECOG performance status of 0 or 1.
7. Subjects who have a life expectancy of at least 3 months from Screening.
8. Subjects must be able to provide informed consent, which must be obtained prior to any study related procedures.
9. Female subjects of non-childbearing potential female (e.g., having congenital or acquired condition that prevents childbearing, having history of hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, or postmenopausal [defined as amenorrhea of at least 12 months without an alternative medical cause prior to Screening and a follicle stimulating hormone (FSH) level of > 40 international unit (IU)/L at Screening]), OR childbearing potential who have a negative urine or serum pregnancy test within 3 days prior to receiving the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
10. Must agree to use adequate methods of contraception starting with the first dose of study treatment through 4 months after the last dose of IP administration and 6 months after the last dose of non-IPs administration.
11. Subjects must have adequate organ functions at Screening as indicated by the clinical laboratory values.

Exclude criteria

1. Subjects who have documentation of presence of tumour activating EGFR mutations OR presence of ALK rearrangements OR presence of ROS1 rearrangements.
2. Subjects who are currently receiving or have received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
a. Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent OR an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, LAG-3, TIGIT, OX40, and CD137, etc.).
3. Subjects who have received prior palliative radiotherapy within 2 weeks prior to the date of Randomisation or received lung radiation therapy of > 30 Gray (Gy) within 6 months prior to the date of Randomisation. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
4. Subjects who have predominantly squamous cell histology NSCLC. Mixed tumours will be categorised by the predominant cell type; if small cell elements are present, the subject is ineligible.
5. Subjects who have a known severe hypersensitivity reaction to treatment with another monoclonal antibody, any ingredient contained in SB27 or Keytruda, or any component of platinum-containing compounds or pemetrexed.
6. Subjects who are unable or unwilling to take folic acid or vitamin B12 supplementation.
7. Subjects who are currently participating in any interventional clinical study or have participated in a study of an investigational drug within 30 days or 5 half-lives of the investigational drug being studied prior to the date of Randomisation, whichever is longer, or using an investigational device within 30 days prior to the date of Randomisation.
8. Subjects who are expected to require any other form of systemic or localised antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC, radiation therapy, or surgical resection).
9. Subjects who have a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis.
10. Subjects who have a history of interstitial lung disease (e.g., idiopathic pulmonary fibrosis or organising pneumonia).
11. Subjects who have a history of malignancy other than NSCLC except if the subjects have undergone potentially curative therapy with no evidence of that disease recurrence for 5 years prior to Screening.
12. Subjects who have known untreated central nervous system (CNS) metastases or known carcinomatous meningitis.
a. Subjects with untreated and asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no surrounding oedema, and no lesion >= 1.0 cm) first detected at Screening may participate, but will require regular scan of the brain as a site of disease.
b. Subjects with previously treated brain metastases may participate provided that they are clinically and neurologically stable, and have no evidence of new or enlarging brain metastases (as determined by 2 brain images, both of which are obtained after treatment of the brain metastases. One of the brain images should be a brain image obtained at Screening and the other should be a brain image obtained at least 4 weeks prior to Screening). In addition, they are off systemic steroids for at least 2 weeks prior to the date of Randomisation.
13. Subjects with an active or known autoimmune disease that has required systemic treatment including disease modifying agents, corticosteroids, or immunosuppressive drugs within 1 year prior to the date of Randomisation, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
14. Subjects who have an active infection requiring systemic therapy within 2 weeks prior to the date of Randomisation or history of severe infections within 4 weeks prior to the date of Randomisation, including, but not limited to, hospitalisation for complications of infection, bacteraemia, or severe pneumonia.
15. Subjects who have a positive test result for human immunodeficiency virus (HIV) at Screening, or have a history of acquired immunodeficiency syndrome (AIDS) or a history of primary immunodeficiency.
16. Subjects with history of active infection (acute or chronic) or positive test of hepatitis B virus (HBV, defined as hepatitis B surface antigen [HBsAg] positive OR HBsAg negative and hepatitis B core antibody [HBcAb] positive) and hepatitis C virus (HCV, defined as HCV ribonucleic acid [RNA] positive).
17. Subjects who have any clinically significant disease or disorder or laboratory abnormality that prevent the subjects from completing the study or might confound the results of the study at the discretion of the Investigator.
18. Subjects who have a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
19. Subjects who are a regular user of any illicit drugs or had a recent history of substance abuse (including alcohol) within 1 year prior to Screening.
20. Subjects who have clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or peritoneal carcinomatosis.
21. Women who are pregnant or nursing at Screening, men and women planning pregnancy during the study, or women who are planning to breastfeed during the study.
22. Subjects who have received a live, or live attenuated vaccine within 30 days prior to the date of Randomisation.
a. Killed, inactivated, or recombinant vaccine is allowed.
b. Non-live or non-live attenuated Coronavirus Disease 2019 (COVID-19) vaccines (including messenger ribonucleic acid [mRNA]-based vaccines) are permitted.
c. Seasonal influenza vaccines that do not contain a live or live-attenuated virus are permitted.
23. Subjects who have had major surgery within 4 weeks prior to the date of Randomisation and inadequate wound healing at the discretion of the Investigator at Screening (e.g., requiring more extensive procedure than local anaesthesia [involving general anaesthesia or respiratory assistance or regional anaesthesia] or open lung biopsy) or expected major surgical procedure during the study.
24. Subjects who are unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose <= 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam) and subjects who require phenytoin or fosphenytoin.
25. Subjects who have a known history of active TB.
26. Subjects who have had an allogeneic tissue/solid organ transplant.
27. Subjects who are on any systemic corticosteroid therapy or on any other form of immunosuppressive medication within 2 weeks prior to the date of Randomisation. The following are exceptions to this criterion:
a. Intranasal steroids, inhaled steroids, topical steroids, or local steroid injections (e.g., intra-articular injection).
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
c. Steroids as premedication for hypersensitivity reactions (e.g., premedication for CT scan).
28. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).

Related Information

• Primary Sponsor: Umezawa Daisuke