A study to compare the efficacy and safety of INTP24 against Avastin® in patients with lung cancer.

Phase 3

• Conditions: Malignant neoplasm of unspecifiedpart of bronchus or lung,

• Registration Number: CTRI/2019/08/020665
• Lead Sponsor: Intas Pharmaceuticals Ltd Biopharma Division

Brief Summary

Lung cancer remains a major cause of morbidity and mortality worldwide, accounting for more deaths than any other cancer cause. Lung cancer has been the most common cancer in the world for several decades. Risk factors for lung cancer are smoking, genetic mutation/predisposition, and occupational/environmental exposure. Biosimilarity of a monoclonal antibody can be established by demonstrating comparable clinical efficacy of the biosimilar and the reference medicinal product in adequately powered, randomised, parallel group comparative clinical trial(s), by using efficacy end points in a study population that is representative of approved therapeutic indication(s) of the reference product and is sensitive for detecting potential differences between the biosimilar and the reference product. To establish the biosimilarity between the test and reference bevacizumab, Intas Pharmaceuticals Limited, India will be conducting this comparative clinical study with the aim of comparing the efficacy and safety of INTP24 (biosimilar bevacizumab) with that of Avastin (Roche Registration Limited, United Kingdom) in patients with advanced, unresectable or metastatic non-squamous non-small cell lung cancer. The study will be a randomized, double-blind, multicentre, multinational, parallelgroup, active-controlled, comparative clinical trial. The study will enrol female or male patients aged greater than or equal to 18 years and having histologically or cytologically-confirmed locally advanced, unresectable or recurrent or metastatic non-squamous non-small cell lung cancer with Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. Each enrolled patients will be randomized to receive either bevacizumab manufactured by Intas Pharmaceuticals Limited, India or Avastin of Roche Registration Limited, United Kingdom as per randomization schedule generated. All patients will receive intravenous injection of 15 mg/kg of bevacizumab in 21-day cycles. 594 patients will be enrolled.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-15
• Last Update Posted: 2021-09-06

Recruitment & Eligibility

• Status: Other
• Sex: All
• Target Recruitment: 594

Inclusion Criteria

• Patient of either gender and aged greater than or equal to 18 years 2.
• Patient having histologically or cytological confirmed predominately nonsquamous, non-small cell lung cancer.
• Patients with locally advanced, unresectable or metastatic non-small cell lung cancer or recurrent non-small cell lung cancer according to The Union for International Cancer Control (UICC) staging system.
• At-least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 or higher criteria.
• For patients with recurrent disease, at least 6 months must have elapsed since completing adjuvant or neoadjuvant treatment 6.
• ECOG performance status less than or equal to 2.
• Patient should be eligible to receive study treatment of bevacizumab, paclitaxel, and carboplatin for the treatment of locally advanced or recurrent or metastatic non-squamous NSCLC.
• Patient must have an adequate bone marrow, renal and hepatic function 9.
• Women of childbearing potential and partners of sexually active males must agree to use an accepted and effective method of contraception (oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, / and if males, absolute sexual abstinence, use of condom with spermicide by sexual partner or temporarily sterile [at least 6 months prior to study drug administration] sexual partner) for the duration of the study and for at least 6 months after the last dose of the study treatment or permanently sterile.
• Female patients who are not of childbearing potential should have undergone a documented hysterectomy and/or bilateral oophorectomy or have achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (status may be confirmed at Investigator discretion by having a serum follicle stimulating hormone (FSH) level) 10.
• Patients able to understand the investigational nature of this study and give written informed consent prior to the participation in the trial and able to comply with study requirement in the opinion of Principal Investigator.

Exclusion Criteria

• Patient who has documented evidence of sensitizing epidermal growth factor receptor (EGFR) mutations or EML4-ALK translocation positive mutations.
• Prior systemic therapy for non-small cell lung cancer (adjuvant or neoadjuvant therapy in case of recurrent disease will be allowed).
• Prior immunotherapy or bevacizumab therapy.
• Concurrent treatment with other anticancer therapies (excluding that defined in the protocol).
• Bone directed therapies like bisphosphonates and denosumab will be allowed.
• Pregnant and breast-feeding women.
• Male patients with current pregnant partners will not be eligible.
• History of local radiation therapy for bone metastases within last 1 month prior to the day of randomization.
• Patients with a history of gross haemoptysis (defined as bright red blood of 1/2 teaspoon (2.5 ml) or more) or haemorrhage within last 3 months 8.
• Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic Anticoagulation) 9.
• Current or recent (within 10 days of randomization) use of aspirin (greater than 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol 10.
• Current use of oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for greater than 2 weeks prior to randomization and INR/aPTT is within therapeutic limits (as per the local medical standards) 11.
• Therapeutic anticoagulation and/or coagulation abnormalities (e.g., INR greater than 1.5 and aPTT greater than ULN unless on prophylactic anticoagulation).
• Patient with known brain metastases.
• Patients with non-healing wound ulcer, or bone fracture, or major surgical procedure, open biopsy, or significant traumatic injury within last 28 days or anticipation of need for major surgical procedure during the study.
• Patients with history of gastrointestinal perforation, tracheoesophageal fistula or any grade 4 fistula 15.
• Patients with clinically significant cardiac diseases like New York Heart Association (NYHA) Grade II or greater, congestive heart failure (multigated acquisition [MUGA] or echocardiogram [ECHO]), unstable angina pectoris, myocardial infarction, cardiac arrhythmia, cerebral infarction, or transient ischemic attacks.
• Uncontrolled hypertension (systolic blood pressure [BP] greater than 140 or diastolic BP greater than 90 mmHg) (Patients with hypertension controlled by antihypertensive therapies are eligible).
• Patients with a prior history of hypertensive crisis and hypertensive encephalopathy 18.
• Patient with ongoing or active infection (patient should be off anti-infective to be eligible for participation).
• A known case of or positive test for human immunodeficiency virus (HIV) infection or hepatitis B or hepatitis C virus (HCV).
• Peripheral motor or sensory neuropathy of grade greater than 2.
• Known hypersensitivity to any components of the study medications / chemotherapy / supportive medications or its ingredients that can impact treatment.
• Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and patient having a disease-free survival greater than or equal to 5 years.
• The receipt of an IMP, or participation in a drug research study within a period of 30 days (or as per the respective national regulations) prior to the first dose of the IMP (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study).
• Any other medical conditions (including mental illness, substance abuse, social situations) deemed by the clinician to be likely to interfere with a subject ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparision of efficacy and establishment of therapeutic equivalence of INTP24 (bevacizumab) with Avastin.	Every 6 weeks until 18 weeks and thereafter every 9 weeks until 1 year

Secondary Outcome Measures

Name	Time	Method
Comparision of safety and immunogenicity of INTP24 and Avastin.	Comparision of the pharmacokinetics of INTP24 and Avastin.

Trial Locations

Locations (56)

Action Cancer Hospital; 🇮🇳 Delhi, DELHI, India

All India Institute of Medical Sciences; 🇮🇳 Khordha, ORISSA, India

Asian Institute of Medical Sciences; 🇮🇳 Faridabad, HARYANA, India

Care Hospital; 🇮🇳 Hyderabad, TELANGANA, India

Deeenanath Mangeshkar Hospital and Research Centre; 🇮🇳 Pune, MAHARASHTRA, India

Delhi State Cancer Institute; 🇮🇳 East, DELHI, India

Dr. Ram Manohar Lohia Institute of Medical Sciences; 🇮🇳 Lucknow, UTTAR PRADESH, India

Erode Cancer Centre; 🇮🇳 Erode, TAMIL NADU, India

Government Medical College & Hosiptal,; 🇮🇳 Nagpur, MAHARASHTRA, India

HCG Cancer Centre; 🇮🇳 Ahmadabad, GUJARAT, India

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Action Cancer Hospital

🇮🇳Delhi, DELHI, India

Dr Ajay Sharma

Principal investigator

09999379838

ajaysharma04@rediffmail.com