This is a clinical study to compare Dr Reddy’s developed nivolumab vs. nivolumab originator in patients with Advanced lung cancer who have failed with previous chemotherapy.
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2024/04/066248
- Lead Sponsor
- Dr. Reddys Laboratories Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Patients of either gender greater than or equal to 18 to less than or equal to 75 years of age.
2. Patients capable and willing to voluntarily provide informed consent for participation as per the locally applicable regulations.
3. Patients must be willing and able to comply with the study requirements.
4. Patients with ECOG performance status score of 0 or 1.
5. Patients with histologically- or cytologically-documented squamous cell NSCLC who present with Stage IIIB or Stage IIIC or Stage IV disease, or with recurrence or progressive disease following multimodal therapy (radiation therapy, surgical resection or definitive chemoradiation therapy for locally advanced disease). The diagnosis of disease indication should be by a biopsy which was excisional, incisional or core needle. Fine needle aspiration is considered as insufficient for confirmation of the diagnosis.
6. Patients must have experienced disease recurrence or progression while on treatment or after at least one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
a. Patients with known EGFR, and ALK genomic tumour aberrations should have disease progression on trait specific therapy for these aberrations prior to receiving nivolumab.
b. Maintenance therapy following platinum doublet-based chemotherapy is NOT considered as a separate regimen of therapy.
c. Patients who received platinum-doublet containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.
d. Patients with recurrent disease greater than 6 months after platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence, are eligible.
7. Patients should have received only one treatment line of therapy for metastatic disease.
8. Patients must have measurable disease [at least one measurable target lesion] by CT or MRI as per RECIST criteria (Version 1.1) in the radiographic tumor assessment performed within 28 days of randomization.
a. The target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site [the documented evidence should be between the completion of radiotherapy and the randomization day].
9. Laboratory values must meet the following criteria for adequate bone marrow function. If values are outside the margin, investigator justification is needed:
a. Total WBC count greater than or equal to 2000 per mm3,
b. ANC greater than or equal to 1500 per mm3,
c. Platelet count greater than or equal to 1,00,000 per mm3,
d. Haemoglobin greater than or equal to 9.0 g per dL.
10. Laboratories values must meet the following criteria for appropriate renal and liver function status. If values are outside the margin, investigator justification is needed:
a. Serum creatinine of less than or equal to 1.5 X ULN or creatinine clearance greater than 40 mL/minute (using Cockcroft/Gault formula)
Female CrCl - (140 - age in years) X weight in kg X 0.85/72 X serum creatinine in mg per dL
Male CrCl - (140 - age in years) X weight in kg X 1.00/72 X serum creatinine in mg per
1. Patients with CNS metastases are eligible only if the metastases are adequately treated. In this case, patients should have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization and should be either off corticosteroids, or on a stable or decreasing dose of less than or equal to 10 mg prednisone per day (or equivalent).
2. Patients with carcinomatous meningitis.
3. Patients with a known active or suspected autoimmune disease. Patients with type I diabetes mellitus, autoimmune hypothyroidism controlled with thyroid hormone replacement, autoimmune skin disorders (such as vitiligo, psoriasis, or immune mediated alopecia) not requiring systemic treatment and patients whose autoimmune conditions having well identified and avoidable triggers are permitted to enrol.
4. Patients with a condition requiring systemic treatment with either corticosteroids (higher than 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
Note: Topical, ocular, otological, intra-articular, intranasal, and inhalational corticosteroids are permitted. Adrenal substitutive glucocorticoids are allowed even at doses higher than 10 mg daily prednisone (or equivalent) if needed due to stress, in the absence of active autoimmune disease.
5. Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
6. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
7. Any other active malignancy requiring concurrent intervention.
8. History of previous malignancies except non-melanoma skin cancers, or in situ cervical or breast cancer unless a complete remission was achieved at least 2 years prior to randomization AND no additional therapy is required during the study period. Patients having hepatic involvement of cancer should be excluded as per investigator assessment.
9. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI-CTCAE, Version 5.0 or a recent version) or baseline before administration of study drug.
10. Patients must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
11. History of or current abuse of alcohol or illegal drugs (testing not required).
12. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
13. Positive test for hepatitis B virus (HBsAg) or hepatitis C virus other than positive hepatitis B surface antibody test in vaccinated patients.
14. History of allergy or intolerance (unacceptable adverse event) to study drug components [Disodium succinic salt hexahydrate, Succinic acid, Sodium chloride, Trehalose dihydrate, Methionine, Pentetic acid (DTPA), Polysorbate 80].
15. History of severe hypersensitivity reactions to other monoclonal antibodies.
16. Ongoing or planned administration of anti-cancer therapies other than those specified in this study.
17. Treatment with any investigational agent within 28 days of first administration of study drug.
18. Any
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Proportion of patients achieving best overall response rate (BORR) up to Week 25. BORR is defined as proportion of patients who have achieved complete responses and partial responses (CR + PR) across all the visits as per RECIST 1.1 criteria based on blinded independent imaging tumor assessment.Timepoint: Base-line to Week 25
- Secondary Outcome Measures
Name Time Method Efficacy Endpoints: <br/ ><br>ORR at Week 9, 17 and 25 <br/ ><br>OS till Week 25 <br/ ><br>PFS till Week 25 <br/ ><br>Safety Endpoint: <br/ ><br>Comparison of the incidence of AEs, AESI and SAEs between patients randomized to DRL_NU and RMP. <br/ ><br>Immunogenicity Endpoint: <br/ ><br>Comparison of the incidence of ADAs, NAb and titre between patients randomized to DRL_NU and RMP. <br/ ><br>Pharmacokinetic Endpoint: <br/ ><br>Descriptive comparison of AUC0-14 days between patients treated with DRL_NU and RMP. <br/ ><br>Descriptive comparison of Ctrough concentrations of nivolumab over time between patients treated with DRL_NU and RMP. <br/ ><br>Other PK parameters that will be compared include: Cmax after first dose, Tmax after first dose and t1/2.Timepoint: Base-line to Week 25