A Phase III, Study to Investigate the Efficacy, Safety, and Pharmacokinetics of ZRC-3276 Versus Opdivo® (Nivolumab) in Subjects with locally advanced or Metastatic Non-Small Cell Lung Cancer
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2022/12/047923
- Lead Sponsor
- Zydus Lifesciences Ltd Formerly Cadila Healthcare Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 248
1.Male or female with= 18 years of age
2.Subjects with histologically or cytologically-documented locally advanced or metastatic NSCLC who present with Stage IIIB/IIIC/Stage IV or recurrent or progressive disease following multi-modality therapy (radiation therapy, surgical resection or definitive chemo radiation therapy for locally advanced disease).
Note: Subjects eligible for study therapy after acceptable prior therapy are as specified
below:
o Subjects must have experienced disease recurrence or progression during or after one first line therapy for advanced or metastatic disease.
o A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy. Subjects must have received at least 2 cycles of platinum doublet based chemotherapy before discontinuation for toxicity.
o Maintenance therapy following first line chemotherapy is not considered as a separate regimen of therapy and could comprise continuation of one or more of the agents used in the first-line therapy regimen or switch to another non cross-resistant agent. The initiation of maintenance therapy requires the lack of progressive disease with front-line therapy. Subjects who showed disease progression during or after maintenance therapy will be eligible.
o Treatment given for locally advanced disease is not considered as a line of therapy for advanced disease. Participants with recurrent disease >6 months after platinum containing adjuvant, neoadjuvant or definitive chemo-radiation 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.
o Experimental therapies when given as separate regimen are considered as separate line of therapy. Subject who received experimental therapies for disease progression after fist line therapy will not be eligible.
- Participants who received adjuvant, neoadjuvant chemotherapy or definitive chemo-radiation therapy given for locally advanced disease, and developed recurrent disease within 6 months of completing therapy are eligible.
o Adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) followed by recurrent or metastatic disease within 6 months of completing therapy is considered as first line therapy for advanced disease.
3.With at least one measurable target lesion (based on response evaluation criteria in solid tumors [RECIST] criteria, version 1.1) performed within 28 days of randomization
a. Target Lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
4.Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
5. Subjects who meets following laboratory values (assessed within 28 days prior to randomization):
a. WBCs =2000/µL
b. Neutrophils =1500/µL
c. Platelets =100 X 10³/µL
d. Hemoglobin =9.0 g/dL
e. Serum creatinine of =1.5 X ULN or creatinine clearance >40 mL/minute (using Cockcroft/Gault formula)
f. AST & ALT =1.5 X ULN
g. Total bilirubin = 1.5 X ULN
6. Female subjects who are not pregnant or breastfeeding and at least one of the following conditions applies:
-Are postmenopausal for at least 24 months before the screening visit, OR <br
1. Subjects with CNS metastases, except for treated asymptomatic CNS metastases, provided all of the following criteria are met:
a. Only supra-tentorial metastases allowed (i.e., no metastases to midbrain,
pons, medulla, or spinal cord)
b. No evidence of interim progression or hemorrhage after completion of
CNS-directed therapy
c. No ongoing requirement for corticosteroids as therapy for CNS disease
(anticonvulsants at a stable dose are allowed at least two weeks prior to
screening)
d. No stereotactic radiation within 14 days or whole-brain radiation within 28
days prior to randomization
e. Leptomeningeal disease (i.e. carcinomatous meningitis)
2.History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti- HCV at Screening.
3. History of human immunodeficiency virus (HIV) antibody positive, or tests
positive for HIV at Screening.
4. Other active malignancy requiring concurrent intervention.
5. Subject with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to screening AND no additional therapy is required or anticipated to be required during the study period.
6. Subject with a condition requiring systemic treatment with either corticosteroids ( >10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
7. Subject with active, known or suspected autoimmune disease. Subject with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
8. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue not resolved to grade 1 (NCI CTCAE version 5) or baseline before
administration of study drug.
9. Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor
agents.
10. Prior radiotherapy or radiosurgery received within 2 weeks prior to screening.
11. Prior treatment with Nivolumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD-137, or anti-CTLA-4 antibody (including ipilimumab or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways)
12. Subject with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
13. Subject not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
14. History of severe hypersensitivity reactions to other monoclonal antibodies.
Allergy or intolerance (unacceptable adverse event) to study drug components, or
Polysorba
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method