The target population of interest in this study is participants with locally advanced (Stage III), unresectable NSCLC, whose tumours express PD L1 TC = 1% as assessed by a central reference laboratory using the VENTANA PD-L1 (SP263) IHC assay, and who did not progress after definitive platinum based cCRT. MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Conce
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be = 18 years at the time of screening. 2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease 3. Provision of a tumour tissue sample obtained prior to CRT 4. Documented tumour PD-L1 status = 1% by central lab 5. Documented EGFR and ALK wild-type status (local or central). 6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy 7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy 8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique. 9. WHO performance status of 0 or 1 at randomization 10. Adequate organ and marrow function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 942 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 628
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin, cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease. 2. Mixed small cell and non-small cell lung cancer histology. 3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC. 4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT. 5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia). 6. Participants with =grade 2 pneumonitis from prior chemoradiation therapy. 7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis, (= Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis. 8. Active or prior documented autoimmune or inflammatory disorders (with exceptions) 9. Active EBV infection, or known or suspected chronic active EBV infection at screening 10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum-based cCRT, with PD-L1 TC = 50%, progression free survival (PFS) assessed by blind independent committee review (BICR).;Secondary Objective: To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC = 1%, progression free survival (PFS) assessed by Blinded Independent Central Review (BICR). To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC = 1% or TC = 50% in the following outcomes: •Overall response rate (ORR) •Duration of response (DoR) •Time to second progression (PFS2) •Time to death or distant metastatis (TTDM) •Time to First Subsequent Therapy (TFST) •PFS at 6, 12, 18 and 24 months •Overall Survival at 24 months (OS 24) • Overall Survival (OS) •PFS as assessed by investigator •Time to deterioration in pulmonary symptoms Test the above objectives using an alternative PD-L1 IHC assay, PD-L1 IHC 22C3 pharmDx PK and immunogenicity of durvalumab and domvanalimab To assess the safety and tolerability of durvalumab plus domvanalimab as compared to durvalumab plus placebo.;Primary end point(s): Progression Free Survival (PFS) using Blinded Independent Central Review (BICR) assessment according to RECIST 1.1 with participants with PD-L1 TC>=50%.;Timepoint(s) of evaluation of this end point: PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS measured by hazard ratio (HR), in participants with PD-L1 TC = 1%. % as assessed by BICR. Comparison of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC = 1% or TC = 50% in the following outcomes 1. Overall Survival (OS) 2. PFS assessment by investigator according to RECIST 1.1 3. PFS6, PFS12, PFS18, PFS24 4. Overall Survival at 24 months (OS 24) 5. Objective response rate (ORR) using BICR assessment according to RECIST 1.1. 6. Duration of response (DoR) using BICR assessment according to RECIST 1.1 7. Time from randomization to second progression (PFS2) 8. Time from randomization until the first date of distant metastasis or death in the absence o distant metastasis (TTDM). 9. Time to first subsequent therapy (TFST) 10. The pharmacokinetics (PK) of durvalumab and domvanalimab as determined by concentration. 11. The immunogenicity of Durvalumab and domvanalimab as assessed by presence of anti-drug antibodies (ADAs) 12. Time to First Confirmed Deterioration (TTFCD)in pulmonary symptoms measured by the NSCLC-SAQ. 13. Test the above objectives using an alternative PD-L1 IHC assay, PD- L1 IHC 22C3 pharmDx;Timepoint(s) of evaluation of this end point: PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans. ORR, DoR, PFS by investigator, PFS2, PFS6, PFS12, PFS18, PFS24, TTDM, TFST, TTFCD, up to approximately 8 years after first patient randomized OS and OS24, up to approximately 8 years after first patient randomized. ADA and PK: from date of randomization to approximately 12 weeks after last IP dose. | — |
Countries
Belgium, Brazil, Chile, China, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Norway, Philippines, Poland, Romania, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Study Information Center
AstraZeneca AB
Outcome results
None listed