Non-Small Cell Lung Cancer
Conditions
Keywords
non-small cell lung cancer, locally advanced, NSCLC
Brief summary
This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.
Interventions
DRUGDurvalumab
Durvalumab IV (Intravenous infusion)
DRUGDomvanalimab
Domvanalimab IV (Intravenous infusion)
OTHERPlacebo
Placebo IV (Intravenous infusion)
Sponsors
AstraZeneca
Arcus Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Exclusion criteria
1. History of another primary malignancy, except for: * Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence. * Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease . * Adequately treated carcinoma in situ, including Ta tumors 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 | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 5 years after randomization | Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 50%. Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Durvalumab and Domvanalimab | Approximately 12 weeks after last IP dose | The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| PFS6, PFS12, PFS18, PFS24 | Approximately 6, 12, 18 and 24 months after randomization | PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Anti-Drug Antibodies (ADAs) | Approximately 12 weeks after last IP dose. | The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Time to deterioration in pulmonary symptoms (TTFCD) | Approximately 5 years after randomization | Time to deterioration in pulmonary symptoms (TTFCD) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| PFS investigator | Up to 5 years after randomization | Defined as time from randomisation until progression per RECIST 1.1 as assessed by Investigator or death due to any cause in participants Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| OS 24 | Approximately 24 months after randomization | Overall Survival (OS) at 24 months Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Progression Free Survival (PFS) | Up to 5 years after randomization | Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 1% Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Overall Survival (OS) | Approximately 5 years after randomization | Overall Survival (OS) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Objective Response Rate (ORR) | Approximately 5 years after randomization | Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Duration of Response (DoR) | Approximately 5 years after randomization | Duration of Response (DoR) using BICR assessment according to RECIST 1.1 Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Time from randomization to second progression (PFS2) | Approximately 5 years after randomization | Time from randomization to second progression (PFS2) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Time to first subsequent therapy (TFST) | Approximately 5 years after randomization | Time to first subsequent therapy (TFST) Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
| Time from randomization to first date of distant metastasis or death (TTDM) | Approximately 5 years after randomization | Time from randomization until the first date of distant metastasis or death in the absence of distant metastasis (TTDM). Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment. |
Countries
Belgium, Brazil, Canada, Chile, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Malaysia, Mexico, Norway, Philippines, Poland, Romania, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
PRINCIPAL_INVESTIGATORHidehito Horinouchi, MD, PhD
National Cancer Center Hospital
PRINCIPAL_INVESTIGATORAlexander Spira, MD, PhD
Virginia Cancer Specialists Research Institute
PRINCIPAL_INVESTIGATORJinming Yu, MD, PhD
Shandong Cancer Hospital and Institute
Outcome results
None listed