Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Durvalumab: Patients will be randomized in a 2:1 ratio to either Durvalumab or Placebo Patients with complete response Partial response or stable disease at 8 weeks tumor evaluation wil
Sponsors
AstraZeneca AB
Eligibility
Inclusion criteria
Inclusion criteria: 1. Capability to give signed informed consent that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol 2. Provision of signed and dated written ICF prior to any mandatory study-specific procedures sampling and analyses Histologically or cytologically documented NSCLC and present with locally advanced unresectable (Stage III) disease (according to Version 8 of the (IASLC Staging Manual in Thoracic Oncology]). Positron emission tomography/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis. 4. Receipt of concurrent or sequential chemoradiation therapy, which must be completed within 1 to 28 days prior to first dose of IP in the study. -For cCRT, patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy. The last dose of chemotherapy must be prior to, or concurrent with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted, but no more than 2 cycles of induction chemotherapy prior to cCRT is acceptable. -For sCRT, patients must have received at least 2 cycles of platinum-based chemotherapy before radiation therapy. The interval between administration of the last dose of chemotherapy regimen and start of RT must be no more than 6 weeks. Consolidation chemotherapy after radiation is not permitted. (i) Note: If a patient receives only 1 cycle of platinum-based chemotherapy concurrent with radiation treatment, this patient will be eligible for the study to participate in the sCRT stratum. -The platinum-based chemotherapy regimen must contain cisplatin or carboplatin and 1 of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local SoC regimens. (Gemcitabine is not included.) -Patients must have received a total dose of radiation of 60 Gy ±10% (54 to 66 Gy) to be randomised as part of the chemoradiation therapy. Study sites are encouraged to adhere to the following mean organ radiation dosing: (i) Mean lung dose must be (ii) Mean oesophagus dose must be (iii) Heart V45 must be ? Study sites should be aware of the recent RTOG 0617 Trial data demonstrating that doses higher than 60 Gy may be associated with greater toxicity and worse efficacy. 5. No progression following definitive, platinum-based, concurrent or sequential chemoradiation therapy 6. Tumor PD-L1 status, with the Ventana SP263 PD-L1 IHC assay determined by a reference laboratory, must be known prior to randomization. Patient with unknown PD-L1 status is not eligible for the study. “Unknown ? refers to (1) insufficient sample which is not able to be analyzed, or (2) sample could be analyzed but results not interpretable. 7. Documented EGFR and ALK status (locally or centrally) at Screening. If the local laboratory will perform the test, a well-validated, local regulatory-approved kit must be used. - EGFR and ALK status must be available prior to randomisation. After approximately 15% EGFR or ALK mutant patients have been
Exclusion criteria
Exclusion criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. History of allogeneic organ transplantation 2. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician - Patients with celiac disease controlled by diet alone 3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent History of another primary malignancy except for - Malignancy treated with curative intent and with no known active disease =5 years before the first dose of investigation product (IP) and of low potential risk for recurrence - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated carcinoma in situ without evidence of disease 5. History of active primary immunodeficiency 6. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and tuberculosis testing inline with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C (HCV), or human immunodeficiency virus(positive human immunodeficiency virus [HIV] 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 7. Mixed small cell and NSCLC histology 8. Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 from the prior chemoradiation therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study treatment may be included (eg, hearing loss) after consultation with the AstraZeneca Study Physician. 9. Patients with Grade =2 pneumonitis from prior chemoradiation therapy 10. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients Prior/concomitant therapy 11. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment other than those under investigation in this st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of Durvalumab treatment compared with placebo in terms of Progression Free SurvivalTimepoint: Progression Free Survival Time frame approximately 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| • To further assess the efficacy of durvalumab compared with placebo in terms of OS24, ORR, DoR, PFS12, PFS18, PFS2, and TTDM Timepoint: Time Frame Approximately 5 years;To assess symptoms and health related quality of life in patients treated with Durvalumab compared with placebo using EORTC QLQ C30 v3 and QLQ LC13Timepoint: Overall Survival Time Frame approximately 5 years;To assess the PK of DurvalumabTimepoint: Time Frame approximately 5 years;To further access the efficacy of Durvalumab compared with Placebo in terms of OSTimepoint: OS analysis will occur when approximately 255 death events have occurred;To investigate the immunogenicity of DurvalumabTimepoint: Time Frame Approximately 5 years;To investigate the relationship between a patients baseline tumor PD L1 expresssion and efficacy outcome with durvalumab compared with placeboTimepoint: Time Frame approximately 5 years;To investigate the relationship between a patients tissue TMB and efficacy outcomes with DurvalumabTimepoint: Time frame approximately 5 years | — |
Countries
China, India, Mexico, Philippines, Poland, Republic of Korea, Russian Federation, Taiwan, Turkey
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed