Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Locally Advanced NSCLC, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Antineoplastic Agents, Immunological, Antineoplastic Agents, Durvalumab
Brief summary
The purpose of this Phase II, open-label, multicentre, single-arm study is to assess efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) in participants with locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC), who have not progressed following platinum-based concurrent or sequential chemoradiotherapy (cCRT or sCRT).
Detailed description
This is a Phase II, open-label, multicentre, single-arm study assessing the efficacy and safety of durvalumab in combination with oleclumab in participants with locally advanced (Stage III), unresectable NSCLC with WHO performance status of 0 or 1, who have not progressed on prior platinum-based CRT. All participants will be assigned to receive durvalumab and oleclumab as an IV infusions for up to 12 months (last dose should be administered at week 48). The last administration at Week 48, or until clinical progression, confirmed RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or an intervention discontinuation criterion is met. The results of this study will provide clinical data on efficacy and safety of an innovation treatment in the new region - Russian Federation.
Interventions
DRUGOleclumab
Oleclumab IV (intravenous infusion)
DRUGDurvalumab
Durvalumab IV (intravenous infusion)
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants will receive durvalumab and oleclumab as an IV infusions
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must be ≥ 18 years at the time of screening. * Histologically-documented NSCLC and have been treated with concurrent or sequential CRT for locally advanced, unresectable (Stage III) disease. * Documented tumour PD-L1 status by qualified lab (local or central). * Documented EGFR and ALK wild-type status (local or central). * Patients must not have progressed following definitive, platinum based, concurrent or sequential chemoradiotherapy. * Participants must have received at least 2 cycles of platinum-based chemotherapy before or concurrent with radiation therapy. * 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 enrolled. Radiation therapy should be administered by intensity modulated RT/volumetric modulated arc therapy (preferred) or 3D-conforming technique. * WHO performance status of 0 or 1. * Adequate organ and marrow function.
Exclusion criteria
* 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, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease. * Mixed small cell and non-small cell lung cancer histology. * Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based CRT. * Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia). * Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy. * History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to study treatment assignment. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis. * Active or prior documented autoimmune or inflammatory disorders (with exceptions). * 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) at 12 months | From date of first dose until 12 months | PFS12 is defined as the Kaplan-Meier estimate of PFS at 12 months per RECIST 1.1 as assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) at 6, 18, and 24 months | From date of first dose until 24 months | PFS6, PFS18 and PFS24 are defined as the Kaplan-Meier estimate of PFS at 6 months, 18 months and 24 months respectively, per RECIST 1.1 as assessed by the investigator. |
| Progression Free Surival (PFS) | Up to 24 months after the last patient's first dose | PFS is defined as time from the start of treatment until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause. |
| Overall survival (OS) at 12 and 24 months | From date of first dose until 12 and months, respectively | OS12 and OS24 are defined as the Kaplan-Meier estimate of OS at 12 months and 24 months respectively |
| Overall Survival (OS) | Up to 24 months after the last patient's first dose | OS is defined as time from the start of treatment until the date of death due to any cause |
| Objective response rate (ORR) | Up to 24 months after the last patient's first dose | ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), as determined by the investigator per RECIST 1.1 |
| Duration of response (DoR) | Up to 24 months after the last patient's first dose | DoR is defined as the time from first response until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause |
| Time to Response (TTR) | Up to 24 months after the last patient's first dose | TTR is defined as the time from the start of the treatment to the first documented objective tumor response observed for participants who achieved CR or PR, as determined by the investigator according to RECIST 1.1 |
Countries
Russia
Outcome results
None listed