Non-Small Cell Lung Cancer, Small Cell Lung Cancer
Conditions
Keywords
imfinzi, durvalumab
Brief summary
This study has 2 parts: dose finding and dose confirmatory. In Part 1, the dose finding phase of the study, there will be 3 or more dosing levels to find out what dose of durvalumab administered as an infusion under the skin acts similarly to durvalumab administered into a vein. 24 participants with Non-Small Cell Lung Cancer will be enrolled for a 12 month treatment period and 3 months follow up In Part 2, the dose confirmation phase of the study, participants will receive the dose of durvalumab identified in Part 1 of the study. The goal of Part 2 will be to learn more about the way that the body processes durvalumab when administered as an infusion under the skin. Approximately 90 participants with Non-Small Cell Lung Cancer will be enrolled; additionally, up to 10 participants with Small Cell Lung Cancer (who will receive concurrent chemotherapy) will be enrolled for a 12 treatment period and a 3 month follow-up period. AstraZeneca has decided to stop further enrollment and the study was terminated when all patients in Part 1 (Phase I) completed their last study visit. No safety issues or clinical concerns however, have been identified for this study. Part 2 (Phase II) was not initiated.
Interventions
DRUGDurvalumab
Anti-PD-L1 antibody
DRUGCisplatin
Chemotherapy
DRUGCarboplatin
Chemotherapy
DRUGEtoposide
Chemotherapy
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented unresectable Stage III NSCLC that has not progressed following definitive platinum based CRT or extensive disease (Stage IV) SCLC * ECOG performance status of 0 or 1 * For participants with SCLC: At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 TL at baseline * Absence of EGFR mutation or ALK rearrangement prior to screening
Exclusion criteria
* History of allogeneic organ transplantation * Autoimmune or inflammatory disorders, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome * Uncontrolled intercurrent illness * History of another primary malignancy * History of active primary immunodeficiency * Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) * Brain metastases or spinal cord compression * Persistent toxicities (CTCAE Grade \>2) caused by previous anticancer therapy, excluding alopecia * Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum observed serum concentration (Cmax) | Approximately 16 months |
| Number of patients with injection site reactions and immune-mediated reactions | Approximately 16 months |
| Observed serum concentration (Ctrough) | Approximately 16 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in WHO/ECOG performance status | Approximately 16 months | — |
| Occurrence of abnormal ECG - PR, QRS, QT, and QT interval corrected by Fridericia's formula intervals | Approximately 16 months | — |
| Time to maximum observed serum concentration (tmax) of durvalumab | Approximately 16 months | — |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in clinical chemistry | Approximately 16 months | Clinical chemistry will be assessed by liver function(Alanine aminotransferase, Aspartate aminotransferase, albumin, total bilirubin), kidney function (e.g. Urea, Creatinine) and endocrine function(TSH, T3 free,T4 free) |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in haematology | Approximately 16 months | Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count. |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (pulse rate) in beats per minute | Approximately 16 months | — |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (respiration rate) in breaths per minute | Approximately 16 months | — |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (temperature) in degrees Celsius | Approximately 16 months | — |
| Incidence of of anti-drug antibodies (ADA) and neutralizing antibodies | Approximately 16 months | — |
| Part 2 only: Overall Response Rate (ORR) - proportion of participants with a complete or partial response to treatment as determined using RECIST 1.1 guidelines | Approximately 16 months | — |
| Part 2 only: Best Objective Response (BoR) - participant's best response following first dose of study drug | Approximately 16 months | — |
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by vital signs (blood pressure in mmHg) | Approximately 16 months | — |
| Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab | Approximately 16 months | — |
| Incidence of Adverse Events | Approximately 16 months | — |
Other
| Measure | Time frame |
|---|---|
| Incidence of injection site reactions reported through ISQ Symptoms questionnaire | Approximately 16 months |
| Treatment satisfaction reported using ISQ Satisfaction questionnaire | Approximately 16 months |
Countries
New Zealand, Spain, Taiwan, United States
Outcome results
None listed