A Study to Evaluate Subcutaneous Durvalumab in Patients With Non-Small Cell Lung Cancer and Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2a, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of Subcutaneous Durvalumab in Patients With Non-Small Cell and Small Cell Lung Cancer - SCope-D1

Conditions
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Non-Small Cell Lung Cancer, Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with NSCLC<br>Patients with Non-Small Cell Lung Cancer | Drug: Durvalumab<br>* Anti-PD-L1 antibody<br>* Other names: MEDI4736, IMFINZI;|
| Experimental: Patients with SCLC<br>Patients with Small Cell Lung Cancer | Drug: Durvalumab<br>* Anti-PD-L1 antibody<br>* Other names: MEDI4736, IMFINZI;Drug: Cisplatin<br>* Chemotherapy<br>Drug: Carboplatin<br>* Chemotherapy<br>Drug: Etoposide<br>* Chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed serum concentration (Ctrough) |  | Approximately 16 months | 
| Number of patients with injection site reactions and immune-mediated reactions |  | Approximately 16 months | 
| Maximum observed serum concentration (Cmax) |  | Approximately 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum observed serum concentration (tmax) of durvalumab |  | Approximately 16 months | 
| Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab |  | Approximately 16 months | 
| Incidence of Adverse Events |  | Approximately 16 months | 
| 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 | 
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in clinical chemistry | 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) | Approximately 16 months | 
| Safety and tolerability of SC dosing of durvalumab in participants with unresectable stage III NSCLC as assessed by abnormality in haematology | Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count. | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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imfinzi, durvalumab