A Study to Evaluate Subcutaneous Durvalumab in Patients With Non-Small Cell Lung Cancer and Small Cell Lung Cancer (SCope-D1)

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

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.

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer; Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Durvalumab; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40705
    • Research Site
  • Taipei City, Taiwan, 114
    • Research Site
  • Taipei City, Taiwan, 11217
    • Research Site
• United States
  • Texas
    • Houston, Texas, United States, 77090
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Suli Bolus, MD, AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): August 30, 2023
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: durvalumab; imfinzi
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Durvalumab
• Other Study ID Numbers: D9072C00001; 2020-006041-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No