Study of Durvalumab Following Radiation Therapy in Patients With Stage 3 Unresectable NSCLC Ineligible for Chemotherapy

NCT04249362 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: D4194C000092019-004336-31
• Study Type: interventional
• Target: 102
• Locations: 6 countries
• Sites: 35

Brief Summary

This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who are deemed to be ineligible for chemotherapy per Investigator assessment. Patients will be enrolled into 2 cohorts according to radiotherapy pretreatment dose (Cohort A: standard radiation therapy \[60 gray (Gy) ± 10% or hypofractionated bioequivalent dose (BED)\]; Cohort B: palliative radiation therapy \[40 to \< 54 Gy or hypofractionated BED\])

Conditions

Non-small Cell Lung Cancer

Keywords

Radiation therapy; Phase II; Palliative Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Grade 3 and Grade 4 Possibly-related Adverse Events (PRAEs)

  The safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment. A PRAE was any TEAE with a possible relatedness to durvalumab, or where the relatedness was missing. If relatedness of a TEAE was missing at the primary DCO (30 March 2023) the TEAE was considered a PRAE.

  From first dose of durvalumab treatment until 6 months after initiation of durvalumab treatment

Secondary Outcomes (11)

• Median Progression-free Survival (mPFS)

  From the first date of treatment until the date of objective disease progression or death or data cut-off date (36 months)

• Progression-free Survival at 6 Months (PFS6)

  From the first date of treatment until the date of objective disease progression or death (6 months)

• Progression-free Survival at 12 Months (PFS12)

  From the first date of treatment until the date of objective disease progression or death (12 months)

• Median Overall Survival (mOS)

  From the first date of treatment until death or data cut-off due to any cause (36 months)

• Overall Survival at 12 Months (OS12)

  From the first date of treatment until death due to any cause (12 months)

Study Arms (2)

Cohort A

EXPERIMENTAL

Patients received standard radiotherapy \[60 gray (Gy) ± 10% or hypofractionated BED\] prior to study entry.

Drug: Durvalumab

Cohort B

EXPERIMENTAL

Patients received palliative radiotherapy \[40 to \< 54 Gy or hypofractionated BED\] prior to study entry.

Drug: Durvalumab

Interventions

Durvalumab DRUG

All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.

Also known as: MEDI4736

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent.
• Age ≥ 18 years at study entry.
• Histologically or cytologically documented NSCLC with locally-advanced, unresectable Stage III disease.
• Deemed ineligible for chemotherapy per Investigator assessment.
• Receipt of radiation therapy that was completed within 42 days prior to first study drug administration.
• Must have received a total dose of radiation of 40 to 66 Gy (standard or hypofractionated BED).
• Must not have progressed following radiation therapy, as per Investigator assessed RECIST 1.1 criteria: a) Patients with measurable disease and/or nonmeasurable and/or no evidence of disease assessed at baseline by computed tomography /magnetic resonance imaging will be eligible for this study. b) Prior irradiated lesions may be considered measurable and selected as target lesions (TLs) providing they fulfill the other criteria for measurability.
• World Health Organization/ECOG performance status of ≤2.
• No prior exposure to immune-mediated therapy including, but not limited to, anti-CTLA-4, anti-PD-1, anti-PD-L1, and antiprogrammed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
• Patients must have adequate organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1.0 × 109 /L
• Platelet count ≥ 75 × 109/L
• Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome.
• Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × ULN

You may not qualify if:

• Patients with locally-advanced NSCLC whose disease has progressed following radiation therapy.
• Mixed small cell lung cancer and NSCLC histology.
• History of allogeneic organ transplantation.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
• Uncontrolled intercurrent illness (e.g., ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris)
• History of another primary malignancy except for (a) malignancy treated with curative intent and with no known active disease ≥ 5 years before the first study drug administration, (b) adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease, and c) treated carcinoma in situ without evidence of disease.
• History of leptomeningeal carcinomatosis
• History of active primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
• Participation in another clinical study with an IP administered in the last 4 weeks.
• Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Tucson, Arizona, 85704, United States

Location

Research Site

Tampa, Florida, 33612, United States

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Royal Oak, Michigan, 48073, United States

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Research Site

Limoges, 87000, France

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Marseille, 13009, France

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Montpellier, 34070, France

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Nîmes, 30029, France

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Rouen, 76031, France

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Brescia, 25100, Italy

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Florence, 50134, Italy

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Genova, 16132, Italy

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Meldola, 47014, Italy

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Messina, 98158, Italy

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Modena, 41124, Italy

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Monza, 20900, Italy

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Negrar, 37024, Italy

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Pavia, 27100, Italy

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Pisa, 56124, Italy

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Ravenna, 48121, Italy

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Roma, 00128, Italy

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Bialystok, 15-044, Poland

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Gdansk, 80-214, Poland

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Olsztyn, 10-228, Poland

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Szczecin, 71-730, Poland

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Warsaw, 02-781, Poland

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Saint Petersburg, 197002, Russia

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Saint Petersburg, 197758, Russia

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Ufa, 450054, Russia

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A Coruña, 15006, Spain

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Barcelona, 8035, Spain

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Castellon, 12002, Spain

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Madrid, 28050, Spain

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Oviedo, 33011, Spain

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Pamplona, 31008, Spain

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Research Site

Sabadell(Barcelona), 08208, Spain

Location

Related Publications (1)

• Filippi AR, Dziadziuszko R, Garcia Campelo MR, Paoli JB, Sawyer W, Diaz Perez IE. DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Future Oncol. 2021 Dec;17(34):4657-4663. doi: 10.2217/fon-2021-0952. Epub 2021 Nov 15.

  PMID: 34775804 DERIVED

Related Links

• CSP Redacted
• SAP Redacted
• CSR synopsis Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Dr Andrea Riccardo Filippi

  Fondazione IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: January 30, 2020
• Study Start: November 26, 2020
• Primary Completion: March 30, 2023
• Study Completion: November 25, 2024
• Last Updated: January 10, 2025
• Results First Posted: September 25, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified 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.

Locations

IT (12); PL (5); FR (5); RU (3); ES (7); US (3)