Phase III Study to Determine Efficacy of Durvalumab in Stage II-III Non-small Cell Lung Cancer (NSCLC) After Curative Intent Therapy.

NCT04642469 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: D910MC000012020-000612-30
• Study Type: interventional
• Target: 30
• Locations: 25 countries
• Sites: 115

Brief Summary

This is a Phase III double-blind, placebo-controlled study of Durvalumab versus Placebo in patients with stage II-III NSCLC who are MRD-positive following curative intent therapy.

Conditions

Carcinoma, Non- Small Cell Lung

Keywords

NCSLC; Double-blind; PD-L1; MEDI4736; Durvalumab; DFS; OS; MRD+; Lung cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free Survival (DFS)

  DFS was defined as the time from the date of randomization until any one of the following events, whichever occurred first: Date of disease recurrence using Investigator assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 OR Date of death from any cause.

  Every 8 weeks (q8w) ± 1 week until Week 48, then every 12 weeks (q12w) ± 1 week until appearance of RECIST 1.1-defined disease recurrence or follow-up, up to 16.6 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From start of study treatment (Day 1) up to 90 days after last dose of study treatment, approximately 21.4 months

Study Arms (2)

Durvalumab

EXPERIMENTAL

Intravenous administration of Durvalumab

Drug: Durvalumab

Placebo

PLACEBO COMPARATOR

Intravenous administration of placebo

Other: Placebo

Interventions

Durvalumab DRUG

Intravenous administration of Durvalumab

Also known as: Medi4736

Durvalumab

Placebo OTHER

Placebo Comparator

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICFs and in the protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses.
• Provision of signed and dated written optional genetic informed consent prior to collection of the optional sample for genetic analysis. This consent should be signed at the time of second screening. This optional sample and analyses are separate from the mandatory genetic testing consent included in ICF1.
• The following criteria must have been met at the time of surgery or at the time of the curative intent therapy (first screening):
• Age ≥18 years at the time of screening (ICF1);
• Male and/or female
• Histologically confirmed NSCLC with resectable stage II-III disease who have undergone curative intent therapy (complete resection of the primary tumor ± neoadjuvant and/or adjuvant therapy) per SoC.
• Select stage IIIB (ie, T3N2 or T4N2) patients will be eligible, provided they are upstaged to T3N2 or T4N2 based on confirmed pathology after surgery. Patients who are staged as T3N2 or T4N2 prior to surgery are not eligible.
• A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and adrenal glands) along with brain MRI (preferred) or brain CT with IV contrast must have been done for surgical planning prior to surgery. It is recommended that patients undergo combined FDG-PET (18F-Fluoro-deoxyglucose positron emission tomography) and CT scan (computerized tomography) within the 6 weeks prior to surgery in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery. If the positron emission tomography (PET) scan was not performed, or data from a PET is not available, patients may still be enrolled into the study provided appropriate imaging (CT/MRI) is performed prior to randomization.
• Complete resection of the primary NSCLC is mandatory. Invasive (pre-operative or intra-operative) exploration of hilar and mediastinal lymph nodes must have been performed to confirm primary tumor nodal status (prior to or after surgery). Surgical resection of the primary NSCLC can occur by open thoracotomy or by video-assisted thoracic surgery (VATs) and resection can be achieved by segmentectomy, lobectomy, sleeve resection, bilobectomy or pneumonectomy. Patients undergoing wedge resection are not eligible for this study.
• Criteria for prior systemic chemotherapy/radiotherapy:
• Patients should have completed (or be undergoing) curative intent therapy (surgery ± neoadjuvant and/or adjuvant therapy; adjuvant therapy can include PORT) with exceptions noted below:
• Patients who discontinue chemotherapy and/or PORT for toxicity prior to completion of all planned therapy are eligible.
• Patients who have not received any neoadjuvant and/or adjuvant chemotherapy, and meet all other eligibility criteria, may be eligible under the following circumstances:

You may not qualify if:

• Diagnostics assessments:
• EGFR and/or ALK mutant as assessed either from the tumor biopsy taken prior to surgery or the resected tumor tissue. Testing must be performed using a wellvalidated, local regulatory-approved test. EGFR/ALK may be tested centrally if local testing is unavailable.
• Mixed small cell and NSCLC histology.
• Require re-resection or are deemed to have unresectable NSCLC by amultidisciplinary evaluation that must include a thoracic surgeon who performs lung cancer surgery as a significant part of their practice.
• Medical conditions
• History of allogeneic organ or bone marrow transplantation.
• Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample collection
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or
• Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in-situ without evidence of disease
• History of active primary immunodeficiency
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B virus (HBV) (known positive HBV surface antigen (HBsAg) result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Known allergy or hypersensitivity to any of the IPs or any of the IP excipients Prior/concomitant therapy

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (115)

Research Site

Long Beach, California, 90806, United States

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Los Angeles, California, 90089, United States

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Daytona Beach, Florida, 32117, United States

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Gainesville, Florida, 32605, United States

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Punta Gorda, Florida, 33980, United States

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Louisville, Kentucky, 40241, United States

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Minneapolis, Minnesota, 55404, United States

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Spartanburg, South Carolina, 29303, United States

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Nashville, Tennessee, 37203, United States

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Salt Lake City, Utah, 84112, United States

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Buenos Aires, C1125ABD, Argentina

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Camperdown, 2050, Australia

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Melbourne, 3000, Australia

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St Leonards, 2065, Australia

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Hasselt, 3500, Belgium

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Roeselare, 8800, Belgium

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Barretos, 14784-400, Brazil

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Florianópolis, 88034-000, Brazil

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Porto Alegre, 90610-000, Brazil

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São José do Rio Preto, 15090-000, Brazil

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Vitória, 29043-260, Brazil

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Victoria, British Columbia, V8R 6V5, Canada

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Saint John, New Brunswick, E2L 4L2, Canada

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Kingston, Ontario, K7L 2V7, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Olomouc, 77900, Czechia

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Ostrava, 703 00, Czechia

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Prague, 128 08, Czechia

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Marseille, 13915, France

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Pessac, 33604, France

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Saint-Herblain, 44805, France

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Strasbourg, 67091, France

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Athens, 11526, Greece

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Athens, 11527, Greece

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Heraklion, 71110, Greece

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Holargos, Athens, 155 62, Greece

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Larissa, 41110, Greece

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Thessaloniki, 54645, Greece

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Hong Kong, Hong Kong

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Jordan, Hong Kong

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Budapest, 1083, Hungary

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Budapest, 1121, Hungary

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Gyöngyös - Mátraháza, 3200, Hungary

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Győr, 9024, Hungary

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Székesfehérvár, 8000, Hungary

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Szolnok, 5004, Hungary

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Törökbálint, 2045, Hungary

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Bengaluru, 560099, India

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New Delhi, 11029, India

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Haifa, 31096, Israel

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Jerusalem, 91120, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 52621, Israel

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Meldola, 47014, Italy

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Milan, 20133, Italy

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Monza, 20052, Italy

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Orbassano, 10043, Italy

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Roma, 00144, Italy

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Rozzano, 20089, Italy

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Bunkyō City, 160-0023, Japan

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Hiroshima, 734-8551, Japan

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Kashiwa, 277-8577, Japan

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Kōtoku, 135-8550, Japan

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Osaka, 534-0021, Japan

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Osaka, 541-8567, Japan

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Sakaishi, 591-8555, Japan

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Sendai, 980-0873, Japan

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Sunto-gun, 411-8777, Japan

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Yokohama, 241-8515, Japan

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Breda, 4818 CK, Netherlands

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Maastricht, 6202 AZ, Netherlands

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Zwolle, 8025 AB, Netherlands

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Lima, Lima 32, Peru

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Lima, LIMA 34, Peru

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Bydgoszcz, 85-796, Poland

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Gdansk, 80-214, Poland

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Tomaszów Mazowiecki, 97-200, Poland

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Warsaw, 02-781, Poland

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Moscow, 105229, Russia

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Moscow, 115478, Russia

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Novosibirsk, 630108, Russia

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Saint Petersburg, 191036, Russia

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Saint Petersburg, 197758, Russia

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Singapore, 119228, Singapore

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Singapore, 169610, Singapore

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Singapore, 308433, Singapore

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Cheongju-si, 28644, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Suwon, 16247, South Korea

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Barcelona, 08035, Spain

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Barcelona, 08041, Spain

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Madrid, 28041, Spain

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Málaga, 29010, Spain

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Oviedo, 33011, Spain

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Pamplona, 31008, Spain

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Santiago de Compostela, 15706, Spain

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Chiayi City, 613, Taiwan

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Kaohsiung City, Taiwan

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Taichung, 40201, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 11217, Taiwan

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Taipei, 235, Taiwan

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Taoyuan District, 333, Taiwan

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Adana, 01120, Turkey (Türkiye)

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Ankara, 06010, Turkey (Türkiye)

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Istanbul, 34010, Turkey (Türkiye)

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Istanbul, 34214, Turkey (Türkiye)

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Malatya, 44280, Turkey (Türkiye)

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Hanoi, 100000, Vietnam

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Ho Chi Minh City, 70000, Vietnam

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Hochiminh, 70000, Vietnam

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Related Links

• Redacted CSP
• Redacted SAP
• Redacted CSR synopsis

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The Sponsor closed enrollment to the study early due to treatment landscape changes. Interpretation of study outcomes were limited by the resulting small sample size and limited duration of follow-up.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• David Spigel

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

• Charles Swanton

  Francis Crick Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind and open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 24, 2020
• Study Start: November 30, 2020
• Primary Completion: May 31, 2023
• Study Completion: January 15, 2024
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-05

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

TU (5); ES (7); CZ (3); AU (3); GR (6); IN (2); IL (5); NL (3); CA (5); TW (7); VN (3); BR (5); US (10); FR (4); HU (7); IT (6); JP (10); PE (2); RU (5); AR (1); BE (2); HK (2); PL (4); SG (3); KR (5)