Phase III Study to Determine the Efficacy of Durvalumab in Combination With Chemotherapy in Completely Resected Stage II-III Non-small Cell Lung Cancer (NSCLC)
MERMAID-1
A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Study to Determine the Efficacy of Adjuvant Durvalumab in Combination With Platinum-based Chemotherapy in Completely Resected Stage II-III NSCLC (MERMAID-1)
2 other identifiers
interventional
89
33 countries
140
Brief Summary
This is a Phase III, randomized, parallel-arm, placebo controlled, double blind, multicenter study assessing the efficacy and safety of durvalumab versus placebo following SoC chemotherapy in patients with completely resected stage II-III NSCLC who are MRD+ post surgery
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jul 2020
Typical duration for phase_3
140 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 30, 2020
CompletedFirst Posted
Study publicly available on registry
May 12, 2020
CompletedStudy Start
First participant enrolled
July 17, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2023
CompletedResults Posted
Study results publicly available
August 30, 2024
CompletedAugust 30, 2024
August 1, 2024
3.1 years
April 30, 2020
August 7, 2024
August 7, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Disease-free Survival (DFS) in FAS (Using Investigator Assessments According to Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1])
DFS was defined as the time from the date of randomization until either of the following events, whichever occurred first: disease recurrence using Investigator RECIST 1.1 assessments (i.e., local or regional recurrence, distant recurrence, second primary NSCLC) or death from any cause.
Every 12 weeks (q12w) ± 1 week until appearance of RECIST 1.1-defined disease recurrence or until primary DFS analysis, up to 33.28 months
Secondary Outcomes (3)
DFS in Minimal Residual Disease-positive (MRD+) Analysis Set (Using Investigator Assessments According to RECIST 1.1)
Every 12 weeks (q12w) ± 1 week until appearance of RECIST 1.1-defined disease recurrence or until primary DFS analysis, up to 33.28 months
OS in FAS
From the date of randomization until death due to any cause, up to 35 months
Overall Survival (OS) in MRD+ Analysis Set
From the date of randomization until death due to any cause, up to 35 months
Study Arms (2)
Durvalumab + SoC chemotherapy
EXPERIMENTALIntravenous administration of Experimental and Standard of Care Therapy
Placebo + SoC chemotherapy
PLACEBO COMPARATORIntravenous administration of Placebo and Standard of Care Therapy
Interventions
Experimental Treatment
Eligibility Criteria
You may qualify if:
- Patients must be capable of giving signed informed consent, which includes a mandatory genetic informed consent and compliance with the requirements and restrictions listed in the informed consent forms (ICFs) and in this protocol. Provision of signed and dated, written ICFs must occur prior to any mandatory study-specific procedures, sampling, and analyses.
- In addition to ICF1 and ICF2, patients will provide signed and dated written optional genetic informed consent prior to collection of a sample for optional genetic analysis at the time of second screening (Table 2). This is different from the genetic samples and testing covered by ICF1, which are mandatory for participation in this study.
- Criteria and procedures initiated with the signing of ICF1
- ICF1 must be signed and dated prior to any study procedures and prior to the planned surgical resection of the primary NSCLC, with the exceptions noted below. This consent will cover the study-specific first screening procedures outlined in Table 1.
- Exception: Patients will be permitted to sign ICF1 up to Week 3 (Day 21) postsurgery. Patients identified after Week 3 post-surgery but prior to Week 5 (Day 35) post-surgery may be allowed to sign ICF1 depending on the outcome of the discussion with the study physician. In these cases, a whole blood sample and resected tumor tissue must be collected and sent to the diagnostic lab as soon as possible after ICF1 is signed for development of the personalized panel. A plasma sample must still be collected at Week 3-5 (Day 21-35) post-surgery, even if creation of the personalized panel for MRD detection is delayed.
- Age
- Age ≥18 years at the time of screening. Sex
- Male and/or female. Type of patient and disease characteristics
- Individuals who have diagnosis of histologically confirmed NSCLC (WHO 2015 classification) with resectable (stage II-III) disease (according to IASLC Staging Manual in Thoracic Oncology v8.0). Select (ie, T3N2 or T4N2) stage IIIB patients will be eligible, provided that they are upstaged to T3N2 or T4N2 based on confirmed pathology. Patients who are staged asT3N2 or T4N2 prior to surgery are not eligible.
- A contrast-enhanced CT or MRI scan of the chest 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 (contrastenhanced or low-dose CT component) in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery. In the absence of pre-operative FDG-PET CT imaging, pre-operative contrast-enhanced CT imaging or MRI scan must cover liver and adrenal glands. If only CT is available, or FDG-PET reveals suspicious lymph node mediastinal involvement, it is recommended that invasive pre-operative mediastinal staging is performed according to the algorithm of the European Society of Thoracic Surgeons guidelines (algorithm to follow for primary mediastinal staging if only pre-operative CT is available \[De Leyn et al 2007\], algorithm to follow for primary mediastinal staging when PET-CT is available \[De Leyn et al 2014\]). It is preferred that imaging occurs within 6 weeks prior to surgery. Brain MRI (preferred) or brain CT with IV contrast is required for complete staging of the tumor.
- Complete resection of the primary NSCLC is mandatory. The primary tumor must be deemed resectable by a multidisciplinary evaluation that must include a thoracic surgeon certified or trained according to local standards and who performs lung cancer surgery as a significant part of their practice. 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. Note: Patients undergoing segmentectomy must have tumors less than 2 cm in maximum diameter. Where a resection has been extended by means of a wedge resection of an adjacent lobe to ensure complete resection of a tumor at or crossing a fissure between lobes, this is acceptable if surgical margins are clear of disease. Where the resection of a second tumor nodule (eg, a T4 lesion) is undertaken by means of a wedge resection of a separate lobe, then the patient is not eligible.
- At a minimum, the following parameters should be met for a tumor to be declared completely resected:
- The surgeon performing the resection should remove all gross disease by the end of surgery. All surgical margins of resection must be macroscopically negative for tumor.
- Pathology and/or operative reports must include the examination of at least 2 different mediastinal lymph node (N2) levels, one of which is the subcarinal node-group (level 7) and the second of which is lobe-specific (defined below).
- Note: In the uncommon clinical situation where the surgeon thoroughly examines a mediastinal lymph node level and does not find any lymph nodes, that mediastinal lymph node level may be counted among the minimum 2 required levels. However, the surgeon must clearly document in the operative report or in a separate written statement that the lymph node level was explored and no lymph nodes were present. Normal appearing lymph nodes, if present, must be biopsied or removed. Exploration of nodes must clearly be documented in medical file if not recorded in operative report.
- +16 more criteria
You may not qualify if:
- Diagnostic assessments
- EGFR-mutant and/or ALK-translocation-positive, as assessed either from a pre-surgical biopsy sample (preferred) or the resected tumor tissue (if biopsy was not evaluable or available). Any of the following scenarios are acceptable for this study:
- Where EGFR/ALK results are obtained from a pre-surgical tissue biopsy as part of standard local practice, the patient must be confirmed EGFR/ALK wild-type prior to enrolling in the study.
- Results obtained from testing the patient's primary tumor tissue during screening for another AstraZeneca study may be used in this study.
- Results from local testing of a pre-surgical biopsy. All local EGFR/ALK testing performed locally must be performed using a well-validated, local regulatory-approved test. EGFR/ALK may be tested centrally if local testing is unavailable. Patients will still be allowed to continue with first screening procedures while testing is ongoing but will not be able to continue into second screening if their tumor tests positive for EGFR mutations and/or ALK translocations.
- Mixed small cell and NSCLC histology.
- Require re-resection or are deemed to have unresectable NSCLC by a multidisciplinary evaluation that must include a thoracic surgeon who performs lung cancer surgery as a significant part of their practice.
- Patients who are candidates to undergo only wedge resections. Medical conditions
- History of allogeneic organ or bone marrow transplantation.
- 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
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (140)
Research Site
Birmingham, Alabama, 35294, United States
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Long Beach, California, 90806, United States
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Santa Rosa, California, 95403, United States
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West Hollywood, California, 90048, United States
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Miami, Florida, 33136, United States
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Silver Spring, Maryland, 20910, United States
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Minneapolis, Minnesota, 55407, United States
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Lincoln, Nebraska, 68510, United States
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Albuquerque, New Mexico, 87131, United States
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New York, New York, 10032, United States
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Durham, North Carolina, 27710, United States
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Spartanburg, South Carolina, 29303, United States
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Sioux Falls, South Dakota, 57105, United States
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Houston, Texas, 77090, United States
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Seattle, Washington, 98108-1532, United States
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Rosario, S2000CVB, Argentina
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Camperdown, 2050, Australia
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St Leonards, 2065, Australia
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Aalst, 9300, Belgium
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Brussels, 1200, Belgium
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Hasselt, 3500, Belgium
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Leuven, 3000, Belgium
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Roeselare, 8800, Belgium
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Belo Horizonte, 30110-022, Brazil
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Blumenau, 89010-340, Brazil
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Fortaleza, 60336-045, Brazil
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São José do Rio Preto, 15090-000, Brazil
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São Paulo, 04501-000, Brazil
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Vitória, 29043-260, Brazil
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Panagyurishte, 4500, Bulgaria
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Sofia, 1113, Bulgaria
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Sofia, 1618, Bulgaria
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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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Toronto, Ontario, M5G 2M9, 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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Prague, 140 59, Czechia
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Copenhagen, 2100, Denmark
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Odense C, 5000, Denmark
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Bordeaux, 33000, France
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Marseille, 13915, France
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Saint-Herblain, 44805, France
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Strasbourg, 67091, France
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Toulouse, 31000, France
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Villejuif, 94805, France
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Esslingen am Neckar, 73730, Germany
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Gauting, 82131, Germany
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Regensburg, 93049, Germany
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Athens, 11526, Greece
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Athens, 11527, Greece
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Heraklion, 711 11, Greece
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Holargos, Athens, 155 62, Greece
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Thessaloniki, 54645, Greece
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Hong Kong, Hong Kong
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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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Szolnok, 5004, Hungary
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Törökbálint, 2045, Hungary
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Bengaluru, 560099, India
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Delhi, 110029, India
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Mohali, 160055, India
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Haifa, 3109601, Israel
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Kfar Saba, 95847, Israel
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Petah Tikva, 49100, Israel
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Ramat Gan, 5265601, Israel
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Meldola, 47014, Italy
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Orbassano, 10043, Italy
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Roma, 00144, Italy
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Akashi-shi, 673-8558, Japan
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Bunkyō City, 113-8677, 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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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Osaka, 534-0021, Japan
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Osaka, 541-8567, 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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Culiacán, 80040, Mexico
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México, 01710, Mexico
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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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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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Wroclaw, 53-413, Poland
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Floreşti, 407280, Romania
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Kazan', 420029, Russia
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Krasnodar, 350086, Russia
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Krasnoyarsk, 660133, Russia
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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, 169610, 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, 442-723, South Korea
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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 (A Coruña), 15706, Spain
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Stockholm, 17176, Sweden
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Lausanne, 1011, Switzerland
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Zurich, CH-8091, Switzerland
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Chiayi City, 613, Taiwan
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Taichung, 40201, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 10449, Taiwan
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Taipei, 114, Taiwan
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Taipei, 235, Taiwan
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Taipei, Taiwan
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Taoyuan District, Taiwan
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Bangkok, 10300, Thailand
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Bangkok, 10330, Thailand
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Chiang Mai, 50200, Thailand
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Khon Kaen, 40002, Thailand
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Phisanulok, 65000, Thailand
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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, 44100, Turkey (Türkiye)
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Hanoi, 100000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The sponsor closed enrollment early due to the changes in the treatment landscape. Interpretation of the efficacy results is inconclusive due to the small sample size, resulting in wide confidence intervals, and limited duration of follow-up. The overall safety findings remained consistent with the known safety profiles of durvalumab and SoC chemotherapy. No new safety concerns were identified in this study.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Solange Peters
Centre Hospitalier Universitaire Vaudois (CHUV)
- PRINCIPAL INVESTIGATOR
Charles Swanton
Francis Crick Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- 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
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 30, 2020
First Posted
May 12, 2020
Study Start
July 17, 2020
Primary Completion
August 31, 2023
Study Completion
August 31, 2023
Last Updated
August 30, 2024
Results First Posted
August 30, 2024
Record last verified: 2024-08
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
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