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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04642469




Registration number
NCT04642469
Ethics application status
Date submitted
3/11/2020
Date registered
24/11/2020
Date last updated
15/03/2024

Titles & IDs
Public title
Phase III Study to Determine Efficacy of Durvalumab in Stage II-III Non-small Cell Lung Cancer (NSCLC) After Curative Intent Therapy.
Scientific title
A Phase III, Randomized, Multicenter, Double-blind, Placebo-controlled Study of Durvalumab for the Treatment of Stage II-III NSCLC Patients With Minimal Residual Disease Following Surgery and Curative Intent Therapy.
Secondary ID [1] 0 0
2020-000612-30
Secondary ID [2] 0 0
D910MC00001
Universal Trial Number (UTN)
Trial acronym
MERMAID-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non- Small Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Other interventions - Placebo

Experimental: Durvalumab - Intravenous administration of Durvalumab

Placebo Comparator: Placebo - Intravenous administration of placebo


Treatment: Drugs: Durvalumab
Intravenous administration of Durvalumab

Other interventions: Placebo
Placebo Comparator
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the efficacy of durvalumab compared to placebo as measured by DFS in all randomized patients. Outcomes measures were adjusted to align with the previous version of the protocol except for the changes according to the protocol amendment.
Timepoint [1] 0 0
Approximately 2 years.
Secondary outcome [1] 0 0
To assess the safety and tolerability profile of durvalumab monotherapy compared with placebo. Outcomes measures were adjusted to align with the previous version of the protocol except for the changes according to the protocol amendment.
Timepoint [1] 0 0
Approximately 2 years.

Eligibility
Key inclusion criteria
Informed consent

1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the ICFs and in the protocol.

2. Provision of signed and dated, written informed consent form prior to any mandatory
study-specific procedures, sampling, and analyses.

3. 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):

4. Age =18 years at the time of screening (ICF1);

5. Male and/or female

6. 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.

7. 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.

8. 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:

9. 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:

- All patients who are eligible for adjuvant chemotherapy MUST be offered adjuvant
chemotherapy.

- The patient has declined adjuvant chemotherapy, and in the opinion of the
Investigator, this is the patient's final decision after receiving appropriate
information and adequate time to make the decision. The patient's refusal of
adjuvant chemotherapy must be documented.

- If in the view of the Investigator, adjuvant chemotherapy is contraindicated due
to an underlying intercurrent illness/laboratory abnormality, which is not
considered reversible within a reasonable timeframe for the patient to be
eligible for adjuvant therapy, which must be documented.

Criteria assessed prior to and at the start of surveillance:

10. Confirmation of suitable biosamples for WES and central PD-L1 testing. Resected tumor
tissue and whole blood samples must be provided to the diagnostic laboratory for WES
of tumor and germline DNA, respectively as soon as possible following pathology
confirmation. Samples must be sent no later than 1-2 weeks after completion of
adjuvant therapy or 3-5 weeks after surgery (if no adjuvant therapy is given) for
development of the Sponsor-approved personalized panel for MRD detection at a central
reference laboratory. Germline sequencing of whole blood is mandatory. Resected tumor
tissue must also be provided for PD-L1 testing at a central reference laboratory (see
inclusion criteria 15).

11. Post-adjuvant therapy or post-surgery (if no adjuvant therapy is given) CT scan of the
chest and abdomen (including liver and adrenal glands) and brain MRI [preferred] or
brain CT with IV contrast should be available to confirm no evidence of metastasis. If
scans were not performed post-curative intent therapy, additional scans must be done
prior to start of surveillance.

12. Consents to be accessible for q6w±3d plasma sample collection for MRD evaluation and
for q12w±1w CT scans during the 96-week surveillance period.

13. The plasma sample that marks the start of surveillance must be collected 8±1 weeks
after completion of adjuvant therapy (if administered) or 12±1 weeks after surgery
(where adjuvant therapy is not given).

- A patient who is determined to be MRD- based on analysis of this plasma sample
(ie, MRD- at the start of surveillance) may continue in surveillance provided all
other eligibility criteria are met.

- A patient who is determined to be MRD+ based on analysis of this plasma sample
(ie, MRD+ at the start of surveillance) may be eligible for immediate
randomization provided all other eligibility criteria are met.

A patient who becomes MRD+ during surveillance is eligible to enter the second
screening period and may be randomized in the study if all other eligibility criteria
are met.

Criteria for second screening prior to randomization to treatment:

14. CT scan of the chest and abdomen (including liver and adrenal glands) and brain MRI
[preferred] or brain CT with IV contrast performed within the 28 days ± 7 days prior
to randomization to confirm no evidence of RECIST 1.1-defined disease recurrence
and/or metastasis.

15. Known tumor PD-L1 status determined at a central reference laboratory testing service
using a validated Ventana SP263 PD-L1 immunohistochemistry (IHC) assay prior
randomization. Patients with unknown PD-L1 status are not eligible for the study.

16. WHO/Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

17. Complete post-operative wound healing must have occurred prior to randomization;
patients must have recovered from all acute, reversible toxic effects from prior
treatments (excluding alopecia) that could potentially adversely impact further
administration of durvalumab/placebo according to the Investigator's judgment.

18. Must have recovered from all acute, reversible toxic effects from chemotherapy that
could potentially adversely impact further administration of durvalumab or placebo
according to the Investigator's judgment

19. Adequate organ and marrow function as described in the protocol.

20. Must have a life expectancy of at least 12 weeks Weight

21. Body weight >30 kg Inclusion criteria assessed prior to entering the observation
period

22. No evidence of RECIST 1.1-defined disease recurrence or metastasis confirmed by CT
scan of the chest and abdomen (including liver and adrenal glands) and a brain MRI
(preferred) or brain CT with IV contrast.

23. MRD- status, as determined by testing the last plasma sample collected during the
96-week surveillance period.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnostics assessments:

1. 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.

2. Mixed small cell and NSCLC histology.

3. 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.

4. Baseline imaging demonstrating unequivocal evidence of RECIST 1.1-defined disease
recurrence or evidence of clinical recurrence outside of imaging prior to
randomization. In the event of lymphadenopathy on imaging that would lead to
exclusion, histopathological confirmation of lymph node metastasis should be obtained
prior to excluding a patient from the study. If pathological confirmation of lymph
node metastasis is not technically feasible and imaging appearance are deemed
unequivocal for relapse, the patient will be excluded.

Medical conditions

5. History of allogeneic organ or bone marrow transplantation.

6. Non-leukocyte-depleted whole blood transfusion in 120 days of genetic sample
collection

7. 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

8. 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.

9. 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

10. History of active primary immunodeficiency

11. 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.

12. Known allergy or hypersensitivity to any of the IPs or any of the IP excipients
Prior/concomitant therapy

13. Received any IO therapy in the adjuvant setting or any prior exposure to durvalumab.

14. Received any radiotherapy in the neoadjuvant setting.

15. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone
replacement therapy) is acceptable.

16. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of IP.

17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30
days after the last dose of IP.

18. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
first dose of IP.

19. Current or prior use of immunosuppressive medication within 14 days before the first
dose of IP. The following are exceptions to this criterion:

Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intra-articular injection) Systemic corticosteroids at physiologic doses not to exceed
10 mg/day of prednisone or its equivalent Steroids as premedication for
hypersensitivity reactions (eg, CT scan premedication) Prior/concurrent clinical study
experience

20. Previous IP assignment in the present study

21. Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study

22. Prior randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.

Other exclusions

23. Female patients who are pregnant or breastfeeding.

- Female patients who become pregnant during the study will be withdrawn from
surveillance and are not eligible for randomization.

24. Male or female patients of reproductive potential who are not willing to employ
effective birth control at the time of entry into second screening (initiated with the
signing of ICF2a) until 90 days after the last dose of IP (See Appendix H).

25. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/01/2024
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment outside Australia
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United States of America
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California
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Florida
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Kentucky
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Minnesota
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South Carolina
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Tennessee
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United States of America
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Utah
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Argentina
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Buenos Aires
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Belgium
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Hasselt
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Belgium
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Roeselare
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São José do Rio Preto
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Vitoria
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British Columbia
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Canada
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New Brunswick
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Olomouc
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Czechia
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Ostrava
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Czechia
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Praha 2
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France
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Marseille
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France
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Pessac
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France
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France
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Greece
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Athens
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Greece
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Heraklion
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Greece
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Holargos, Athens
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Greece
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Larissa
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Greece
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Thessaloniki
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Hong Kong
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Hong Kong
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Hong Kong
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Jordan
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Hungary
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Budapest
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Hungary
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Gyöngyös - Mátraháza
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Hungary
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Gyor
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Hungary
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Szolnok
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Hungary
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Székesfehérvár
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Hungary
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Törökbálint
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India
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Bengaluru
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India
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New Delhi
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petah Tikva
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Israel
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Ramat-Gan
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Italy
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Meldola
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Italy
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Milano
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Italy
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Monza
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Italy
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Orbassano
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Italy
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Roma
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Italy
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Rozzano
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Japan
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Bunkyo-ku
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Hiroshima-shi
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Japan
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Kashiwa
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Japan
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Koto-ku
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Japan
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Osaka-shi
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Japan
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Sakai-shi
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Japan
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Sendai-shi
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Japan
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Sunto-gun
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Japan
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Yokohama-shi
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Korea, Republic of
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Cheongju-si
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Korea, Republic of
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Seoul
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Korea, Republic of
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Suwon
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Netherlands
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Breda
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Netherlands
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Maastricht
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Netherlands
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Zwolle
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Peru
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Lima
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Poland
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Bydgoszcz
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Gdansk
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Poland
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Tomaszów Mazowiecki
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Warszawa
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Russian Federation
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Moscow
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Russian Federation
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Novosibirsk
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Russian Federation
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Saint Petersburg
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Singapore
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Singapore
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Barcelona
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Madrid
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Málaga
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Spain
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Oviedo
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Spain
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Pamplona
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Spain
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Santiago de Compostela
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Taiwan
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Chiayi
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Tao-Yuan
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
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Turkey
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Malatya
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Vietnam
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Hanoi
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Vietnam
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Ho Chi Minh
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Vietnam
State/province [95] 0 0
Hochiminh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04642469
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Spigel
Address 0 0
SCRI Development Innovations, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04642469