A Study of Durvalumab Before and After Surgery for Patients with Operable Non-Small Cell Lung Cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Feb 2019 → ongoing

Decision date (initial)

2024-08-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509576-42-00

EudraCT number

2018-002997-29

ClinicalTrials.gov

NCT03800134

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of durvalumab + chemotherapy administered prior To surgery followed by durvalumab post-surgery compared with placebo + chemotherapy administered prior To surgery followed by placebo post-surgery in terms of EFS.

To compare the activity of durvalumab + chemotherapy administered prior To surgery compared with placebo + chemotherapy administered prior To surgery in terms of pCR.

Secondary objectives 6

1. To compare the efficacy of perioperative durvalumab + neoadjuvant chemotherapy compared with placebo + neoadjuvant chemotherapy in terms of DFS.
2. To compare the efficacy of perioperative durvalumab + neoadjuvant chemotherapy compared with placebo + neoadjuvant chemotherapy in terms of MPR.
3. To compare the efficacy of perioperative durvalumab + neoadjuvant chemotherapy compared with placebo + neoadjuvant chemotherapy in terms of OS.
4. To compare the efficacy of perioperative durvalumab + neoadjuvant chemotherapy compared with placebo + neoadjuvant chemotherapy in patients with PD-L1 TC ≥1% tumors in terms of EFS, pCR, DFS, MPR and OS.
5. To assess disease-related symptoms and HRQOL in patients treated with perioperative durvalumab + neoadjuvant chemotherapy compared with placebo + neoadjuvant chemotherapy.
6. To assess the PK and immunogenicity of durvalumab.

Conditions and MedDRA coding

Patients with resectable Non-small Cell Lung Cancer (Stage IIA to IIIB; either squamous or non-squamous).

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share 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 Vivli.org. All requests 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age ≥18 years.
2. Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease.
3. World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment.
4. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline.
5. No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines.
6. Adequate organ and marrow function.
7. Confirmation of a patient's tumour PD-L1 status.
8. Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status.
9. Planned surgery to be performed need to include lobectomy, sleeve resection or bilobectomy.
10. A pre- or post-bronchodilator FEV of 1.0 L and >40% post-operative predicted value.

Exclusion criteria 13

1. History of allogeneic organ transplantation.
2. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome).
3. History of another primary malignancy.
4. History of active primary immunodeficiency.
5. Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus.
6. Deemed unresectable NSCLC by multidisciplinary evaluation.
7. Patients who have preoperative radiotherapy treatment as part of their care plan.
8. Patients who have brain metastases or spinal cord compression.
9. Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC.
10. Known allergy or hypersensitivity to any of the study drugs or excipients.
11. Existence of more than one primary tumour such as mixed small cell and NSCLC histology.
12. Patients who are candidates to undergo only pneumonectomy, segmentectomies or wedge resections.
13. Patients with a documented test result confirming the presence of EGFRm or ALK translocation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Event-free Survival (EFS) and pathological Complete Response (pCR) in modified intent-to-treat (mITT).

Secondary endpoints 7

1. DFS in the modified resected population.
2. mPR (≤10% viable tumour cells in lung primary tumour after complete evaluation in the resected lung cancer specimen).
3. OS.
4. EFS, pCR, DFS, mPR, OS in the population with PD-L1 TC ≥1%.
5. Change from baseline in Patient reported outcomes and time to deterioration.
6. Concentration of durvalumab.
7. Presence of ADAs for durvalumab.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

9 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications