Study of durvalumab or placebo administered with radiation therapy for patients with early stage non-small cell lung cancer Study of osimertinib administered after radiation therapy in patients with early stage non-small cell lung cancer harboring an EGFR mutation

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

23 Apr 2019 → ongoing

Decision date (initial)

2024-06-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512667-31-00

EudraCT number

2018-002572-41

ClinicalTrials.gov

NCT03833154

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Applicable to main cohort:
To assess the efficacy of durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS in patients with a subset of T1 to T3N0M0 NSCLC

Applicable to osimertinib cohort:
To assess the efficacy of osimertinib following SoC SBRT in patients with T1 to T3N0M0 in terms of 4-year PFS

Secondary objectives 10

1. (Applicable to main cohort) To assess the efficacy of durvalumab with SBRT (Stereotactic Body Radiation Therapy) compared to placebo with SBRT in terms of: PFS in patients with T1 to T3N0M0 NSCLC
2. (Applicable to main cohort) To assess the efficacy of durvalumab with SBRT (Stereotactic Body Radiation Therapy) compared to placebo with SBRT in terms of Overall Survival
3. (Applicable to main cohort) To assess the efficacy of durvalumab with SBRT (Stereotactic Body Radiation Therapy) compared to placebo with SBRT in terms of PFS24, TTP, TTDM, and PFS2
4. (Applicable to main cohort) To assess the PK of durvalumab
5. (Applicable to main cohort) To investigate the immunogenicity of durvalumab
6. (Applicable to main cohort) To assess symptoms and health-related quality of life in patients treated with durvalumab with SBRT compared to placebo with SBRT using the EORTC QLQ-C30
7. (Applicable to main cohort) To assess the safety and tolerability profile of durvalumab with SoC SBRT compared to placebo with SoC SBRT
8. (Applicable to osi cohort) PFS by ICR according to RECIST 1.1
9. (Applicable to osi cohort) OS, TTP, Time to CNS progression, PFS2
10. (Applicable to osi cohort) To assess the safety, tolerability, and compliance of a maximum of 3 years of osimertinib following SoC SBRT

Conditions and MedDRA coding

Main cohort: Patients with unresected Stage I/II, lymph-node negative Non-small Cell Lung Cancer Osimertinib cohort: Open-label, Single arm for patients with unresected stage I/II, lymph done negative NSCLC harboring a sensitizing EGFR mutation

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

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. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. (Applicable to both cohorts) Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling and analyses
2. (Applicable to both cohorts) Age ≥18 years
3. (Applicable to both cohorts) Histologically or cytologically documented Stage I to II NSCLC, with clinical T1 to T3N0M0 Stage I/II disease and planned to receive definitive treatment with SBRT (Stereotactic Body Radiation Therapy). Patients may be medically inoperable or are medically operable and refusing surgery or choosing to have SBRT (Stereotactic Body Radiation Therapy) as definitive therapy
4. (Applicable to both cohorts) Planned SoC SBRT as definitive treatment
5. (Applicable to both cohorts) World Health Organization (WHO)/ECOG PS of 0, 1, or 2
6. (Applicable to both cohorts) Patients with central or peripheral lesions are eligible
7. (Applicable to both cohorts) Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
8. (Applicable to both cohorts) Staging studies must be done during screening (PET-CT within 10 weeks)
9. (Applicable to both cohorts) Submission of available tumor tissue or cell block samples from FNA
10. (Main cohort (durvalumab) specific) Life expectancy of at least 12 weeks
11. (Main cohort (durvalumab) specific) Body weight >30 kg
12. (Main cohort (durvalumab) specific) Adequate organ and marrow function required
13. (Main cohort (durvalumab) specific) Pulmonary Function Testing within 16 weeks of randomization
14. (Osimertinib cohort specific) Confirmation by local laboratory that the tumor harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
15. (Osimertinib cohort specific) Adequate bone marrow reserve or organ function required

Exclusion criteria 12

1. (Applicable to both cohorts) Mixed small cell and non-small cell cancer
2. (Applicable to both cohorts) History of another primary malignancy with exceptions
3. (Main cohort specific) Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
4. (Main cohort specific) History of allogeneic organ transplantation
5. (Main cohort specific) History of active primary immunodeficiency or autoimmune disorders
6. (Main cohort specific) History of non-infectious pneumonitis requiring steroids
7. (Main cohort specific) Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
8. (Main cohort specific) Prior exposure to immune-mediate therapy
9. (Osimertinib cohort specific) Patients currently receiving potent inducers of CYP3A4
10. (Osimertinib cohort specific) Patients with known or increased risk factor for QTc prolongation
11. (Osimertinib cohort specific) Treatment with any of the following: Preoperative or adjuvant platinum-based or other chemotherapy for the disease under investigation; Prior treatment with neoadjuvant or adjuvant EGFR TKI; Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4; Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib
12. (Osimertinib cohort specific) Any of the following cardiac criteria: Mean resting corrected QT interval >470 msec, obtained from 3 ECGs; Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.; Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained -sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval; Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Applicable to main cohort: PFS in patients with subset of T1 to T3N0M0 by BICR
2. Applicable to osimertinib cohort: 4-years PFS by ICR using RECIST 1.1

Secondary endpoints 2

1. Applicable to main cohort: PFS in patients with T1 to T3N0M0 NSCLC; Overall Survival; PFS24, TTP, and TTDM using BICR assessments according to RECIST 1.1; PFS2 using local assessment; PK of durvalumab in serum; Presence of ADA for durvalumab; EORTC QLQ-C30: Change in symptoms, functioning, and global health status/quality of life; Safety and tolerability:AEs, physical examinations, vital signs, electrocardiograms, and laboratory findings
2. Applicable to osimertinib cohort: AEs (graded by CTCAE version 5); Laboratory studies: chemistry, hematology, and urinalysis; Clinical evaluations; ECG parametres; LVEF; WHO performance status; PFS using RECIST 1.1; OS; Site(s) of disease progression; Time to CNS progression; TTP; PFS2

Investigational products

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

Test 3

Placebo 1

Auxiliary 2

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

8 EU/EEA countries · 57 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 77 files

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

Application history

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