ETOP 14-18 CHESS: Immunotherapy, chemotherapy and radiotherapy, followed by surgery or radiotherapy, for patients with newly diagnosed non-small cell lung cancer that has spread to a few other parts of the body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

20 Dec 2023 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AG Switzerland

External identifiers

EU CT number

2024-511134-12-00

EudraCT number

2018-003011-22

ClinicalTrials.gov

NCT03965468

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The objective of this trial is to evaluate PFS in synchronous oligo-metastatic NSCLC patients treated with immunotherapy (durvalumab and tremelimumab), chemotherapy and SBRT to all metastases followed by definitive surgery or radiotherapy to the locoregional primary tumour.

Conditions and MedDRA coding

NSCLC, synchronous oligo-metastatic

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Most important inclusion criteria (Cohort 2): • Histologically confirmed NSCLC • Synchronous oligo-metastatic stage IV disease: – maximum of three distant metastases, one of which must be extra-cerebral for SBRT – Initial mediastinal staging is recommended (except for lymph nodes <1 cm on CT and PET-negative) preferentially by endobronchial ultrasound (EBUS) – Neurosurgical resection of one single CNS metastasis or laparoscopic resection of one adrenal metastasis before study inclusion is allowed (one extra-cerebral metastasis must be available for SBRT) • Able to understand and give written informed consent and comply with study procedures • Age ≥18 years • ECOG Performance Status 0-1 • Availability of tumour tissue for translational research • Adequate haematological, renal and liver function

Exclusion criteria 1

1. Most important exclusion criteria (Cohort 2) • Prior chemotherapy, radiotherapy or therapeutic surgery for NSCLC (an exception is the resection of one single CNS or adrenal metastasis, as above) • Activating driver mutation: EGFR, ALK, ROS1 • More than three distant metastases • Brain metastases not amenable for radiosurgery or neurosurgery • Extra cranial metastatic locations such as malignant ascites, pleural or pericardial effusion, diffuse lymphangiosis of skin or lung, diffuse bone marrow metastasis, abdominal masses/abdominal organomegaly, identified by physical exam that is not measurable by reproducible imaging techniques. • Primary lung cancer not suitable for radical therapy (pneumonectomy excluded) • History of leptomeningeal carcinomatosis • Major surgery or significant traumatic injury from which the patient has not recovered at least 28 days before enrolment • Any uncontrolled intercurrent illness, including but not limited to: ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease or serious chronic gastrointestinal conditions associated with diarrhoea, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol • Active tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection • Active autoimmune disease requiring systemic treatment • Severe or uncontrolled cardiac disease requiring treatment • History of primary immunodeficiency • History of allogeneic organ transplant • Receipt of live attenuated vaccines within 30 days prior to enrolment • Known allergies or hypersensitivity to trial drugs or to any excipient. • Sexually active men and women of childbearing potential who are not willing to use a highly effective contraceptive method during the trial and for up to 90 days after last dose of durvalumab monotherapy and up to 180 days after last dose of durvalumab plus tremelimumab combination therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival at 1 year

Secondary endpoints 8

1. Overall survival
2. Pattern of disease progression
3. Distant progression-free survival
4. Response to induction therapy
5. Overall response
6. Duration of response
7. Toxicity before and after surgery/radiotherapy
8. Symptom-specific and global quality of life

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners

Third parties 4

Locations

3 EU/EEA countries · 7 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 29 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