A multicentre single arm phase II trial assessing the efficacy of immunotherapy, chemotherapy and stereotactic radiotherapy to metastases followed by definitive surgery or radiotherapy to the primary tumour, in patients with synchronous oligo-metastatic nonsmall cell lung cancer

In this phase II study, we examine a small number of patients with non-small
cell lung cancer to test the efficacy of the new combination therapy
(durvalumab and tremelimumab, combined with chemotherapy and radiotherapy)
(evaluation of the progression-free survival). Most patients with non-small
cell lung cancer are excluded from immunotherapy (such as durvalumab and
tremelimumab) as the first choice of treatment. Various strategies are
currently being developed to improve treatment results. Immunotherapy is
promising to be combined with standard chemotherapy and radiotherapy.

This study has been transitioned to CTIS with ID 2024-511134-12-00 check the CTIS register for the current data.

The objective of this trial is to evaluate progression-free survival in
synchronous oligometastatic NSCLC patients treated with induction
immunotherapy, chemotherapy and SBRT to all metastases followed by definitive
surgery or radiotherapy to the locoregional primary tumour.

In the first part of the study, all patients receive standard chemotherapy (4
to 6 cycles) plus radiotherapy of the metastases. In addition to this standard
care, the patients receive the research drugs durvalumab and tremelimumab
(immunotherapy) at the same time as they receive chemotherapy for 4 cycles.
A FDG / PET / CT scan is performed after three months to assess the status of
the lung cancer. With this test, very small changes in cell function are
visible, caused by the growth of cancer cells.
All patients whose lung cancer has remained stable or has decreased in size
will undergo either surgery or radiation therapy of the lung cancer. Durvalumab
will be given for a maximum of one year (from the start of durvalumab) or until
disease progression. Tremelimumab will be given once more on day 1 of cycle 7
(5 infusions in total)
In patients whose lung cancer has not remained stable or has increased at the
time of the PDG / PET / CT scan, the study treatment will stop. Those patients
can move on to the follow-up phase of the study. Other therapies will be
discussed and the survival and worsening of the disease will be assessed.
The main focus of the ETOP 14-18 CHESS trial is the definitive treatment of the
primary tumour by either complete resection by surgery or definitive
radiotherapy.The trial is of curative intent and it is therefore very unlikely
that continuation of durvalumab beyond 12 months will bring additional benefit
to patient with complete remission after definitive treatment.Patient without
complete remission after completion of the protocol treatment too, are also
very unlikely to derive additional benefit from continuation of durvalumab
treatment beyond the 12 months. These patients will require further line of
treatment. This is outside of the scope of the CHESS trial and should be done
according to best clinical practice based on the local standard of care.

Multicentre single arm phase II interventional trial

All patients will be treated with durvalumab (1500 mg i.v.) and tremelimumab
(75 mg i.v.) every 3 weeks for the first 4 cycles (during chemotherapy)
Patients that have not progressed at the time of restaging (FDG-PET-CT at 3
months from treatment start) will continue with durvalumab treatment
every 3 weeks until chemotherapy has been completed and proceed to definitive
treatment of the primary tumour.
After the completion of chemotherapy, treatment with durvalumab (1500 mg i.v.)
continues every 4 weeks until disease progression or for a maximum of 1 year
from start of induction treatment. Tremelimumab (75 mg i.v.) will be given once
more on day 1 of cycle 7 (5 infusions in total)

- The most common side effects of durvalumab: diarrhea, skin rash/dry itchy
skin, liver problems, fatigue, nausea, vomiting, abdominal pain, fluid
retention that causes swelling, upper respiratory tract infections,
decreased appetite, shortness of breath, cough and fever.
- The most common side effects of durvalumab in combination with tremelimumab
in clinical trials are: perforation of the colon.
- Blood samples can hurt or cause a blood shed. This may increase the risk of
infection.
- There is a risk of an allergic reaction in radiological examinations that
require injection of a contrasting agent.