Personnalized Immunotherapy in Patients With Stage III Non-small Cell Lung Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorIntergroupe Francophone de Cancerologie Thoracique
About this trial
The reference treatment for locally advanced (stage III) non-small cell lung cancer (NSCLC) is concomitant chemoradiotherapy (CRT) followed by durvalumab consolidation for 1 year. This strategy is based on the results of the PACIFIC trial, which compared, in a randomized fashion after CRT, the superiority of treatment with durvalumab at a dose of 1500 mg every 4 weeks for 12 months to placebo in patients with non-progressive disease. The coprimary endpoints of this trial were progression-free survival (PFS) and overall survival (OS). This study was positive and showed a benefit in PFS and OS. However, less than half of patients (49%) received the full 12 months of durvalumab in this study, one-third of these discontinuations being related to toxicity. Furthermore, the prescription of durvalumab in this setting is not currently guided by any companion biomarker. As a result, the systematic prescription of a 12-month consolidation immunotherapy after CRT, without any selection criteria, leads to a possible overtreatment of patients whose survival would have been prolonged without additional treatment. These patients are systematically exposed to a potentially high and serious risk of toxicity in the course of immunotherapy. It is therefore crucial to move towards a more individualized approach in the prescription of consolidation immunotherapy after CRT in stage III NSCLC. This would ensure that the most appropriate treatment is delivered to patients who are likely to derive significant clinical benefit, while concurrently minimizing the exposure of other patients to potentially severe clinical toxicities. Additionally, such an approach would help protect healthcare systems from unnecessary economic burden, preventing the allocation of resources to treatments that offer limited therapeutic value.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care. Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
Age ≥18 years.
ECOG Performance Status of 0 or 1.
Histologically proven unresectable locally advanced stage III NSCLC.
Disqualifiers
Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R or L861X mutations in exon 21, G719A/S mutation in exon 18, exon 20 insertion) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation).
Known ALK, ROS1, gene rearrangement as assessed by immunohistochemistry, FISH or NGS (ADN or ARN) sequencing by local genetics and/or pathology laboratory.
Sequential CRT, defined as the start of thoracic irradiation after the administration of the third course of chemotherapy.
Pleural involvement or extra-thoracic tumor lesions.
Trial design
Design model
Parallel
Treatments tested in this trial
CAPP-Seq technique
Diagnostic testPatients in Arm B will be divided into 2 groups : MRD positive and MRD negative depending on the result of the CAPP-Sequ technique.
Durvalumab
DrugPatients in Arm A (non-comparative control) will receive durvalumab treatment. The patients in Arm B who are MRD positive (see CAPP-Seq technique intervention) will receive durvalumab treatment.
Treatment groups
177 Participants
are divided into 2 treatment groupsGroup A: Arm A : durvalumabOther 1 intervention
Group B: Arm B : durvalumab or no treatmentExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
To evaluate the efficacy of a personalized strategy of consolidation immunotherapy based on the assessment of MRD post-CRT in stage III NSCLC.
12-month PFS rate from randomization as assessed by an independent review committee (IRC). The primary endpoint is 12-month progression free survival (PFS). The analysis will be conducted in the FAS population. PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by an IRC, or death due to any cause, whichever occurs first.
Time frame
12 months after randomisation.Secondary outcomes
1
PFS as assessed by the investigator
PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by investigator, or death due to any cause, whichever occurs first.
Time frame
Around 54 months2
Overall Survival (OS)
OS is defined as the time from date of randomization to the date of death due to any cause.
Time frame
Around 54 months.3
Tolerance and safety
Incidence, nature, and severity of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0 (NCI CTCAE v6.0).
Time frame
From time of informed consent through end of therapeutic period (consolidation treatment or no consolidation treatment) and up to 90 days after (maximum of 1 year and 3 months).4
Time until definitive HRQoL deterioration (TUDD)
For the symptom scale "Global health status/QOL" of questionnaire QLQ-C30, TUDD is defined as the time from inclusion until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the subject withdraws from therapy or receives another anticancer therapy prior to symptom deterioration.
Time frame
Around 54 monthsSponsors and contacts
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Source ClinicalTrials.gov
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