ERICA-02 Study : Impact of Physical Exercise on the Tumor Immune Microenvironment in Patients Treated With Neoadjuvant Chemoimmunotherapy for Non-small Cell Lung Cancer (ERICA-02)

Recent advances combining chemotherapy and immunotherapy before surgery have significantly improved outcomes for patients with resectable non-small cell lung cancer (NSCLC). However, a substantial proportion of patients still do not respond optimally to these treatments. Researchers believe that physical activity may help strengthen the immune system and favorably modify the tumor microenvironment, potentially improving treatment effectiveness. ERICA-02 aims to investigate this hypothesis.The primary objective of ERICA-02 is to evaluate whether a structured exercise program performed during neoadjuvant chemo-immunotherapy can increase the presence of CD8+ cytotoxic T lymphocytes within the tumor. These immune cells play a key role in recognizing and destroying cancer cells and are considered an important marker of anti-tumor immune response.The study is designed for adults with locally advanced, resectable non-small cell lung cancer who are eligible for neoadjuvant chemo-immunotherapy followed by surgery. Participants must be medically fit to engage in physical activity, able to comply with study procedures, and provide informed consent before enrollment.ERICA-02 is a multicenter, randomized phase II pilot trial involving approximately 40 patients. Participants will be randomly assigned to one of two groups : intervention group and control group. Each participant will be involved in the study for approximately six months, including three months of exercise intervention for patients assigned to the exercise group.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Neoplasms; Non Small Cell Lung Cancer
• Intervention / Treatment: Behavioral: Physical activity recommendations; Behavioral: Physical Activity (PA) Intervention

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manon GOUEZ, Phd; Phone Number: 0033451304860; Email: manon.gouez@lyon.unicancer.fr
• Study Contact Backup: Name: Meyssane Djebali, Msc; Phone Number: 003426556743; Email: meyssane.djebali@lyon.unicancer.fr

Study Locations

• France
  • Villefranche-sur-Saône, France
    • Hopitaux Nord Ouest
    • Sub-Investigator: Camille SIMON
    • Contact: HUET; Phone Number: +33 474092385; Email: ahuet@hno.fr
    • Sub-Investigator: Luc Odier
    • Sub-Investigator: Christine Dussopt
    • Sub-Investigator: Lionel Falchero
  • Rhône
    • Lyon, Rhône, France, 69373
      • Centre Léon Berard (CLB)
      • Principal Investigator: Aurelie Swalduz, MD
      • Contact: Aurelie Swalduz; Phone Number: +33 4069856217; Email: aurelie.swalduz@lyon.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients with locally advanced, resectable non-small cell lung cancer (NSCLC), stage IIA (≥ 4 cm) to IIIA according to the TNM classification (American Joint Committee on Cancer, 9th edition)

• PD-L1 positive
• ECOG performance status of 0 or 1 at diagnosis
• Sufficient tumor material for the analyses planned by the study Note: The amount of available material must be validated by the coordinating center before patient enrollment
• With measurable disease according to RECIST version 1.1 criteria
• Recently diagnosed and eligible for neoadjuvant chemotherapy-immunotherapy, as decided by the multidisciplinary tumor board (MTB)
• Having obtained medical certification of fitness to engage in physical activity, issued by the referring oncologist or the principal investigator
• Willing and deemed likely to comply with the intervention and visit schedule and follow-up examinations throughout the duration of the study
• Able to understand, read, and speak French
• Affiliated with a social security scheme
• Having been informed about the study and having signed an informed consent form

Exclusion Criteria:

• Activating EGFR mutations or ALK translocations, as well as those who have received prior chemotherapy, immunotherapy, or radiotherapy for their current lung cancer
• History of cancer within the last 5 years
• Uncontrolled cardiovascular disease, including heart failure, unstable coronary artery disease, severe arrhythmias, or uncontrolled hypertension that could limit participation in physical activity, according to the investigator
• Uncontrolled type 2 diabetes despite appropriate treatment
• Severe limiting pulmonary disease such as GOLD stage IV chronic obstructive pulmonary disease, or severe restrictive lung disease
• Major neuropsychiatric disorders that could hinder participation in the program (e.g., dementia, Alzheimer's disease, advanced Parkinson's disease)
• Severe physical disability or any other medical condition that contraindicates participation in an exercise program • Concurrent participation in another physical activity study
• Pregnant woman
• Person deprived of liberty by judicial or administrative decision, or adult protected by law

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Physical Activity Recommendations	Behavioral: Physical activity recommendations; At the baseline, all participants will receive the international recommendations in terms of physical activity for promoting health in the general population.
Experimental: Supervised Physical Activity Program	Behavioral: Physical activity recommendations; At the baseline, all participants will receive the international recommendations in terms of physical activity for promoting health in the general population.; Behavioral: Physical Activity (PA) Intervention; The exercise programme is carried out during the neoadjuvant period (9 to 12 weeks), alongside the three cycles of chemo-immunotherapy. Participants are provided with an exercise bike and a heart rate monitor. The programme is structured in three progressive phases: adaptation (weeks 1 to 3, light to moderate intensity), progression (weeks 4 to 6, increased intensity and introduction of interval training) and maintenance/optimisation (from week 7 until surgery, stabilisation of the training load). Outside the treatment weeks, participants undertake one supervised strength training session each week via videoconference and two independent aerobic sessions on an exercise bike. During each treatment session (C1, C2, C3), a supervised session combining aerobic exercise and strength training is carried out whilst the infusion is in progress.A weekly telephone follow-up allows the programme to be adjusted and enables the collection of assessments of fatigue and perceived exertion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the effect of a structured exercise program on immune pathological response (irPR)	Impact of structured exercise on the tumor immune microenvironment in patients receiving neoadjuvant chemo-immunotherapy. The primary endpoint is the density of CD8+ cytotoxic T lymphocytes (cells/mm²) within the tumor on the surgical specimen.	T2 (pre-surgery):

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate changes in the tumor immune microenvironment	Assessment of stromal CD8+ CTL density, plasma cells (CD138/MUM1), mature tertiary lymphoid structures (CD20/CD23), and CTL/Treg (FOXP3) ratio.	Mainly pre surgery (T2), compared with baseline biopsy collected at inclusion (T1).
Objective Response Rate (ORR)	Evaluate tumor response to neoadjuvant treatment.	From study inclusion until completion of the 3 planned neoadjuvant chemotherapy cycles, prior to surgery
Pathological Complete Response (pCR)	Assess the absence of viable tumor cells in the surgical specimen.	T2 (surgery)
Major Pathological Response (MPR)	Evaluate residual tumor burden following neoadjuvant therapy.	T2 (surgery).
Disease-Free Survival (DFS)	Evaluate recurrence-free survival following treatment.	T3 (6 weeks post-surgery) and T4 (3 months post-surgery).
Treatment-Related Toxicities	Incidence, nature, and severity of adverse events according to CTCAE v5.0.	During the first, second, and third cycles of neoadjuvant chemotherapy ( Each cycle is separated by 21 days).
Postoperative Complications	Incidence and severity of postoperative complications according to Clavien-Dindo classification.	T3 (6 weeks post-surgery).
Length of Postoperative Hospital Stay	Number of hospital days following surgery.	Assessed 6 weeks after surgery (T3)
90-Day Postoperative Mortality	Mortality occurring within 90 days after surgery.	T4 (3 months post-surgery).
Change in Aerobic Capacity	Measurement of submaximal oxygen consumption.	at study inclusion and at the pre-surgery visit.
Change in Peripheral Muscle Strength	Assessment of quadriceps isometric strength and core endurance (plank test).	at study inclusion and at the pre-surgery visit.
Change in Functional Capacity	Six-Minute Walk Test (6MWT) and handgrip strength.	at study inclusion and at the pre-surgery visit.
Change in Functionnal capacity	Handgrip test strength.	at study inclusion and at the pre-surgery visit.
Change in Lean and Fat Mass	Body composition analysis using (CT-scan) imaging at the L3 vertebral level and bioimpedance assessment	at study inclusion and at the pre-surgery visit.
Level of physical activity	International Physical Activity Questionnaire (IPAQ) score. The IPAQ assesses physical activity levels based on self-reported frequency and duration of physical activities. Higher scores indicate higher levels of physical activity.	at study inclusion and at the pre-surgery visit.
Change in Quality of Life	Evaluation using EORTC QLQ-F17	at study inclusion and at the pre-surgery visit.
Change of quality of life	Evaluation using EORTC QLQ-LC13 questionnaires.	at study inclusion and at the pre-surgery visit.
Change in Cancer-Related Fatigue	Assessment using the FACT-Fatigue questionnaire.	at study inclusion and at the pre-surgery visit.
Change in Circulating Immune and Inflammatory Biomarkers	Analysis of cytokines and myeloid/lymphoid cell populations using flow cytometry and MSD technology.	At study inclusion, during the second cycle of neoadjuvant chemotherapy(Each cycle is separated by 21 days) and before surgery
Participation Rate	Proportion of eligible patients enrolled in the study.	At screening and 6 months
Exercise Program Adherence	Exercise adherence measured as the percentage of prescribed exercise sessions completed. Values range from 0% to 100%, with higher percentages indicating greater adherence.	Assessed at study inclusion, during the first, second, and third cycles of neoadjuvant chemotherapy (each cycle is separated by 21 days), and at the pre-surgery visit
Attrition Rate	Proportion of participants withdrawing from the study.	6 months
Program Acceptability and Satisfaction	Participant satisfaction with the exercise intervention, assessed using a self-administered questionnaire developed specifically for this study	pre-surgery (T2) : intervention arm only

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ancillary - Characterize Exercise-Induced Changes in the Tumor Immune Microenvironment	To identify immune signatures, molecular pathways (immune response, angiogenesis, metabolism), and cellular populations modulated by exercise through RNA sequencing and high-dimensional spatial imaging (Akoya Phenocycler™).	Comparison of tumor samples collected at baseline from the pre-treatment biopsy and at surgery

Collaborators and Investigators

• Sponsor: Centre Leon Berard

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 10, 2026
• First Submitted That Met QC Criteria: August 25, 2026
• First Posted (Actual): August 26, 2026

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: physical Activity
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Behavior; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Exercise; Methods
• Other Study ID Numbers: ERICA-02 (ET26-082)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No