A patient who has not received any study drug(s) for > 6 weeks (e.g. equivalent to 2 cycles of 21 days) since last study drug administration should be discontinued from study treatment . 6 STATISTICAL METHODOLOGY AND ANALYSES 6.1 Statistical Analysis Plan A statistical analysis plan (SAP) will be written and finalized before the database lock . The SAP will provide full details of analyses, data displays and algorithms to be used for data derivations. The SAP will include the definition of major and minor protocol deviations and the link of major protocol deviations to the analys is sets. Major and minor protocol deviations will be identified before the study closure. The final SAP v2.2 was finalized on 23-july-2021 before the database lock . This SAP also details the subgroup analyses and variables used to define subgroups , and precisely describes the hierarchical order to test secondary endpoints . 6.2 Analysis Sets Three different analysis sets are defined for the patients with previous treatmen t with ICI . The primary population will be a Population of Interest (PoI) identified during Step -1 analysis consisting of patients from the 2d line ICI stratification factor with secondary resistance to ICI (i.e. duration of ICI ≥ 12 weeks) having shown a benefit over SoC and being proposed as the main population for final analysis . Sensitivity analyses on primary endpoint (OS) will be done in all population (Kluger et al., 2020) . Subjects not having a valid or substituted post -baseline value for a particular endpoint are excluded from the relevant analysis sets. ➢ Safety set This analysis set includes all patients who were randomized and received at least one dose of study treatment. Patients will be analyzed in the group according to the treatment they actually received. All safety data analyses will be analyzed using the safety set. ➢ Intent -to-Treat (ITT) set This ana lysis set includes all randomized patients. Patients will be analyzed in the group as randomized. All efficacy data analyses will be analyzed using the ITT set. ➢ Modified Intent -to-Treat ( mITT) set for testing the null hypothesis of the one stage Fleming Phase II design (at end of Step 1) For testing the null hypothesis of the one stage Fleming Phase II design at the end of Step 1 (Phase II part), this analysis set includes all patients of the ITT set, enrolled up to the end of Step 1, who received at least one dose of OSE2101 and are evaluable at 12 months after OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 69 of 101 02 February 2022 randomi zation, “evaluable ” meaning either known alive for at least 12 months or hav ing experienced death within 12 months . Patients will be analyzed in the group according to the treatment they actually received. ➢ Per-protocol set This analysis set includes all patients of the ITT set who did not violate the protocol in a way that might affect the evaluation of the effect of the study drugs on the main endpoints, i.e., without major protocol deviations. Major protocol deviations will be defined in the SAP. Selected sensitivity efficacy data analyses will be performed using the per -protocol set. ➢ Per protocol set for testing the null hypothesis of the one stage Fleming Phase II design (at end of Step 1) This analysis set includes all patients of the mITT set (for testing the null hypothesis of the one stage Fleming Phase II design ) who have no major protocol deviations and comply with the revised inclusion criterion #5 . Major protocol deviations will be defined in the SAP. Selected sensitivity efficacy data analyses will be performed using the per -protocol set . Nota bene: In addition, patients without previous treatment with ICI (included before recruitment hold) will be described separately. 6.3 Sample size Step 1 - Phase II The primary objective of Step 1 is to evaluate the overall survival rate after 12 months in OSE2101 arm. The following hypotheses are considered : - H0 (null): 25% of overall survival rate at 12 months (uninteresting to pursue any further investigation) - H1 (alternative): 40% of overall survival rate at 12 months (clinically relevant to discuss the interest of further investigation in a Phase III comparative trial ). According to the previous hypo theses and a Fleming one step Phase II design with a 2.5% one - sided type I error and a power of 80%, 84 evaluable patients have to be enrolled in the arm A. Fleming decision rules : Amongst the first 84 evaluable patients: To reject H0 we have to observe a t least 30 (35.7%) patients alive at 12 months , then it will be interesting to run the next step of Phase III comparative trial . If less than 30 patients are alive at 12 months, H0 will not be rejected and it will be considered uninteresting to pursue any further investigation . The probability to conclude for inefficacy whereas the true rate is 40% is β=18.1%. The probability to conclude for efficacy whereas the true rate is 25% is α=1.9%. In order to limit the total number of patient s needed in Step 1, a 2:1 randomization ratio to receive OSE2101 (Arm A) or pemetrexed or docetaxel (Arm B) will be used for new patients recruited when version 4.0 of the protocol comes into effect. A total of 38 patients with previous ICI treatment have been recruited before protocol version 4.0 , from whom 18 patients OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 70 of 101 02 February 2022 randomized in arm A (OSE2101), thus 84 - 18 = 66 new patients need to be recruited in arm A (OSE2101) . Based on a 2:1 randomization ratio, 6 6/2 = 3 3 new patients need to be randomized in arm B, leading to a total of 99 new evaluable patients. With an expected 7% rate of patients not evaluable at 12 months or withdrawn, a total of 108 new patients will be randomized for Step 1. The analysis of the Phase II data will take place once 84 subjects of the OSE2101 arm are evaluable for survival at 12 months (meaning that death was observed within 12 months or that the patient has a follow -up time of 12 months or more). With this sample size, the lower limit of the exact binomial two -sided 95% confidence interval will be above 25% as soon as at least 30 subjects will be alive at 12 months. In the situation where exactly 30 subjects out of 84 would be seen alive at 12 months, the observed survival rate at 12 months would be 35.7%, which seems reasonable in light of the 34.1% overall survival rate at 12 months published for 78 patients on durvalumab plus tremelimuab after failure to previous ICI (27). It may be noted that as soon as 55 deaths within 12 months are observed by the IDMC, there is no need to wait for 84 evaluable patients at 12 months since there is no possibility left to reach 30 or more patients alive at 12 months amo ng 84 patients evaluable at 12 months. Conversely as soon as 30 patients or more are observed alive at 12 months by the IDMC in patients evaluable at 12 months, there is no need to wait for 84 patients evaluable at 12 months since the number of patients al ive at 12 months cannot decrease with the additional observations (and since the lower limit of the 95% confidence interval is already above 25%). Step 2 - Phase III For Step 2, the same 2:1 randomization ratio will be continued . All the 38 patients rando mized before the rec ruitment hold in the subgroup of patients with p revious ICI treatment and all new patients included in Step 1 / Phase II will be followed during Step 2 /Phase III . However , the final analysis of Phase II /Phase III will exclude the 38 patients with previous ICI treatment randomized before protocol version 4.0. In order to reach a power of 80% for the two -sided log rank test at the 5% significance level when assuming a median OS of 7 months for the control and 10 mont hs for the experimental arm, a total of 278 events is required. If the new patients (randomized since version 4.0 of the protocol came into effect) are uniformly included over an accrual period of 36 months followed by a follow -up of 6 months after the las t inclusion , observing 278 events require s a total of 363 new patients . The actual number of new patients may be reduced if the 278 events are observed earlier (this is an event -driven study). Both counts exclude the 38 patients enrolled before protocol 4. 0. Step-1 analysis was reviewed by the independent data monitoring committee (IDMC) in March 2020. Step -1 data show ed that the predefined thresholds of 12 months -OS rate in OSE2101 arm was achieved. At this time, the IDMC was concerned about the impact of the COVID -19 pandemic on the primary endpoint of the study (OS), on the risk on data integrity and recommended to stop accrual early . OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 71 of 101 02 February 2022 The Sponsor decided to stop the accrual in April 2020. At that date, 219 patients have been enrolled instead of 363 patie nts and planned to be followed for survival up to mid -January 2021 . From Step -1 analysis, a population of interest (PoI) consisting of patients from the 2d line ICI stratification factor with secondary resistance to ICI (duration of ICI ≥ 12 weeks) was identified as having a benefit over SoC and being proposed as the main population for final analysis (Kluger et al., 2020) . Due to early study discontinuation due to COVID -19 (219 patients included instead of 363 patients), the power decreased to 62% with the same hypotheses (HR=0.70). Considering Step 1 results in the PoI , the following hypotheses have been proposed for final analysis : Assuming a HR of 0.55 observed in PoI in Step-1 and a median OS of 7 months in SoC (unchanged as initially planned), a total of 90 events in the PoI will provide a power of 80% and a 2-sided l ogrank test at a 5% two -sided level, if the patients are included over an accrual period of 48 months followed by a follow -up of 6 months after the last inclusion . 6.4 Primary and secondary efficacy endpoints The primary endpoint is OS, defined as time from r andomization to death, will be summarized on the ITT set using the Kaplan -Meier method and displayed graphically. The median event time for each treatment arm and the corresponding 2 -sided 95% confidence interval (CI) will be provided. A 2 -sided log -rank test stratified for the same stratification factors as used for the randomization will be used to compare OS between the two treatment arms. The Cox regression model, stratified for the same stratification factors, will be fitted, and the estimated hazard ratio and 2 -sided 95% CI will be provided. 2-sided unstratified log -rank test and an unstratified Cox regression model will also be used as secondary analyses for OS. Subgroups analyses of OS will be performed to determine whether treatment effect is consi stent among subgroups. The hazard ratios (obtained via a separate unstratified Cox model within each subgroup) and their 95% confidence intervals will be displayed as a forest -plot, the test of interaction between treatment and subgroup will be derived fro m an unstratified Cox model applied on the whole study population. The following variables will be used to define subgroups: • histology (squamous vs. non-squamous), • initial response to first line treatment (objective response, that is either complete or partial response, vs. no objective response, that is either stabilization or progressive disease) • line rank of ICI therapy (2nd line vs. 1st line). • best response to ICI (objective response, vs no objective response ) • presence vs absence of brain metastases • tumor stage (III vs. IV) • previous number of systemic treatment lines (1 vs. 2 or more) • gender (male vs female) • age (< 75 vs. ≥ 75) • Smoking status: never, former or current smoker • baseline ECOG score (0 vs. 1) OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 72 of 101 02 February 2022 • duration of PFS since previous treatment ( shorter or longer than 6 months ) Additionally, a Cox regression model, stratified for the same stratification factors as used for the randomization, will be used to explore the potential influences of the other factors (those defining subgroups in the text above) on the primary OS endpoint. The full list of subgroups of interest will finalized before database lock and detailed in the SAP . The 6 -months survival probability will be estimated using the Kaplan -Meier method and a 2 - sided 95% CI for the log [ -log(6 -months survival probability)] will be calculated using a normal approximation and then back transformed to give a confidence interv al for the 6 -months survival probability itself. The 1 -year survival probability will be estimated similarly. Once the primary objective will be established (significant result on OS), each of the secondary efficacy endpoints will be tested at 5% significance level using a further hierarchical order ( OS (PP), PPS, Time to worsening of ECOG PS , QLQ-C30 Global health status score change from baseline , QLQ -C30 Functional scores change from baseline , QLQ -C30 Symptom scores change from baseline , QLQ -LC13 Symptom scores change from baseline , DCR at 6 months , DCR at 12 months , , followed by PFS) in order to control the overall type I error. If the primary objective is not established, these endpoints will still be analyzed but interpreted as exploratory en dpoints, similarly if one secondary endpoint in the sequence is not significant, the lower rank secondary endpoint(s) will be considered exploratory. Based on the randomized patients with measurable lesions at baseline, the best response (CR, PR, SD or PD) will be determined by radiology review for each patient and will be summarized by treatment arm. Assessment of response will be made using RECIST version 1.1 (Appendix 1). Then DCR at 6 and 12 months will be calculated as the number of patients remaining within CR, PR or SD responses within the considered time period divided by the total number of randomized patients with measurable lesions at baseline in each treatment group. DCR will be analyzed as described for ORR. The corresponding exact 2 -sided 95% confidence interval will be calculated. The Mantel Haenszel test will be used to compare DCR at 6 months between the treatment arms, using the randomization strata, the corresponding odds -ratio will be provided with its 95% confidence interval. In additio n, the difference in DCR at 6 months between the two treatments will be provided and its 95% confidence interval will be calculated based on the normal approximation. The secondary efficacy endpoints associated with HRQoL will be the change from baseline i n the EORTC QLQ -C30 “Global health status/QoL” score (based on questions 29 and 30) , for EORTC QLQ -C30 functional scores , and for EORTC QLQ -C30 and QLQ -C13 symptoms according to repeated measures mixed -effects modeling . The composite endpoint time to 1st ≥ 10-point deterioration in EORTC QLQ -LC13 “Chest pain symptom ” score (based on question 40) , “Dyspnea symptom ” score (based on questions 33, 34, 35) or “Cough ing symptom ” score (based on question 31) , whichever happens first . Scores will OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 73 of 101 02 February 2022 be derived from the EORTC QLQ -C30 and EORTC QLQ -LC13 questionnaires items according to the respective scoring manuals . PFS, defined as time from randomization to the first documented disea se progression or death whichever occurs first, will be analyzed similarly as described for OS. A log -rank test, stratified by the same stratification factors as used for the randomization, will be used in analyzing PFS. PPS, defined as time from the first documented disease progression in patients having experienced a progression to death , will be analyzed similarly as described for OS . Time to worsening of ECOG PS, defined as the time from randomization to the earliest time when the ECOG becomes greater than 1 ignoring all assessments performed after the analysis cut-off date. Patients who die without having recorded an ECOG >1 will be assigned an ECOG = 5 (Dead) at the time of death. Patients without worsening ECOG will be censored at the last time when an ECOG value was recorded. By protocol, ECOG is not collected anymore when a subject discontinues study treatment while the time between study treatment discontinuat ion and death can be quite long , an additional analysis without imputation for death will be performed. This analysis will exclude patients without any post -baseline ECOG assessment and censor patients without observed ECOG worsening at their last ECOG ass essment . The endpoint will be analyzed as described for the PFS . 6.5 Exploratory efficacy endpoints ORR will be calculated as the number of patients with a best response of CR or PR divided by the total number of randomized patients with measurable lesions at baseline in each treatment group. ORR will be analyzed as described for DCR at 6 months . DR will be calculated for the subgroup of patients with objective disease response and summarized using the Kaplan -Meier method. The 3 endpoints TTD in patient report ed pain (QLQ -LC13 “Chest pain symptom ” score), TTD in patient reported dyspnea (QLQ -LC13 “Dyspnea symptom ” score), and TTD to patient reported cough (QLQ -LC13 “Coughing symptom ” score), will be defined as the time from randomization to the earliest time th e patient’s score shows a 10 -point or higher increase after baseline ( 7, 6). Patients will be censored at the last time when they completed an assessment for chest pain, dyspnea and cough if they have not deteriorated. A 10 point or higher change in the score is perceived by patients as clinically significant ( 58). TTD of each these 3 pre-specified symptoms (chest pain, dyspnea, and cough) scales will be summar ized using Kaplan -Meier methods. The estimated Kaplan -Meier plots will be provided for each symptom and the unstratified log -rank test will be the primary method to compare the time to first deterioration between the two treatment groups. The median time a nd the corresponding 2 -sided 95% CI also will be provided. The Hochberg procedure will be used to adjust for multiplicity of the three pre -specified symptoms. OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 74 of 101 02 February 2022 Patient reported HRQoL will also be assessed in a detailed manner in the SAP . Summary statistics (mean [and SE], median, range and 95% CI) will be reported by treatment arm and visit for the items and scales of the EORTC QLQ -C30 and QLQ -LC13 questionnaires . The mean change from baseline (and 95% CI) will also be reported . Line charts depicting the means and mean changes of subscales over time will be provided for each treatment arm. The number and proportion of patients who improved, worsened, or remained stable for each of the symptom and functional domains, global QOL, and single items of the EORTC QLQ -C30 and QLQ -LC-13 questionnaires will be summarized in a table and compared between the two treatment arms. Additional analyses may be performed such as repeated measures mixed -effects modeling. Time to next lung cancer th erapy, defined as time from randomization to the first recording a lung cancer therapy , will be analyzed similarly as described for OS. A log -rank test, stratified by the same stratification factors as used for the randomization, will be used. COVID -19 Impact : it is proposed to test COVID -19 impact in the ITT population following FDA Guidance (Updated January 27, 2021 then August 2021 on “Conduct of Clinical Trials of Medical Products During COVID -19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards. ” and “ Statistical Considerations for Clinical Trials During the COVID -19 Public Health Emergency: Guidance for Industry ” June 2020 . The complete description of COVID -19 impact analyses is described in the SAP . 6.6 Safety and tolerability endpoints All AEs and SAEs will be coded using the MedDRA dictionary. All AEs will be tabulated by system organ class (SOC), preferred terms (PT) and low -level terms (LLT) within each SOC. The incidence of subjects who experienced AEs coded with the same preferred term will be tabulated (in descending order according to the incidence in the investigational study drug group). Adverse events will also be tabulated by severity and by relationship to study drug. Summary tab les will be accompanied by individual subject listings. AEs corresponding to hypersensitivity reactions will be considered as adverse events of special interest and will be detailed in additional summary tables. SAEs occurring after study drug initiation will be listed and summarized similarly to AEs, while SAEs occurring before study drug initiation (only those related to study - mandated procedures) will be listed only. The same analyses will also be conducted on the irAEs. Vital signs (blood pressure and pulse rate) and ECG will be summarized by descriptive statistics by treatment group. Individual subject listings of vital signs and ECG data will be provided. Values for safety laboratory parameters will be summarized by descriptive statistics by treatme nt group . Individual subject listings will be provided. 6.7 Interim analysis No interim analysis of the primary endpoint will be performed. However, OS rate at 12 months will be analyzed on Arm A at end of Step 1 by the IDMC , before a decision to continue Step 2 can be made by the Steering Committee after recommendation by OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 75 of 101 02 February 2022 the IDMC . The decision of moving forward in Step 2 (Phase III ) will consider the expected benefit of OSE2101 as well the relevance of the specific design of the Phase III with regards to the state -of-the-art in the management of advanced NSCLC known at time of the analysis. 6.8 Exposure to study drugs Exposure to study drugs will be described in terms of administered doses. The exposure will be tabulated using th e usual location and scale statistics. 6.9 Baseline Parameters and Concomitant Medications Continuous demographic variables (age, height, weight) will be summarized by descriptive statistics (mean, median, SD, minimum, maximum and number of available observa tions). Individual subject listings will be provided. Qualitative demographic characteristics (gender) will be summarized by counts and percentages. Other subject characteristics (medical history, physical examination findings, previous and concomitant med ications) will only be listed. Previous and concomitant medications will be coded according to the WHO drug code and the ATC code. They will be summarized by type (i.e., previous and concomitant) by tabulating the number and percentages of subjects having received each medication. 7 PROCEDURES AND QUALITY ASSURANCE 7.1 Procedures 7.1.1 Protocol amendments Any change to a protocol has to be considered as an amendment as soon as these documents have been submitted to Ethics Committee (ECs)/Institutional Review Board (IRB) and Health Authorities. Therefore, an amendment could occur before or after the approval of these documents by ECs/IRBs and Health Authorities . Potential amendments must be approved by the Sponsor after discussion within the Steering Committee, as appropriate. Changes in the core Subject Information sheet and Informed Consent form requested b y ECs/IRBs are not considered as amendments, as long as they do not significantly affect the protocol. ➢ Non-substantial amendment Administrative or logistical minor changes require a non -substantial amendment. Such changes include but are not limited to cha nges in study staff or contact details, change in laboratory normal ranges, or minor changes in the packaging of study drug, etc. The implementation of a non-substantial amendment could be done with or without (according to national regulations) notificat ion to the appropriate ECs/IRBs and Health Authorities. It does not require their approval or to be signed by the investigators. ➢ Substantial amendment OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 76 of 101 02 February 2022 Significant changes require a substantial amendment. They include but are not limited to: new data affec ting the safety of subjects/patients, change of the objectives/endpoints of the study, eligibility criteria, dose regimen, study assessments/procedures, treatment or study duration, with or without the need to modify the Subject Information and Informed Co nsent. Substantial amendments are to be approved by the appropriate ECs/IRBs and in some countries by the Health Authorities . The implementation of a substantial amendment can only occur after formal approval by the appropriate ECs/IRBs and/or Health Autho rities and must be signed by the investigators. ➢ Urgent amendment An urgent amendment might become necessary to preserve the safety of the subjects included in the study. The requirements for approval should in no way prevent any immediate action being taken by the Investigator or OSE Immunotherapeutics in the best interest of the subjects. Therefore, if deemed necessary, an investigator can implement an immediate change to the protocol for safety reasons. This means that, by exception, the implementation of urgent amendments will occur before submission to and approval by ECs/IRBs and Health Authorities. In such cases, the investigator must notify OSE Immunotherapeutics within 24 hours. A related substantial amendment will be written within 10 working days by OSE Immunotherapeutics and submitted to the appropriate ECs/IRBs and Health Authorities. 7.1.2 Monitoring The OSE Immunotherapeutics monitor(s) or its designee will contact and visit the investigator regularly and will be allowed, on request, to have access t o all source documents needed to verify the entries in the eCRF and other protocol - related documents; provided that subject confidentiality is maintained in agreement with local regulations. It will be the monitor's responsibility to inspect the eCRF at r egular intervals throughout the study, to verify the adherence to the protocol and the completeness, consistency and accuracy of the data being entered in them. OSE Immunotherapeutics monitoring standards require full verification for the presence of infor med consent, adherence to the inclusion/exclusion criteria, documentation of SAEs and the recording of the main safety and tolerability and efficacy endpoints. The investigator must ensure that subjects' anonymity will be maintained. On eCRFs or other documents submitted to OSE Immunotherapeutics, subjects should not be identified by their names, but by birth date (upon local regulation ) and number. The investigator must keep a subject/patient log showing the subject’s number, name, date of birth and addre ss or any other locally accepted identifiers. Documents identifying the subjects/patients (e.g., signed informed consent forms) must not be sent to OSE Immunotherapeutics and must be kept by the investigator in strict confidence. The investigator and co -investigators agree to cooperate with the monitor(s) to ensure that any issues detected in the course of monitoring visits are resolved. If the subject is hospitalized or dies in a hospital other than the study center, the investigator is in charge of contac ting this hospital in order to document this SAE. OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 77 of 101 02 February 2022 The investigator will supply OSE Immunotherapeutics or its designee on request with any required background data from the study documentation or clinic records. This is particularly important when errors in data transcription are suspected. In case of special problems and/or governmental queries, it is also necessary to have access to the complete study records, provided that patient confidentiality is protected. An initiation visit will be performed before the first subject is included. Monitoring visits and contacts will occur at regular intervals thereafter. A close -out visit will be performed after the database lock and resolution of all pending queries and follow -up of ongoing AEs/SAEs. 7.1.3 Data management 7.1.3.1 Data collection An eCRF must be completed and signed by the principal investigator or co -investigator only when a patient has been randomized. This also applies to those subjects who prematurely discontinue the study. If a subject withdraw s from the study, the reason must be noted on the eCRF. The eCRFs are to be completed on an ongoing basis. 7.1.3.2 Database management and quality control All study data will be entered into the study database, according to validated procedures described in specific data management documents. Subsequently, the data will be systematically checked using specific quality control procedures. When the database will be declared complete, clean and accurate, it will be locked. Any changes to the database after t hat time can only be made by joint written agreement between the Clinical Research Physician and the Trial Statistician. 7.1.4 Recording of data and retention of documents The investigator will maintain adequate and accurate records to enable the conduct of the study to be fully documented and the study data to be subsequently verified. These documents will be classified into two different categories: investigator's file, and subject clinical source documents. The investigator's file will contain the protocol/am endments, FDA form 1572 for studies conducted under an US IND, financial disclosure form, EC/IRBs and Health Authority approval with correspondence, informed consent forms, drug records, staff curriculum vitae and authorization forms, screening and enrollm ent logs, and other appropriate documents/correspondence as per ICH/GCP guidelines and local regulations. Electronic filing of eCRF must also occur. Subject clinical source documents include, but are not limited to subject hospital/clinic records, physicia n's and nurse's notes, appointment book, original laboratory reports, ECG, X -ray, pathology and special assessment reports, consultant letters, etc. These two categories of documents must be kept on file by the investigator for as long as needed to comply with national and international regulations (2 years after the last marketing OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 78 of 101 02 February 2022 authorization in an ICH/GCP region or following local requirements is it is a longer period). No study document should be destroyed without prior written approval from OSE Immun otherapeutics or its designee . Should the investigator wish to assign the study records to another party, or move them to another location, OSE Immunotherapeutics or its designee must be notified in advance. When source documents are required for the conti nued care of the patient, appropriate copies should be made for storing outside of the site. 7.1.5 Audit OSE Immunotherapeutics or its designee may conduct audits of clinical research activities in accordance with its internal Quality System to evaluate complia nce with the protocol and the principles of ICH/GCP related guidelines. Health Authorities may also wish to conduct an inspection (during the study or after its completion). Should an inspection be requested by Health Authorities, the investigator must inf orm OSE Immunotherapeutics or its designee immediately that such request has been made. The investigator will permit such audits by OSE Immunotherapeutics (and its designee) or Health Authorities and facilitate them by providing access to the relevant sour ce documents. 7.1.6 Publication of study results The clinical study report will be signed by the chair of the Steering Committee. In accordance with standard editorial and ethical practice, results of OSE Immunotherapeutics sponsored studies will be published. Authors will be defined as meeting requirements of the International Committee of Medical Journal Editors. The list of authors will consider for ranking Committee members, investigators according to the number of inclusions, region representatio n. Other contributions may be acknowledged. The data collected during this study are confidential and proprietary to the sponsor. Any publications or abstracts arising from this study require approval by the sponsor prior to publication or presentation and must adhere to the sponsor’s publication requirements as set forth in the approved clinical trial agreement (CTA). All draft publications, including abstracts or detailed summaries of any proposed presentations, must be submitted to the sponsor at the earliest practicable time for review, but at any event not less than 30 days before submission or presentation unless otherwise set forth in the CTA. Sponsor shall have the right to delete any confidential or proprietary information contained in any proposed presentation or abstract and may delay publication for up to 60 days for purposes of filing a patent application. 7.1.7 Disclosure and confidentiality By signing the protocol, the investigator agrees to keep all information provided by OSE Immunotherapeutics in strict confidence and to request similar confidentiality from his/her staff and the EC/IRB. Study documents provided by OSE Immunotherapeutics (Investigators' OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 79 of 101 02 February 2022 Brochure, protocol, CRF and any other protocol -related documents) will be stored appropriately to ensure their confidentiality. The information provided by OSE Immunotherapeutics to the investigator may not be disclosed to others without direct written authorization from OSE Immunotherapeutics, except to the extent necessary to obtain informed consen t from subjects who wish to participate in the trial. Furthermore, the investigator agrees that the sponsor is allowed to enter and utilize his/her professional contact details in an electronic database for internal purposes and for submission to worldwide Health Authorities. 7.1.8 Premature termination or suspension of the study Both OSE Immunotherapeutics and the investigator reserve the right to terminate the study at any time. If a study is prematurely terminated or suspended, OSE Immunotherapeutics will pr omptly inform the investigator, the ECs/IRBs and Health Authorities, as appropriate, and provide the reason(s) for the termination or suspension. If the study is prematurely terminated or suspended for any reason, the investigator in agreement with OSE Imm unotherapeutics should promptly inform the enrolled subjects and ensure their appropriate treatment and follow -up. In addition, if the investigator terminates or suspends a study without prior agreement of the sponsor, the investigator should promptly info rm OSE Immunotherapeutics and the EC/IRB, and should provide the sponsor and the EC/IRB with a detailed written explanation of the termination or suspension. If the EC/IRB terminates or suspends its approval/favorable opinion of a study, the investigator should promptly notify OSE Immunotherapeutics and provide OSE Immunotherapeutics with a detailed written explanation of the termination or suspension. 7.2 Insurance and Compensation to subjects and investigators The sponsor is providing insurance in order to i ndemnify (legal and financial coverage) the investigator/center against claims arising from the study, except for claims that arise from malpractice and/or negligence. The compensation of the subject in the event of study -related injuries will comply with the applicable regulations. OSE2101 Protocol OSE2101C301 Confidential Version n°6.0 Page 80 of 101 02 February 2022 8 REFERENCES 1.