Neoplasms

All Conditions

Symptoms and General Pathology

Adenocarcinoma

Neoplasm Metastasis

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Vitamins

Leucovorin

Fluorouracil

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Immunomodulating Agents

Folic Acid

Folfirinox

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

FOLFIRI (IV; folinic acid 400 mg/m\^2, irinotecan 180 mg/m\^2, 5-FU bolus 400 mg/m\^2 and continuous infusion 2,400 mg/m\^2/46h (dose adjustment will be accepted).

OSE2101 - subcutaneous injection on day 1 and day 15, every 4 weeks for 6 doses then every 8 weeks until month 12 then every 12 weeks up to 24 months.

FOLFIRI - schedules as in Arm A until disease progression on unacceptable toxicity

Intravenous (IV); folinic acid 400 mg/m\^2, irinotecan 180 mg/m\^2, 5-FU bolus 400 mg/m\^2 and continuous infusion 2,400 mg/m\^2

FOLFIRI

subcutaneous injection on days 1 and 15, every 4 weeks for 6 doses then every 8 weeks until month 12 and then every 12 weeks for a maximum treatment duration of 24 months

OSE2101

Cindy NEUZILLET, MD

Marie-Line GARCIA LARNICOL, MD

Khadija KALAI, MD

Vincent HAUTEFEUILLE, MD

Hocine FAYCAL, MD

Christophe BORG, MD

Nathalie BONICHON LAMICHHANE, MD

Jean Philippe METGES, MD

Elisabeth CAROLA, MD

Isabelle BAUMGAERTNER, MD

François GHIRINGHELLI, MD

Antoine DROUILLARD, MD

Anthony TURPIN, MD

Christelle de LA FOUCHARDIERE, MD

Julien FORESTIER, MD

Marielle GUILLET, MD

Marion CHAUVENET, MD

Jérôme DESRAME, MD

Jérome DESRAME, MD

Yves RINALDI, MD

Marine GILABERT, MD

Jean Baptiste BACHET, MD

Isabelle TROUILLOUD, MD

Christophe LOUVET, MD

David TOUGERON, MD

Olivier BOUCHE, MD

Meher Ben Abdelghani, MD

Alain GRATET, MD

Thierry LECOMTE, MD

Aurélien LAMBERT, MD

TEDOPAM is a randomized (1.1.1) non-comparative phase II study. This study will assess the efficacy and safety of OSE2101 alone or in combination with nivolumab followed by FOLFIRI reintroduction, versus FOLFIRI as maintenance therapy in patients with advanced PDAC after induction therapy with FOLFIRINOX.

Current standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC) is chemotherapy, preferential regimen being FOLFIRINOX (5FU, leucovorin, irinotecan, and oxaliplatin) in fit patients (PS 0-1, bilirubin \< 1.5 ULN). The question of how and when the FOLFIRINOX regimen and doses can be deescalated after a period of disease control (i.e. maintenance therapy) remains unanswered. In routine practice, oxaliplatin is usually stopped after 6-8 cycles due to limiting neuropathy, and the fluoropyrimidine is continued, either alone or, more frequently, in combination with irinotecan (FOLFIRI regimen), until disease progression.

Immune therapies have opened new opportunities in cancer therapy. However, results of immunotherapy in PDAC have been disappointing so far, with failure of checkpoint inhibitor monotherapies (anti-CTLA4 and anti-PD-L1 monoclonal antibodies \[mAb\]) in progressive advanced PDAC, while monovalent vaccines were demonstrated to be safe but with limited activity.

Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma

A Randomized Non-comparative Phase II Study of Maintenance Therapy With OSE2101 Plus FOLFIRI, or FOLFIRI After Induction Therapy With FOLFIRINOX in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (TEDOPaM-D17-01 PRODIGE 63 Study)

The OS is defined according to the DATECAN (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment

The PFS is defined according to the DATECAN consensus as the time from randomization to first progression or death for any reason, whichever occurs first. In the absence of event (confirmation of progression or death), PFS status will be censored at the date of the last radiological assessment.

PFS according to RECIST (Response Evaluation Criteria In Solid Tumors) v1.1 in the FOLFIRI arm (Arm A) and iRECIST (immune Response Evaluation Criteria In Solid Tumors) in the immune therapy arms (Arm B and C) by centralized review of CT-scan imaging

The SSR is derived from the duration of disease control (DDC), which is defined as the PFS, or, if FOLFIRI is reintroduced and achieves partial response (PR) or stable disease (SD), as the addition of the initial PFS (PFS1) and the PFS of the reintroduction PFS (PFS2)

All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Response according to RECIST v1.1 in the FOLFIRI arm (Arm A) and iRECIST in the immune therapy arms (Arms B and C) (centralized review of CT-scan imaging); a comparative analysis of tumor response according to these two evaluation rules will be performed in Arm B and C

Rate of patients with an improvement of their quality of life score according to EORTC QLQ-C30. A quality of life score is obtained according to the answers to the 30 questions. The Minimal Clinically Important Difference (MCID) will be fixed to 10 points.

Q-TWiST analysis considers three health states, TOX (toxicity), TWiST, and REL (The duration of the relapse), and the duration of each state is calculated for every patient.

The TOX state comprises the total number of days after randomisation and before strategy failure spent with toxicity, regardless of when the toxicity started or whether there were gaps between toxicities. All grade 3 or 4 toxicities attributable to the study drugs are included in the analysis, apart from those starting after strategy failure.

The TWiST state is defined as DDC time minus time with toxicities.

The duration of the relapse or REL state is defined as OS time minus DDC time, or the period of time from progression to death. Patients alive at the end of the study are censored for the OS endpoint.

OSE Immunotherapeutics

GERCOR - Multidisciplinary Oncology Cooperative Group

Respiratory Tract (Lung and Bronchial) Diseases

Behaviors and Mental Disorders

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Disease Progression

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Quality of Life

Vaccines

Immune Checkpoint Inhibitors

Pemetrexed

Docetaxel

Tubulin Modulators

Antimitotic Agents

Folic Acid Antagonists

OSE2101 was administered as a 1 mL-subcutaneous injection on Day 1 every three weeks for six cycles, then every eight weeks for the remainder of year one and finally every twelve weeks beyond year one until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal. Should pseudo progression or delayed response to treatment suspected in arm A, investigator may continue treatment beyond the time of RECIST-defined progression, if the patient is perceived to be experiencing clinical benefit of OSE2101. OSE2101 dose was 5 mg of peptides (0.5 mg for each peptide).

Patients receiving docetaxel: Docetaxel 75 mg/m2 will be administered by intravenous infusion over 1 hour on Day 1 of a 21-day cycle.

Patients receiving pemetrexed: Pemetrexed, 500 mg/m2, will be administered by intravenous infusion over 10 minutes on Day 1 of a 21-day cycle.

Docetaxel and pemetrexed will be continued until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal.

Dominique Costantini, Dr

The aim of this clinical trial was to determine if the therapeutic cancer vaccine OSE2101 (TEDOPI) was more effective than standard chemotherapy (docetaxel or pemetrexed) in treating HLA-A2 positive patients with metastatic NSCLC who progressed after sequential or concurrent chemotherapy and immune checkpoint inhibitor given in first or second-line treatment.

The main questions were to compare the survival, the tolerance to treatment and the quality of life of patients between the two arms of treatment (OSE2101 versus standard chemotherapy)

The study was a two-step randomized (2:1) study. Patients were stratified by histology (non-squamous versus squamous), best response to first-line treatment \[complete response or partial response versus stable disease or progressive disease\] and line of treatment with prior ICI (first-line ICI when combined with platinum-based chemotherapy versus second-line ICI when administered as sequential treatment). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of the interim analysis, a decision was taken to early stop the accrual due to COVID-19 after 219 out of 363 patients were randomized. It led to a decrease of the study power from 80% to 62%. At the time of the interim analysis, a subgroup of patients was identified from stratification factor based on a clinical and biological rationale: those who received ICI second line and having received at least 12 weeks ICI. This subgroup was defined as ICI secondary resistance. The final analysis was carried out in the subgroup of patients with ICI secondary resistance and in all patients (ICI primary and secondary resistance).

Two-step open-label study with a planned interim OS futility in experimental arm per Fleming design (Step1) Central randomisation (2:1) with stratification by histology (non-squamous versus squamous), best response to first-line treatment \[complete response (CR) or partial response (PR) versus stable disease (SD) or PD\] and line of prior anti-PD(L)1 treatment (first-line when combined with platinum-based chemotherapy versus second-line when administered as sequential treatment after first-line platinum-based chemotherapy).

OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure

A Randomized Phase III Trial of OSE2101 Compared With Chemotherapy (Docetaxel or Pemetrexed) in HLA-A2 Positive Patients With Advanced Non-Small Cell Lung Cancer With Progressive Disease After Immune Checkpoint Inhibitors

The supporting information as Study Protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR) may be shared with other researchers if OSE Immunotherapeutics agreed and after signature of a confidential agreement between the parties

Objective Response rate (OOR) was defined as number of patients with Complete Response (CR) + Partial Response (PR) assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions. Investigator-assessed ORR was an exploratory endpoint as not relevant as primary, nor secondary endpoints to evaluate a cancer vaccine.

Duration of Objective Response (OOR) was defined as number of patients with Complete Response (CR) or Partial Response (PR) at 6 months assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions

Time to next lung cancer therapy was defined as the time from randomisation to the date of initiation of the first lung cancer therapy during the survival follow-up form

OS defined as the time from randomisation to death from any cause in patients with ICI secondary resistance

Post-progression survival was defined as the time from the earliest date of progression according to RECIST 1.1 until death in patients with ICI secondary resistance

Time to Worsening ECOG PS was defined as the time from randomization to the earliest date when ECOG PS was \>1 in patients with ICI secondary resistance. Time to worsening ECPG PS was summarized by treatment arm using the Kaplan-Meier method. The median event time for each treatment arm and the corresponding 2-sided 95% confidence interval were provided. By protocol, ECOG PS was not collected when a patient permanenetly discontinued the study treatment. Patients without ECOG PS worsening were censored at the last time when an ECOG value was recorded.

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following functional subscales analyzed separately: global health status, physical, role, cognitive, emotional and social functioning. Each score range from 0 to 100 after normalisation. Highest scores correspond to a better quality of life. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following symptoms subscales analyzed separately: Fatigue, Constipation, Dyspnea, Nausea and Vomiting, Pain, Insomnia, Appetite loss, Diarrhea, Financial Difficulties. Each score range from 0 to 100 after normalisation. Lowest scores correspond to a better QoL. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL.

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following symptoms subscales analyzed separately: Alopecia, Peripheral Neuropathy, Sore mouth, Dysphagia, Dyspnea, Pain in arm or shoulder, Pain in chest, Pain in other parts, Hemoptysis, Coughing. Each score range from 0 to 100 after normalisation. Lowest scores correspond to a better QoL. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL.

DCR at 6 months defined as the number of patients with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD) defined as neither sufficient shrinkage (compared to baseline) to qualify for CR or PR nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD) (e.g. decrease of the sum of the longest diameters of target lesions \<30% or increase up to 20%)

PFS was defined as the time from randomization to the earliest date of progression assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Progressive disease (PD) defined as increase of target lesions \>=20% taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest)

A total of 7 patients did not receive the study treatment (n=1 in OSE2101 arm, n=6 in docetaxel or pemetrexed arm).

Subcutaneous injection at 5 mg, 1 ml every 3 weeks for 6 cycles, then every 8 weeks until 1 year of treatment and thereafter every 12 weeks

Docetaxel by intravenous infusion over 1 hour at 75 mg/m2 every 3 weeks Pemetrexed by intravenous infusion over 10 minutes at 500 mg/m2 every 3 weeks both with premedication according to international guidelines

Docetaxel or Pemetrexed

Total

All randomized patients with ICI primary and secondary resistance

Primary efficacy analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI). Safety analysis was done in all patients.

Age, Categorical

Final analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI)

Age, Continuous

All patients with ICI primary and secondary resistance

Primary efficacy analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI)/ Safety analysis was done in all patients

Sex: Female, Male

Missing data in 11 patients (n=9 in OSE2101 arm, n=2 in docetaxel or pemetrexed arm)

Race/Ethnicity, Customized

United States

Czechia

Poland

Italy

Israel

France

Germany

Spain

Hungary

Region of Enrollment

219 HLA-A2 positive patients with advanced NSCLC who progressed after sequential or concurrent chemotherapy and Immune Checkpoint Inhibitor (either primary or secondary resistance) were randomized. Safety analysis was done in overall population. Primary efficacy analysis was carried out from stratification factor in subgroup of patients with ICI secondary resistance (who had a disease progression after ICI second line \> or equal to 12 weeks)

In April 2020 at time of planned interim analysis, decision was taken to prematurely stop the accrual due to COVID-19. Early termination led to small numbers of subject analyzed. The statistical plan was revised to propose the primary efficacy analysis in subgroup of patients with ICI secondary resistance (defined as progression after ICI second line \>= to 12 weeks from stratification criteria based on biological and clinical rationale).

Chief Medical Officer Immuno-Oncology

OS in the ITT population with ICI resistance (primary and secondary resistance)

OS analysis in patients with ICI secondary resistance defined as disease progression after ICI second line \> or equal to 12 weeks (n=118) OS analysis in the ITT population with ICI resistance (primary and secondary resistance) is described in statistical analysis 2 (n=219)

Overall Survival (OS)

Post-progression survival in patients with ICI secondary resistance

Post-progression survival in ITT population with ICI resistance (primary and secondary)

Patients with ICI secondary resistance defined as disease progression after ICI second line \> or equal to 12 weeks (n=118)

Post-Progression Survival

Time to worsening ECOG PS \>1 in patients with ICI secondary resistance

Time to worsening ECOG PS in the ITT population with ICI resistance (primary and secondary)

Time to Worsening ECOG PS

QLQ C30 Global Health Status in Patients with ICI secondary resistance

QLQ-C30 Physical functioning in patients with ICI secondary resistance

QLQ-C30 Role functioning in patients with ICI secondary resistance

QLQ-C30 Emotional functioning in patients with ICI secondary resistance

QLQ-C30 Cognitive functioning in patients with ICI secondary resistance

Global Health Status

Physical functioning

Role functioning

Emotional functioning

Cognitive functioning

Social funtioning

Mean Changes in Functional Subscales of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

QLQ-C30 Fatigue in ICI secondary resistance

QLQ-C30 Constipation in ICI secondary resistance

QLQ-C30 Dyspnea in ICI secondary resistance

QLQ-C30 Nausea and Vomiting in ICI secondary resistance

QLQ-C30 Insomnia in ICI secondary resistance

QLQ-C30 Appetite loss in ICI secondary resistance

QLQ-C30 Diarrhea in ICI secondary resistance

QLQ-C30 Financial difficulties in ICI secondary resistance

Fatigue

Constipation

Dyspnea

Nausea and Vomiting

Pain

Insomnia

Appetite loss

Diarrhea

Financial difficulties

QLQ-C30 Symptoms score changes from baseline in patients with ICI secondary resistance

Mean Changes in Symptoms Subscales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

QLQ-LC13 Alopecia in ICI secondary resistance

QLQ-LC 13 Peripheral neuropathy in ICI secondary resistance

QLQ-LC13 Sore mouth in ICI secondary resistance

QLQ-LC13 Dysphagia in ICI secondary resistance

QLQ-LC13 Pain in chest in ICI secondary resistance

QLQ-LC 13 Hemoptysis in ICI secondary resistance

QLQ-LC13 Coughing in ICI secondary resistance

Alopecia

Peripheral neuropathy

Sore mouth

Dysphagia

Pain in arm or shoulder

QLQ-LC 13 symptoms score changes from baseline in patients with ICI secondary resistance

Mean Changes in Symptoms Subscales of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Lung Cancer (QLQ-LC13) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma	NCT03806309	Pancreatic Duct... Locally Advance... Metastatic Canc...	FOLFIRI OSE2101	18 Years -	GERCOR - Multidisciplinary Oncology Cooperative Group
OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure	NCT02654587	Non Small Cell ...	OSE2101 Docetaxel Pemetrexed	18 Years -	OSE Immunotherapeutics

Spots Global Cancer Trial Database for ose2101

Every month we try and update this database with for ose2101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ose2101

Every month we try and update this database with for ose2101 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ose2101 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.