Non Small Cell Lung CancerPhase 3ATALANTE-1NCT02654587
OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure
A Phase 3 study testing OSE2101, Docetaxel and Pemetrexed in people with Non Small Cell Lung Cancer, run by OSE Immunotherapeutics at 78 sites in 10 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- OSE2101, Docetaxel and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 219 participants
- Where
- 78 sitesin 10 countries
- Study dates
- 12 Feb 2016to 15 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated informed consent
- Willingness and ability to comply with the clinical study procedures.
- Female or male, 18 years of age or older
- Histologically or cytologically proven diagnosis of Non-Small Cell Lung Cancer (NSCLC) that is locally advanced (stage III) unsuitable for radiotherapy or metastatic (stage IV) according to the 8th edition of tumor, node, metastasis (TNM) in Lung Cancer
- Subjects with disease recurrence or progression after immune checkpoint inhibitor and platinum-based chemotherapy:
- either 1st line chemotherapy followed by 2nd line immune checkpoint inhibitor, or ii) 1st line combination of immune checkpoint inhibitor and chemotherapy Patients with progression during or within 12 months after the end of immune checkpoint inhibitor given as sequential or concomitant platinum-based chemotherapy ± radiation for locally advanced disease (stage III) were eligible
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- Subjects with measurable or non-measurable lesions according to RECIST 1.1
- Subjects must express HLA-A2 phenotype (central test in blood)
- Subjects must be considered suitable for chemotherapy with single-agent pemetrexed or single-agent docetaxel
- Subjects with brain metastases were eligible if treated (whole brain radiotherapy, stereotaxic radiotherapy, surgery) at least 3 weeks prior to initiation of study treatment and have no symptoms related to brain metastases for at least 2 weeks before initiation of study treatment and are not taking any forbidden medications
- Any prior chemotherapy, immunotherapy, hormonal therapy, radiation therapy or surgeries must have been completed at least 3 weeks prior to initiation of study treatment.
- Any toxicity from prior therapy must have recovered to ≤ Grade 1 (except alopecia)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate organ function as defined by all the following criteria:
- Albuminemia > 25g/L
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 1.5 x upper limit of normal (ULN) with alkaline phosphatase ≤ 2.5 x ULN, or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to liver metastases
- Total serum bilirubin ≤ 1.5 x ULN
- Absolute neutrophil count (ANC) ≥ 1500/L
- Platelets ≥ 100000/L
- Hemoglobin ≥ 9.0 g/dL (in the absence of transfusion within 2 weeks before randomization)
- Creatinine clearance (based on modified Cockcroft-Gault formula) ≥ 45 ml/min.
Who cannot join
- Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas)
- Patients with squamous cell carcinoma histology, and who had docetaxel as part of his prior chemotherapy
- Current or previous treatment with investigational therapy in another therapeutic clinical trial (interrupted less than 4 weeks before study treatment initiation)
- Patients whose tumor harbors EGFR gene mutation that sensitizes tumors to Tyrosine-Kinase Inhibitor (TKI) (EGFR exon 18-21) or Anaplastic Lymphoma Kinase (ALK) rearrangement
- Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)
- Spinal cord compression (unless treated with the patient attaining good pain control and stable or recovered neurologic function), carcinomatous meningitis, or leptomeningeal disease
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- Patients with squamous cell histology or non-squamous cell histology previously treated by pemetrexed with a contraindication for docetaxel with grade ≥ 2 neuropathy or hypersensitivity reaction to medications formulated with polysorbate 80 (Tween 80)
- Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
- Treatment with corticosteroids in the last 3-week period before inclusion, except for topical, ocular, intra-articular, intranasal, and inhaled corticosteroids with minimal systemic absorption (e.g. with a dose ≤ 500 microgram beclomethasone equivalent for inhaled steroids), or steroid doses ≤ 10 mg daily prednisone equivalent which are permitted
- A recognized immunodeficiency disease including human immunodeficiency virus (HIV) infection (and other cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary, congenital or acquired immunodeficiencies)
- Patients with auto-immune disease, with the exception of type I diabetes or treated hypothyroidism
- Patients with interstitial lung disease
- Patients with active B or C hepatitis
- Other malignancy: patients will not be eligible if they have evidence of other active invasive cancer(s) (other than NSCLC) within 5 years prior to screening (except appropriately treated non-melanoma skin cancer or localized cervical cancer, or other local tumors considered cured (e.g.localized and presumed cured prostate cancer)
- Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study
- Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment
- Male patients sexually active with a woman of childbearing potential must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator
- Breastfeeding women
- Women with a positive pregnancy test.
Trial locations and contacts
78 sites in 10 countries.
78 sites in 10 countries
France24 sites
Institut Saint Catherine
Avignon, 84918
Hôpital Avicenne
Bobigny, 93000
Institut Bergonié
Bordeaux, 33076
CHGU Morvan - Brest
Brest, 29200
Hôpital Louis Pradel
Bron, 69500
Centre Hospitalier de Cholet
Cholet, 49300
Hôpital intercommunal de Créteil
Créteil, 94010
CHU Grenoble
Grenoble, 38043
Clinique Victor Hugo
Le Mans, 72000
Centre Hospitalier du Mans
Le Mans, 72037
Hopital Albert Calmette
Lille, 59000
Paoli-Calmettes Institute
Marseille, 13273
CHU Montpellier
Montpellier, 34295
Hôpital Emile Muller
Mulhouse, 68100
Centre Catherine de Sienne
Nantes, 44277
Hôpital Saint-Louis
Paris, 75010
Hôpital Bichat - Claude-Bernard
Paris, 75018
Hôpital Tenon
Paris, 75970
Hôpital d'Instruction des Armées Bégin
Saint-Mandé, 94160
CHU de Strasbourg - Hôpital Civil
Strasbourg, 67091
Hôpital Larrey - CHU de Toulouse
Toulouse, 31059
Centre Hospitalier Régional Universitaire de Tours
Tours, 37044
Centre Hospitalier Troyes
Troyes, 10003
Institut Gustave Roussy (IGR)
Villejuif, 94805
Italy13 sites
IRCCS Oncologico Giovanni Paolo II
Bari, 70124
Unità Operativa di Oncologia dell'Ospedale Vito Fazzi di Lecce, Piazza Muratore
Lecce, 73100
Oncologia medica
Legnano, 37045
Azienda USL 2 Lucca - Dipartimento Oncologico
Lucca, 56124
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T)
Meldola, 47014
U.O.C. Pneumologia a indirizzo oncologico, Presidio Ospedaliero Monaldi - Azienda Ospedaliera dei Colli - Via Leonardo Bianchi
Naples, 80131
Istituto Oncologico Veneto, IRCCS
Padova, 35128
Ospedale di Perugia - Oncologia medica
Perugia, 06126
U.O. Oncologia Ospedale Infermi
Rimini, 47923
UOC di Oncologia Medica, Policlinico Universitario Campus Biomedico
Roma, 00128
IRCCS Regina Elena National Cancer Institute
Roma, 119
Policlinico Santa Maria alle Scotte
Siena, 53100
Ospedale Civile Maggiore
Verona, 37126
United States10 sites
BRCR Medical Center, Inc
Boca Raton, Florida, 33322
East Valley Hematology and Oncology medical Group
Burbank, California, 91505
Gabrail Cancer Center Research
Canton, Ohio, 44718
Pontchartrain Cancer Center
Covington, Louisiana, 70433
Gesinger Medical Center
Danville, Pennsylvania, 17822
Millenium Oncology
Houston, Texas, 77090
Meyer Cancer Center, Weill Cornell Medecine
New York, New York, 100001
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Robert W. Franz Cancer Center
Portland, Oregon, 97225
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Spain9 sites
"Complejo Hospitalario Universitario A Coruna (CHUAC)"
A Coruña, 15006
Hospital Universitari Quirón Dexeus
Barcelona, 08028
Hospital Universitari Vall D'Hebron
Barcelona, 08035
Hospital de Mataro
Barcelona, 08304
Hospital Universitario Germans Trias i Pujol
Barcelona, 08916
Hospital Universitario La Paz Servicio de Oncología Médica
Madrid, 28046
Hospital Universitario Puerta de Hierro Majadahonda Servicio de Oncología Médica Consultas externas, 2ª planta
Madrid, 28220
Hospital Universitario Carlos Haya
Málaga, 29010
Hospital de Mataro
Mataró, 08304
Hungary6 sites
Magyar Honvedseg Egeszsegugyi Kozpont II szamu telephely
Budapest, 1062
Országos Korányi TBC és Pulmonológiai Intézet XI Tüdőbelosztály
Budapest, 1121
Országos Korányi TBC és Pulmonológiai Intézet XIV Tüdőbelosztály
Budapest, 1121
Semmelweis Egyetem Altalanos Orvostudományi Kar Pulmonologiai Klinika
Budapest, 1125
Csongrad Megyei Mellkasi Betegsegek Szakkorháza I Tüdőosztály
Deszk, 6772
Matrai Gyogyintézet
Mátraháza, 3233
Israel5 sites
Soroka University Medical Center
Beersheba, 84101
Rambam Health Care Campus
Haifa, 3109601
Hadassah Campus Ein Kerem
Jerusalem, 9087200
Meir Medical Center
Kfar Saba, 44281
Rabin (Belinson) Medical Center
Petah Tikva, 4941492
Germany4 sites
Krankenhaus Mehrheit - Kliniken der Stadt Köln - Lungenklinik
Cologne, 51109
Klinik für Innere Medizin II Hospital Martha-Maria Halle-Dölau gGmbH
Halle, 06120
Universitätsklinikum Tübingen Medizinische Klinik II
Tübingen, 72076
Klinik für Innere Medizin II Universitätsklinikum Ulm
Ulm, 89081
Poland4 sites
Klinika Onkologii i Radioterapii , Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952
Przychodnia Lekarska "KOMED"
Konin, 62-500
Mazowieckie Centrum Leczenia chorób Płuc i Gruźlicy
Otwock
Wojewódzki Szpital Zespolony , Oddział Chemioterapii Nowotworów
Torun, 87-100
Czechia2 sites
Nemocnice Jihlava, Onkologické oddelení
Jihlava, 58633
Všeobecná Fakultní nemocnice
Prague, 12808
About this study
Official title: 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 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)
Read the detailed description
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).
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- OSE2101, Docetaxel, Pemetrexed
- Keywords
- Advanced Non-Small-Cell Lung Cancer, Therapeutic Cancer Vaccine, Resistance to Immunotherapy, Quality of Life
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OSE2101Biological
Also called TEDOPI, EP-2101, EP2101, IDM-2101
DocetaxelDrug
Also called Taxotere
PemetrexedDrug
Also called Alimta
| Study group | Role | What they receive |
|---|---|---|
| OSE2101 | Experimental | 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). Receives: Biological: OSE2101 |
| Docetaxel or Pemetrexed | Active comparator | 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. Receives: Drug: Docetaxel; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
OS defined as the time from randomisation to death from any cause in patients with ICI secondary resistance
Measured: Approx. 24 months
Secondary outcomes (7)
Post-Progression Survival
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
Measured: approximately 24 months
Time to Worsening ECOG PS
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.
Measured: Approx. 24 months
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
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
Measured: Approx. 24 months
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
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.
Measured: Approx. 24 months
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
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.
Measured: Approx. 24 months
Disease Control Rate (DCR) at 6 Months
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%)
Measured: Approx. 6 months
Progression Free Survival (PFS) in Patients With ICI Secondary Resistance
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)
Measured: Approx. 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2016 (estimated)
- Study start12 Feb 2016
- Primary completion15 Jan 2021
- Study completion15 Jan 2021
Why it stopped: due to COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- OSE Immunotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dominique Costantini, Dr, Study director, OSE Immunotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02654587
- Sponsor's protocol ID
- OSE2101C301
- Other IDs
- 2015-003183-36, 2015
- Acronym
- ATALANTE-1
- Status last verified
- Jan 2024
- First submitted
- 8 Jan 2016
- Last updated
- 2 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: 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
Publications
Besse B, Felip E, Garcia Campelo R, Cobo M, Mascaux C, Madroszyk A, Cappuzzo F, Hilgers W, Romano G, Denis F, Viteri S, Debieuvre D, Galetta D, Baldini E, Razaq M, Robinet G, Maio M, Delmonte A, Roch B, Masson P, Schuette W, Zer A, Remon J, Costantini D, Vasseur B, Dziadziuszko R, Giaccone G; ATALANTE-1 study group. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1. Ann Oncol. 2023 Oct;34(10):920-933. doi: 10.1016/j.annonc.2023.07.006. Epub 2023 Sep 11.
PubMed 37704166
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02654587
- Acronym / sponsor ID
- ATALANTE-1 / OSE2101C301
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- Advanced Non-Small-Cell Lung Cancer, Therapeutic Cancer Vaccine, Resistance to Immunotherapy, Quality of Life
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to COVID-19
- Enrolment
- 219 participants (actual)
- Lead sponsor
- OSE ImmunotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 12 Feb 2016 (actual)
- Primary completion
- 15 Jan 2021 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 13 Jan 2016 (estimated)
- Results
- Posted 2 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| OSE2101 | Experimental | Biological: OSE2101OSE2101 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). |
| Docetaxel or Pemetrexed | Active comparator | Drug: Docetaxel, Drug: PemetrexedPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Signed and dated informed consent
- Willingness and ability to comply with the clinical study procedures.
- Female or male, 18 years of age or older
- Histologically or cytologically proven diagnosis of Non-Small Cell Lung Cancer (NSCLC) that is locally advanced (stage III) unsuitable for radiotherapy or metastatic (stage IV) according to the 8th edition of tumor, node, metastasis (TNM) in Lung Cancer
- Subjects with disease recurrence or progression after immune checkpoint inhibitor and platinum-based chemotherapy:
Key exclusion criteria (19 listed)
- Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas)
- Patients with squamous cell carcinoma histology, and who had docetaxel as part of his prior chemotherapy
- Current or previous treatment with investigational therapy in another therapeutic clinical trial (interrupted less than 4 weeks before study treatment initiation)
- Patients whose tumor harbors EGFR gene mutation that sensitizes tumors to Tyrosine-Kinase Inhibitor (TKI) (EGFR exon 18-21) or Anaplastic Lymphoma Kinase (ALK) rearrangement
- Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OSE2101Also: TEDOPI, EP-2101, EP2101, IDM-2101 | Biological | OSE2101 |
| DocetaxelAlso: Taxotere | Drug | Docetaxel or Pemetrexed |
| PemetrexedAlso: Alimta | Drug | Docetaxel or Pemetrexed |
Primary outcome
Overall Survival (OS)
Time frame: Approx. 24 months
OS defined as the time from randomisation to death from any cause in patients with ICI secondary resistance
7 secondary outcomes
Post-Progression Survival
Time frame: approximately 24 months
Time to Worsening ECOG PS
Time frame: Approx. 24 months
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
Time frame: Approx. 24 months
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
Time frame: Approx. 24 months
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
Time frame: Approx. 24 months
Disease Control Rate (DCR) at 6 Months
Time frame: Approx. 6 months
Progression Free Survival (PFS) in Patients With ICI Secondary Resistance
Time frame: Approx. 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37704166Besse B, Felip E, Garcia Campelo R, Cobo M, Mascaux C, Madroszyk A, Cappuzzo F, Hilgers W, Romano G, Denis F, Viteri S, Debieuvre D, Galetta D, Baldini E, Razaq M, Robinet G, Maio M, Delmonte A, Roch B, Masson P, Schuette W, Zer A, Remon J, Costantini D, Vasseur B, Dziadziuszko R, Giaccone G; ATALANTE-1 study group. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1. Ann Oncol. 2023 Oct;34(10):920-933. doi: 10.1016/j.annonc.2023.07.006. Epub 2023 Sep 11.
- Link to the manuscript (free access)Link provided by the sponsor.
- Individual participant dataSharing planned: No. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Costantini, Dr study director
OSE Immunotherapeutics
78 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OSE2101, Docetaxel and Pemetrexed in people with Non Small Cell Lung Cancer, run by OSE Immunotherapeutics at 78 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in France, Italy, United States, Spain, Hungary and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Approx. 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02654587, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2024.