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

NCT ID: NCT02654587

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-12
• Study Completion Date: 2021-01-15

Brief 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 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).

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OSE2101

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).

Group Type: EXPERIMENTAL

OSE2101

Intervention Type: BIOLOGICAL

Docetaxel or Pemetrexed

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.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Interventions

OSE2101

Intervention Type: BIOLOGICAL

Docetaxel

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Other Intervention Names

TEDOPI; EP-2101; EP2101; IDM-2101; Taxotere; Alimta

Eligibility Criteria

Inclusion Criteria

1. Signed and dated informed consent

2. Willingness and ability to comply with the clinical study procedures.

3. Female or male, 18 years of age or older

4. 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

5. Subjects with disease recurrence or progression after immune checkpoint inhibitor and platinum-based chemotherapy:

i) 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

6. Subjects with measurable or non-measurable lesions according to RECIST 1.1

7. Subjects must express HLA-A2 phenotype (central test in blood)

8. Subjects must be considered suitable for chemotherapy with single-agent pemetrexed or single-agent docetaxel

9. 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

10. Any prior chemotherapy, immunotherapy, hormonal therapy, radiation therapy or surgeries must have been completed at least 3 weeks prior to initiation of study treatment.

11. Any toxicity from prior therapy must have recovered to ≤ Grade 1 (except alopecia)

12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

13. 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.

Exclusion Criteria

1. Small-cell lung cancer/mixed NSCLC with small cell component or other neuroendocrine lung cancers (typical and atypical carcinoids, large-cell neuroendocrine carcinomas)

2. Patients with squamous cell carcinoma histology, and who had docetaxel as part of his prior chemotherapy

3. Current or previous treatment with investigational therapy in another therapeutic clinical trial (interrupted less than 4 weeks before study treatment initiation)

4. 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

5. Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)

6. Spinal cord compression (unless treated with the patient attaining good pain control and stable or recovered neurologic function), carcinomatous meningitis, or leptomeningeal disease

7. 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)

8. Patients with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications

9. 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

10. 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)

11. Patients with auto-immune disease, with the exception of type I diabetes or treated hypothyroidism

12. Patients with interstitial lung disease

13. Patients with active B or C hepatitis

14. 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)

15. 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

16. 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

17. 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

18. Breastfeeding women

19. Women with a positive pregnancy test.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OSE Immunotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominique Costantini, Dr

Role: STUDY_DIRECTOR

OSE Immunotherapeutics

Locations

East Valley Hematology and Oncology medical Group

Burbank, California, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

BRCR Medical Center, Inc

Boca Raton, Florida, United States

Pontchartrain Cancer Center

Covington, Louisiana, United States

Meyer Cancer Center, Weill Cornell Medecine

New York, New York, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Robert W. Franz Cancer Center

Portland, Oregon, United States

Gesinger Medical Center

Danville, Pennsylvania, United States

Millenium Oncology

Houston, Texas, United States

Nemocnice Jihlava, Onkologické oddelení

Jihlava, , Czechia

Všeobecná Fakultní nemocnice

Prague, , Czechia

Institut Saint Catherine

Avignon, , France

Hôpital Avicenne

Bobigny, , France

Institut Bergonié

Bordeaux, , France

CHGU Morvan - Brest

Brest, , France

Hôpital Louis Pradel

Bron, , France

Centre Hospitalier de Cholet

Cholet, , France

Hôpital intercommunal de Créteil

Créteil, , France

CHU Grenoble

Grenoble, , France

Clinique Victor Hugo

Le Mans, , France

Centre Hospitalier du Mans

Le Mans, , France

Hopital Albert Calmette

Lille, , France

Paoli-Calmettes Institute

Marseille, , France

CHU Montpellier

Montpellier, , France

Hôpital Emile Muller

Mulhouse, , France

Centre Catherine de Sienne

Nantes, , France

Hôpital Saint-Louis

Paris, , France

Hôpital Bichat - Claude-Bernard

Paris, , France

Hôpital Tenon

Paris, , France

Hôpital d'Instruction des Armées Bégin

Saint-Mandé, , France

CHU de Strasbourg - Hôpital Civil

Strasbourg, , France

Hôpital Larrey - CHU de Toulouse

Toulouse, , France

Centre Hospitalier Régional Universitaire de Tours

Tours, , France

Centre Hospitalier Troyes

Troyes, , France

Institut Gustave Roussy (IGR)

Villejuif, , France

Krankenhaus Mehrheit - Kliniken der Stadt Köln - Lungenklinik

Cologne, , Germany

Klinik für Innere Medizin II Hospital Martha-Maria Halle-Dölau gGmbH

Halle, , Germany

Universitätsklinikum Tübingen Medizinische Klinik II

Tübingen, , Germany

Klinik für Innere Medizin II Universitätsklinikum Ulm

Ulm, , Germany

Magyar Honvedseg Egeszsegugyi Kozpont II szamu telephely

Budapest, , Hungary

Országos Korányi TBC és Pulmonológiai Intézet XI Tüdőbelosztály

Budapest, , Hungary

Országos Korányi TBC és Pulmonológiai Intézet XIV Tüdőbelosztály

Budapest, , Hungary

Semmelweis Egyetem Altalanos Orvostudományi Kar Pulmonologiai Klinika

Budapest, , Hungary

Csongrad Megyei Mellkasi Betegsegek Szakkorháza I Tüdőosztály

Deszk, , Hungary

Matrai Gyogyintézet

Mátraháza, , Hungary

Soroka University Medical Center

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Hadassah Campus Ein Kerem

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Rabin (Belinson) Medical Center

Petah Tikva, , Israel

IRCCS Oncologico Giovanni Paolo II

Bari, , Italy

Unità Operativa di Oncologia dell'Ospedale Vito Fazzi di Lecce, Piazza Muratore

Lecce, , Italy

Oncologia medica

Legnano, , Italy

Azienda USL 2 Lucca - Dipartimento Oncologico

Lucca, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T)

Meldola, , Italy

U.O.C. Pneumologia a indirizzo oncologico, Presidio Ospedaliero Monaldi - Azienda Ospedaliera dei Colli - Via Leonardo Bianchi

Napoli, , Italy

Istituto Oncologico Veneto, IRCCS

Padua, , Italy

Ospedale di Perugia - Oncologia medica

Perugia, , Italy

U.O. Oncologia Ospedale Infermi

Rimini, , Italy

UOC di Oncologia Medica, Policlinico Universitario Campus Biomedico

Roma, , Italy

IRCCS Regina Elena National Cancer Institute

Roma, , Italy

Policlinico Santa Maria alle Scotte

Siena, , Italy

Ospedale Civile Maggiore

Verona, , Italy

Klinika Onkologii i Radioterapii , Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Przychodnia Lekarska "KOMED"

Konin, , Poland

Mazowieckie Centrum Leczenia chorób Płuc i Gruźlicy

Otwock, , Poland

Wojewódzki Szpital Zespolony , Oddział Chemioterapii Nowotworów

Torun, , Poland

"Complejo Hospitalario Universitario A Coruna (CHUAC)"

A Coruña, , Spain

Hospital Universitari Quirón Dexeus

Barcelona, , Spain

Hospital Universitari Vall D'Hebron

Barcelona, , Spain

Hospital de Mataro

Barcelona, , Spain

Hospital Universitario Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario La Paz Servicio de Oncología Médica

Madrid, , Spain

Hospital Universitario Puerta de Hierro Majadahonda Servicio de Oncología Médica Consultas externas, 2ª planta

Madrid, , Spain

Hospital de Mataro

Mataró, , Spain

Hospital Universitario Carlos Haya

Málaga, , Spain

Milton Keynes Hospital

Milton Keynes, , United Kingdom

Countries

United States; Czechia; France; Germany; Hungary; Israel; Italy; Poland; Spain; United Kingdom

References

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.

Reference Type: RESULT

PMID: 37704166 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://doi.org/10.1016/j.annonc.2023.07.006

Link to the manuscript (free access)

Other Identifiers

2015-003183-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OSE2101C301

Identifier Type: -

Identifier Source: org_study_id