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

NCT02654587 | Terminated Phase 3 Results DMC

• 2 other identifiers: OSE2101C3012015-003183-36
• Study Type: interventional
• Target: 219
• Locations: 10 countries
• Sites: 78

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)

Conditions

Non Small Cell Lung Cancer

Keywords

Advanced Non-Small-Cell Lung Cancer; Therapeutic Cancer Vaccine; Resistance to Immunotherapy; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

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

  Approx. 24 months

Secondary Outcomes (7)

• Post-Progression Survival

  approximately 24 months

• Time to Worsening ECOG PS

  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

  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

  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

  Approx. 24 months

Other Outcomes (3)

• Objective Response Rate (ORR) in ICI Secondary Resistance

  Approx. 24 months

• Percentage of Patients With Objective Response at 6 Months in ICI Secondary Resistance

  Approx. 6 months

• Time to Next Lung Cancer Therapy in ICI Secondary Resistance

  Approx. 24 months

Study Arms (2)

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).

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.

Drug: Docetaxel; Drug: Pemetrexed

Interventions

OSE2101 BIOLOGICAL

Also known as: TEDOPI, EP-2101, EP2101, IDM-2101

OSE2101

Docetaxel DRUG

Also known as: Taxotere

Docetaxel or Pemetrexed

Pemetrexed DRUG

Also known as: Alimta

Docetaxel or Pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• OSE Immunotherapeutics: lead

Study Sites (78)

East Valley Hematology and Oncology medical Group

Burbank, California, 91505, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

BRCR Medical Center, Inc

Boca Raton, Florida, 33322, United States

Location

Pontchartrain Cancer Center

Covington, Louisiana, 70433, United States

Location

Meyer Cancer Center, Weill Cornell Medecine

New York, New York, 100001, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Robert W. Franz Cancer Center

Portland, Oregon, 97225, United States

Location

Gesinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Millenium Oncology

Houston, Texas, 77090, United States

Location

Nemocnice Jihlava, Onkologické oddelení

Jihlava, 58633, Czechia

Location

Všeobecná Fakultní nemocnice

Prague, 12808, Czechia

Location

Institut Saint Catherine

Avignon, 84918, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

CHGU Morvan - Brest

Brest, 29200, France

Location

Hôpital Louis Pradel

Bron, 69500, France

Location

Centre Hospitalier de Cholet

Cholet, 49300, France

Location

Hôpital intercommunal de Créteil

Créteil, 94010, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

Hopital Albert Calmette

Lille, 59000, France

Location

Paoli-Calmettes Institute

Marseille, 13273, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Hôpital Emile Muller

Mulhouse, 68100, France

Location

Centre Catherine de Sienne

Nantes, 44277, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Hôpital Bichat - Claude-Bernard

Paris, 75018, France

Location

Hôpital Tenon

Paris, 75970, France

Location

Hôpital d'Instruction des Armées Bégin

Saint-Mandé, 94160, France

Location

CHU de Strasbourg - Hôpital Civil

Strasbourg, 67091, France

Location

Hôpital Larrey - CHU de Toulouse

Toulouse, 31059, France

Location

Centre Hospitalier Régional Universitaire de Tours

Tours, 37044, France

Location

Centre Hospitalier Troyes

Troyes, 10003, France

Location

Institut Gustave Roussy (IGR)

Villejuif, 94805, France

Location

Krankenhaus Mehrheit - Kliniken der Stadt Köln - Lungenklinik

Cologne, 51109, Germany

Location

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

Halle, 06120, Germany

Location

Universitätsklinikum Tübingen Medizinische Klinik II

Tübingen, 72076, Germany

Location

Klinik für Innere Medizin II Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Magyar Honvedseg Egeszsegugyi Kozpont II szamu telephely

Budapest, 1062, Hungary

Location

Országos Korányi TBC és Pulmonológiai Intézet XI Tüdőbelosztály

Budapest, 1121, Hungary

Location

Országos Korányi TBC és Pulmonológiai Intézet XIV Tüdőbelosztály

Budapest, 1121, Hungary

Location

Semmelweis Egyetem Altalanos Orvostudományi Kar Pulmonologiai Klinika

Budapest, 1125, Hungary

Location

Csongrad Megyei Mellkasi Betegsegek Szakkorháza I Tüdőosztály

Deszk, 6772, Hungary

Location

Matrai Gyogyintézet

Mátraháza, 3233, Hungary

Location

Soroka University Medical Center

Beersheba, 84101, Israel

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah Campus Ein Kerem

Jerusalem, 9087200, Israel

Location

Meir Medical Center

Kfar Saba, 44281, Israel

Location

Rabin (Belinson) Medical Center

Petah Tikva, 4941492, Israel

Location

IRCCS Oncologico Giovanni Paolo II

Bari, 70124, Italy

Location

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

Lecce, 73100, Italy

Location

Oncologia medica

Legnano, 37045, Italy

Location

Azienda USL 2 Lucca - Dipartimento Oncologico

Lucca, 56124, Italy

Location

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

Meldola, 47014, Italy

Location

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

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto, IRCCS

Padua, 35128, Italy

Location

Ospedale di Perugia - Oncologia medica

Perugia, 06126, Italy

Location

U.O. Oncologia Ospedale Infermi

Rimini, 47923, Italy

Location

UOC di Oncologia Medica, Policlinico Universitario Campus Biomedico

Roma, 00128, Italy

Location

IRCCS Regina Elena National Cancer Institute

Roma, 119, Italy

Location

Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

Ospedale Civile Maggiore

Verona, 37126, Italy

Location

Klinika Onkologii i Radioterapii , Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Przychodnia Lekarska "KOMED"

Konin, 62-500, Poland

Location

Mazowieckie Centrum Leczenia chorób Płuc i Gruźlicy

Otwock, Poland

Location

Wojewódzki Szpital Zespolony , Oddział Chemioterapii Nowotworów

Torun, 87-100, Poland

Location

"Complejo Hospitalario Universitario A Coruna (CHUAC)"

A Coruña, 15006, Spain

Location

Hospital Universitari Quirón Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital de Mataro

Barcelona, 08304, Spain

Location

Hospital Universitario Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario La Paz Servicio de Oncología Médica

Madrid, 28046, Spain

Location

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

Madrid, 28220, Spain

Location

Hospital de Mataro

Mataró, 08304, Spain

Location

Hospital Universitario Carlos Haya

Málaga, 29010, Spain

Location

Milton Keynes Hospital

Milton Keynes, MK6 5LD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37704166 RESULT

Related Links

• Link to the manuscript (free access)

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

IDM 2101; Docetaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

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).

Results Point of Contact

• Title: Chief Medical Officer Immuno-Oncology
• Organization: OSE Immunotherapeutics

contact@ose-immuno.com

+33 2 28 29 10 10

Study Officials

• Dominique Costantini, Dr

  OSE Immunotherapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 13, 2016
• Study Start: February 12, 2016
• Primary Completion: January 15, 2021
• Study Completion: January 15, 2021
• Last Updated: February 2, 2024
• Results First Posted: February 2, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (5); PL (4); HU (6); US (10); CZ (2); ES (9); FR (24); GB (1); IT (13); DE (4)