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

Non Small Cell Lung Cancer Clinical Trial

— ATALANTE-1  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02654587
• Other study ID #: OSE2101C301
• Secondary ID: 2015-003183-36
• Status: Terminated
• Phase: Phase 3
• Start date: February 12, 2016
• Est. completion date: January 15, 2021

Study information

• Verified date: January 2024
• Source: OSE Immunotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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)

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 219
• Est. completion date: January 15, 2021
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Biological:
• OSE2101

Drug:
• Docetaxel

• Pemetrexed

Locations

Country	Name	City	State
Czechia	Nemocnice Jihlava, Onkologické oddelení	Jihlava
Czechia	Všeobecná Fakultní nemocnice	Praha
France	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	Centre Hospitalier du Mans	Le Mans
France	Clinique Victor Hugo	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 Bichat - Claude-Bernard	Paris
France	Hôpital Saint-Louis	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
Germany	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	Tubingen
Germany	Klinik für Innere Medizin II Universitätsklinikum Ulm	Ulm
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont II szamu telephely	Budapest
Hungary	Országos Korányi TBC és Pulmonológiai Intézet XI Tüdobelosztály	Budapest
Hungary	Országos Korányi TBC és Pulmonológiai Intézet XIV Tüdobelosztály	Budapest
Hungary	Semmelweis Egyetem Altalanos Orvostudományi Kar Pulmonologiai Klinika	Budapest
Hungary	Csongrad Megyei Mellkasi Betegsegek Szakkorháza I Tüdoosztály	Deszk
Hungary	Matrai Gyogyintézet	Mátraháza
Israel	Soroka University Medical Center	Be'er Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Campus Ein Kerem	Jerusalem
Israel	Meir Medical Center	Kefar Saba
Israel	Rabin (Belinson) Medical Center	Petah tikva
Italy	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	Padova
Italy	Ospedale di Perugia - Oncologia medica	Perugia
Italy	U.O. Oncologia Ospedale Infermi	Rimini
Italy	IRCCS Regina Elena National Cancer Institute	Roma
Italy	UOC di Oncologia Medica, Policlinico Universitario Campus Biomedico	Roma
Italy	Policlinico Santa Maria alle Scotte	Siena
Italy	Ospedale Civile Maggiore	Verona
Poland	Klinika Onkologii i Radioterapii , Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Przychodnia Lekarska "KOMED"	Konin
Poland	Mazowieckie Centrum Leczenia chorób Pluc i Gruzlicy	Otwock
Poland	Wojewódzki Szpital Zespolony , Oddzial Chemioterapii Nowotworów	Torun
Spain	Hospital de Mataro	Barcelona
Spain	Hospital Universitari Quirón Dexeus	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario Germans Trias i Pujol	Barcelona
Spain	"Complejo Hospitalario Universitario A Coruna (CHUAC)"	La Coruña
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 Universitario Carlos Haya	Málaga
Spain	Hospital de Mataro	Mataró
United Kingdom	Milton Keynes Hospital	Milton Keynes
United States	BRCR Medical Center, Inc	Boca Raton	Florida
United States	East Valley Hematology and Oncology medical Group	Burbank	California
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Pontchartrain Cancer Center	Covington	Louisiana
United States	Gesinger Medical Center	Danville	Pennsylvania
United States	Millenium Oncology	Houston	Texas
United States	Meyer Cancer Center, Weill Cornell Medecine	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Robert W. Franz Cancer Center	Portland	Oregon
United States	Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
OSE Immunotherapeutics

Countries where clinical trial is conducted

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

References & 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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Objective Response Rate (ORR) in ICI Secondary Resistance	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.	Approx. 24 months
Other	Percentage of Patients With Objective Response at 6 Months in ICI Secondary Resistance	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	Approx. 6 months
Other	Time to Next Lung Cancer Therapy in ICI Secondary Resistance	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	Approx. 24 months
Primary	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	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	approximately 24 months
Secondary	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.	Approx. 24 months
Secondary	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	Approx. 24 months
Secondary	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.	Approx. 24 months
Secondary	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.	Approx. 24 months
Secondary	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%)	Approx. 6 months
Secondary	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)	Approx. 24 months

External Links

•   Link to the manuscript (free access)