OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure (ATALANTE-1)

• ClinicalTrials.gov Identifier: NCT02654587
• Recruitment Status: Terminated
• First Posted: January 13, 2016
• Results First Posted: February 2, 2024
• Last Update Posted: February 2, 2024
• Sponsor: OSE Immunotherapeutics
• Information provided by (Responsible Party): OSE Immunotherapeutics

Tracking Information

• First Submitted Date: January 8, 2016
• First Posted Date: January 13, 2016
• Results First Submitted Date: October 30, 2023
• Results First Posted Date: February 2, 2024
• Last Update Posted Date: February 2, 2024
• Actual Study Start Date: February 12, 2016
• Actual Primary Completion Date: January 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2024)

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

• Original Primary Outcome Measures (submitted: January 12, 2016): Overall Survival time (OS) [ Time Frame: Approximatively 24 months ]

Current Secondary Outcome Measures (submitted: January 31, 2024)

• Post-Progression Survival [ Time Frame: approximately 24 months ]
  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 [ Time Frame: Approx. 24 months ]
  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 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 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 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 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 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 ]
  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.
• Disease Control Rate (DCR) at 6 Months [ Time Frame: Approx. 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%)
• Progression Free Survival (PFS) in Patients With ICI Secondary Resistance [ Time Frame: Approx. 24 months ]
  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)

Original Secondary Outcome Measures (submitted: January 12, 2016)

• Progression-Free Survival (PFS) [ Time Frame: Approximatively 24 months ]
• QLQ-C30 global score [ Time Frame: Approximatively 24 months ]
• QLQ-LC13 global score [ Time Frame: Approximatively 24 months ]
• Objective Response Rate (ORR) [ Time Frame: Approximatively 24 months ]
• Patient Reported Outcomes (PRO) [ Time Frame: Approximatively 24 months ]

Current Other Pre-specified Outcome Measures (submitted: January 31, 2024)

• Objective Response Rate (ORR) in ICI Secondary Resistance [ Time Frame: Approx. 24 months ]
  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.
• Percentage of Patients With Objective Response at 6 Months in ICI Secondary Resistance [ Time Frame: Approx. 6 months ]
  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 in ICI Secondary Resistance [ Time Frame: Approx. 24 months ]
  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

Original Other Pre-specified Outcome Measures (submitted: January 12, 2016)

• Disease Control Rate (DCR) [ Time Frame: Approximatively 24 months ]
• Duration of Response (DR) [ Time Frame: Approximatively 24 months ]
• Time to deterioration (TTD) [ Time Frame: Approximatively 24 months ]
• Time to next lung cancer therapy [ Time Frame: Approximatively 24 months ]
• Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities [ Time Frame: Approximatively 48 months ]
  Safety and tolerability of OSE2101 compared to pemetrexed or docetaxel

Descriptive Information

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

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).
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

• Condition: Non Small Cell Lung Cancer

Intervention

• Biological: OSE2101
  Other Names:

  • TEDOPI
  • EP-2101
  • EP2101
  • IDM-2101
• Drug: Docetaxel
  Other Name: Taxotere
• Drug: Pemetrexed
  Other Name: Alimta

Study Arms

• Experimental: 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).
  Intervention: Biological: OSE2101
• Active Comparator: 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.

  Interventions:

  • Drug: Docetaxel
  • Drug: Pemetrexed

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 31, 2024): 219
• Original Estimated Enrollment (submitted: January 12, 2016): 500
• Actual Study Completion Date: January 15, 2021
• Actual Primary Completion Date: January 15, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, France, Germany, Hungary, Israel, Italy, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02654587
• Other Study ID Numbers: OSE2101C301; 2015-003183-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: 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

• Current Responsible Party: OSE Immunotherapeutics
• Original Responsible Party: Orphan Synergy Europe - Pharma
• Current Study Sponsor: OSE Immunotherapeutics
• Original Study Sponsor: Orphan Synergy Europe - Pharma
• Collaborators: Not Provided

Investigators

• Study Director: Dominique Costantini, Dr; OSE Immunotherapeutics

• PRS Account: OSE Immunotherapeutics
• Verification Date: January 2024