A phase 3 trial comparing a therapeutic cancer vaccine OSE2101 to chemotherapy docetaxel in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) after immunotherapy failure.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

OSE Immunotherapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Oct 2024 → ongoing

Decision date (initial)

2024-09-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To confirm the superiority of OSE2101 versus docetaxel on Overall Survival (OS)

Secondary objectives 1

1. To confirm the clinical benefit of OSE2101 versus docetaxel including Patient Reported Outcomes (PROs)

Conditions and MedDRA coding

Patients with HLA-A2 positive phenotype and metastatic Non-Small Cell Lung Cancer.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Male or female, aged ≥ 18 years
2. Patients expressing HLA-A2 phenotype in blood by pre-screening central laboratory
3. Patients with histologically or cytologically squamous or non-squamous documented NSCLC, metastatic stage at study entry, not eligible for definite surgery or radiation, without EGFR, ALK and ROS1 gene alterations eligible for targeted therapy; for patients with squamous NSCLC, the molecular tests are not mandatory if age ≥ 50 years old and smoker ≥ 15 pack years; other sensitizing mutations known to be immunosensitive are eligible in case of lack of local access to targeted therapy (i.e.; KRAS G12C and BRAF mutations) after Sponsor’ agreement
4. Patients with metastatic NSCLC who received only one prior line of systemic therapy with CT and ICI, with ICI lasting ≥ 24 weeks, including ≥ 12 weeks of anti-PD(L)1 as monotherapy or in combination with another ICI or an anti-angiogenic prior to randomization (i.e.; ICI secondary resistance); induction treatment with first-line CT-ICI should contain platinum-based CT
5. Patients that experience a radiologically documented PD (assessed by the Investigator) ≥ 24 weeks of ICI, including ≥ 12-weeks of anti-PD(L)1 as monotherapy or in combination with another ICI or an anti-angiogenic prior to randomization; patients who permanently stopped ICI after a protocol specified cessation of ICI according to site’ practice and patients after having permanently stopped ICI due to prior toxicity that is resolved or not clinically significant at time of study entry are authorized
6. Patients with ECOG performance status (PS) 0 or 1
7. Patients with measurable or non-measurable lesions per RECIST 1.1
8. Patients with adequate organ functions defined as: Albumin ≥ 2.8 g/dL ; AST and ALT up to 3.0 x ULN associated with Alkaline Phosphatase (ALKP) ≤ 2.5 x ULN, or ALPK ≥ 2.5 x ULN up to 5.0 x ULN associated with AST and ALT ≤ 1.5 x ULN ; Total serum bilirubin ≤ 1 x ULN; for patients with Gilbert’s syndrome, total bilirubin ≤ 3 ULN or direct bilirubin ≤ 1.5 ULN ; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L ; Platelets ≥ 100 x 109/L ; Haemoglobin ≥ 9 g/dL (in the absence of transfusion within 2 weeks before randomization) ; Creatinine clearance (CrCl) according to CKD-EPI (Chronic Kidney Disease – EPIdemiology) formula ≥ 30 ml/min/1.73m2
9. Patients without clinically significant ongoing toxicity from prior therapy (severity ≤ Grade 1; except alopecia) ; patients with disease necessitating a replacement treatment and well balanced are authorized (e.g., hypo or hyperthyroidism, adrenal insufficiency, diabetes treated by oral anti-glycemic agent and/or insulin therapy…)
10. If applicable, before study treatment (OSE2101 or docetaxel) administration, a wash out of at least 21 days or 5 half-lives (whichever is shorter) since the last anticancer treatment or investigational therapy; a wash out of at least 28 days after definitive radiation or prior major surgery; wash out after palliative radiation of at least 2 weeks
11. Women of childbearing potential (WOCBP) participating in the study must agree to use highly effective methods of contraception (i.e., one that results in a less than 1% per year failure rate when used consistently and correctly) prior to study entry, during the study, and for 180 days after the last dose of study treatment. Highly effective methods of contraception are defined as one of the following methods: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence
12. Male patient with WOCBP partner must be willing to use male contraception (condoms) during the study, and for 90 days after the last dose of study treatment. WOCBP partners of male subjects participating in the study may use hormone-based contraceptives as one of the acceptable methods of contraception since they will not be receiving the study treatment (i.e.; oral hormonal contraception, cap, diaphragm, or sponge with spermicide)
13. WOCBP must have a highly sensitive or serum pregnancy negative test during screening and within 24 hours prior to each administration of the study treatment (OSE2101 or docetaxel). Women who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilised do not require this test
14. Patients having signed and dated informed consent (IC) prior to any trial-specific procedures
15. Patients must be affiliated to a social security system per local regulation (such as in France).

Exclusion criteria 15

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 active auto-immune disease and/or immune-related disease due to prior immunotherapy or other condition requiring systemic immunosuppressive treatments or chronic administration of corticosteroids > 10 mg daily prednisolone equivalent (except as replacement if adrenal insufficiency); short course of corticosteroids > 10 mg daily prednisolone equivalent is allowed if ≤ 10 days continuous duration (e.g. premedication to prevent contrast allergy, drug reaction…); topical, ocular, intra-articular, intranasal, and inhaled corticosteroids with minimal systemic absorption are allowed
3. Patients with interstitial lung disease or active non-infectious pneumonitis
4. Patients who have known hereditary, congenital or acquired immunodeficiencies; for human immunodeficiency virus (HIV) infection, patient may be eligible if CD4+ count ≥ 350 cells/μL, and no history of acquired immunodeficiency syndrome (AIDS) infections within 12 months prior to start of study treatment, and receiving an established antiretroviral therapy with NO known drug-drug interaction with docetaxel for at least 4 weeks prior to starting the study treatment, and have a viral load ≤ 400 copies/μL (local laboratory)
5. Patients with an active infection requiring anti-infective therapy until all signs of infection have resolved before randomization
6. Patients with PD during induction first-line CT-ICI (to exclude hyper progression and fast progression to CT-ICI) or with PD within 24 weeks of ICI; chemotherapy or other cytotoxic agents in combination with ICI within 12 weeks prior to randomization are not authorized;
7. Patients with chronic Hepatitis B (HBV) infection who meet the criteria for antiviral therapy (according to local/international guidelines) and not treated prior to starting the study treatment; patients with an active Hepatitis C (HCV) with HCV viral load (by local laboratory) above the limit of quantification; patients who received a prior antiviral HCV treatment or no prior treatment but HCV natural resolution with HCV RNA not detectable are eligible
8. Patients with other active cancer(s) within 3 years prior to randomization (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)
9. Patients with severe acute or chronic medical (i.e., severe liver impairment) or psychiatric or incapacitated conditions, or laboratory abnormalities that would expose to an excess risk associated with study participation or study drug administration in the opinion of the Investigator and/or the Sponsor
10. Patient participating in another clinical trial with an investigational medicinal product
11. Patient is the Principal Investigator or Investigator, research assistant, pharmacist, study coordinator, other staff directly involved in the conduct of the study
12. Patients with known hypersensitivity to the active substances or to any of the excipients of OSE2101 or docetaxel
13. Patients with current brain metastases, leptomeningeal metastases or carcinomatous meningitis, or previously treated brain metastases, leptomeningeal metastases, or carcinomatous meningitis; patients with spinal cord compression except if due to external causes and duly treated (e.g.; radiation for bone metastasis)
14. Patients with AST and/or ALT >1.5 × ULN concomitant with ALPK > 2.5 × ULN
15. Pregnant or breastfeeding woman.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS defined as time from randomization to death of any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

OSE Immunotherapeutics

Sponsor organisation

OSE Immunotherapeutics

Address

22 Boulevard Benoni Goullin

City

Nantes

Postcode

44200

Country

France

Scientific contact point

Organisation

OSE Immunotherapeutics

Contact name

Caroline CHEVALIER

Public contact point

Organisation

OSE Immunotherapeutics

Contact name

Caroline CHEVALIER

Third parties 16

Locations

11 EU/EEA countries · 122 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 146 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

31 submissions — initial application plus substantial / non-substantial modifications