Etude : MS201781-0031 / NHS-IL12 JAVELIN IL-12 COMBO



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : MS201781-0031

Nom : NHS-IL12 JAVELIN IL-12 COMBO

Traitement : Métastasique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 09/07/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase Ib de détermination de la dose, menée en ouvert, visant à évaluer la sécurité d’emploi, la tolérance et la pharmacocinétique de l’avélumab en association avec le M9241 (NHS-IL12) chez des patients atteints de tumeurs solides avancées, non résécables ou métastatiques

Spécialité : Voies urinaires
Localisation : C65 - Tumeur maligne du bassinet

Spécialité : Voies urinaires
Localisation : C66 - Tumeur maligne de l'uretère

Spécialité : Voies urinaires
Localisation : C67 - Tumeur maligne de la vessie
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The study consists of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase will evaluate the safety, tolerability, and PK of avelumab in combination with NHS-IL12 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase will assess the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who have completed the combination treatment of avelumab at a given dose level of NHS-IL12, a safety review will be performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects will be treated with escalating doses of NHS-IL12 with avelumab intravenous (IV).

Phase : Ib

Stade : III à IV

2, 3, 4, X
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : Part B:

- Availability of a fresh tumor biopsy is mandatory for eligibility in the RCC cohort. The biopsy or surgical specimen should be collected within 28 days prior to the first IMP administration. If a subject has 2 separate biopsy attempts in which usable tissue is not obtained, enrollment may be possible after discussion with the Medical Monitor. For other expansion cohorts, availability of either tumor archival material (< 6 months old) or fresh biopsies (obtained within 28 days) is acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor archival material must be suitable for biomarker assessment

- Urothelial carcinoma (UC) post-platinum: Histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra). Subjects must have progressed after treatment with at least 1 platinum containing regimen for inoperable locally advanced or metastatic UC or disease recurrence. Availability of either tumor archival material (< 6 months old)or fresh biopsies (obtained within 28 days) is acceptable with one of these being mandatory. For formalin-fixed paraffin-embedded samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor archival material must be suitable for biomarker assessment.

- Non-small cell lung cancer (NSCLC), first-line metastatic: Stage IV (per seventh International Association for the Study of Lung Cancer classification) histologically confirmed NSCLC. Subjects must not have received treatment for their metastatic disease. Subjects could have received adjuvant chemotherapy or loco-regional treatment that included chemotherapy for locally advanced disease, as long as disease recurrence occurred at least 6 months after the completion of the last administration of chemotherapy. Only epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type are allowed (ie, EGFR mutation and ALK translocation / re arrangement excluded). Non squamous cell histologies and never / former light smoker (< 15 pack years) squamous cell carcinoma subjects (per local standard of care) require testing if status is unknown. Subjects must have low tumor PD-L1 expression defined as < 50% tumor proportion score determined using PD-L1 IHC 22C3 pharmDx test or an equivalent Food and Drug Administration (FDA)- approved PD-L1 test. Availability of either tumor archival material or fresh biopsies within 28 days is acceptable with one of these being mandatory. For FFPE samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor archival material must be suitable for biomarker assessment. This cohort will not be opened for enrollment in Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom.

- Colorectal cancer (CRC): Histologically or cytologically confirmed recurrent or refractory metastatic CRC (according to American Joint Committee on Cancer / International Union Against Cancer Tumor Node Metastasis [TNM] Staging System seventh edition) after failure of prior therapy containing oxaliplatin / fluoropyrimidine and / or irinotecan / fluoropyrimidine and, if eligible, cetuximab (Erbitux®) and bevacizumab (Avastin®). Only subjects with microsatellite instability (MSI)-low or microsatellite stable (MSS) metastatic CRC are eligible. Subjects without existing MSI test results will have MSI status performed locally by a Clinical Laboratory Improvement Amendments (CLIA)-certified IHC or polymerase chain reaction (PCR)-based test (PCR based MSI test is preferred). Subjects must be willing to undergo an on-treatment biopsy procedure. Availability of either tumor archival material or fresh biopsies within 28 days is acceptable with one of these being mandatory. For FFPE samples, either block or sections (> 15) may be provided. Tumor biopsies and tumor archival material must be suitable for biomarker assessment. For Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Spain, and United Kingdom, subjects in the second-line setting should have exhausted or be considered ineligible or intolerant (in the opinion of the Investigator) of available second-line chemotherapy options.

- Renal cell carcinoma (RCC), primary immune checkpoint inhibitor failure: Histologically or cytologically documented metastatic RCC with a component of clear cell subtype. Subjects must have had progressive disease (PD) within 6 months or best overall response of stable disease (SD) for ≥ 6 months following start of therapy with any antibody / drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) for advanced or metastatic disease (either as monotherapy or combination therapy, in any line). Fresh tumor biopsy is required for enrollment. If a subject has 2 separate biopsy attempts in which usable tissue is not obtained, enrollment may be possible after discussion with the Medical Monitor. Subjects must be willing to undergo an on-treatment biopsy procedure. In France, in addition to having received checkpoint inhibitor therapy, subjects should have already received recommended local-standard therapy per the discretion of the Investigator.

Critères de non-inclusion : - Concurrent treatment with a non-permitted drug/intervention (listed below)
Anticancer treatment (eg, cytoreductive therapy, radiotherapy, immune therapy, cytokine therapy, monoclonal antibody, targeted small molecule therapy) or any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to start of trial treatment, or not recovered from adverse event (AE) related to such therapies, with the following exceptions: Palliative radiotherapy delivered in a normal organ-sparing technique is permitted; Erythropoietin, darbepoetin-α and granulocyte colony-stimulating factor are permitted; Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis are permitted (i.e. luteinizing hormone-releasing hormone agonist/antagonists). No other hormonal anticancer therapy is permitted.
- Major surgery (as deemed by Investigator) for any reason, except diagnostic biopsy, within 4 weeks prior to start of trial treatment, or not fully recovered from surgery within 4 weeks prior to start of trial treatment
- Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before start of trial treatment, with the following exceptions: Subjects with adrenal insufficiency, may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily; Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) is permitted; Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the dose after 14 days will be equivalent to <= 10 mg prednisone daily.
- Any prior treatment with any form of interlukin-12 (IL-12)
- For the NSCLC, CRC, and UC expansion cohorts, prior therapy with any antibody / drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anticytotoxic T lymphocyte antigen-4 (CTLA-4) antibody is prohibited.
- Intolerance to checkpoint inhibitor therapy, as defined by the occurrence of an AE requiring drug discontinuation.
- Active or history of primary or metastatic central nervous system tumors
- Prior organ transplantation, including allogeneic stem-cell transplantation
- Previous malignant disease (other than the indication for this trial) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to trial entry and the subject was deemed to have been cured with no additional therapy required or anticipated to be required.
- Significant acute or chronic infections requiring systemic therapy including, among others:
- History of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
- Hepatitis B or C infection (HBV surface antigen positive and HBV core antibody positive with reflex to positive HBV deoxy ribonucleic acid (DNA) or HBV core antibody positive alone with reflex to positive HBV DNA or positive hepatitis C virus [HCV] antibody with reflex to positive HCV ribonucleic acid [RNA]). Subjects with history of infection must have polymerase chain reaction documentation that infection is cleared.
- Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible if they are stable on other medical treatment and do not fulfill exclusion criterion including Uncontrolled intercurrent illness
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade>= 3 National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma)
- History of allergic reaction to methotrexate (trace methotrexate may be present in NHS-IL12 as a part of the manufacturing process) or history of severe hypersensitivity reaction to any other ingredient of the study drug(s) and / or their excipients. Since NHS-IL12 contains sucrose as an excipient, subjects suffering from hereditary fructose intolerance are also excluded
- Persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v4.03 with the following exceptions:
Neuropathy Grade <= 2 is acceptable.
All grades of alopecia are acceptable.
Endocrine dysfunction on replacement therapy is acceptable.
Pregnancy or lactation
Known alcohol or drug abuse as deemed by the Investigator
- Uncontrolled intercurrent illness including, but not limited to:
Hypertension uncontrolled by standard therapies (not stabilized to 150/90 millimeter of mercury (mm Hg) or lower)
Uncontrolled active infection
Uncontrolled diabetes (eg, glycosylated hemoglobin [HgbA1c] >= 8%)
- Clinically significant (or active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class >= II), or serious cardiac arrhythmia requiring medication
- All other significant diseases (eg, inflammatory bowel disease, current severe acute or chronic colitis) or chronic medical conditions (including laboratory abnormalities) that in the opinion of the Investigator might impair the subject's tolerance of trial treatment or interpretation of trial results.
- Any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with trial requirements.
- Legal incapacity or limited legal capacity.
- Administration of a live vaccine within 30 days prior to trial entry.
- Any subject with possible area of ongoing necrosis (non-disease related), such as active ulcer, non-healing wound, or intercurrent bone fracture that may be at risk of delayed healing due to protocol therapy.
- Oxygen saturation < 90% at rest, known pulmonary fibrosis, or active interstitial lung disease.
- History of congenital or active immunodeficiency, with the exception of acquired treatment-related hypogammaglobulinemia requiring periodic IV immunoglobulin infusion.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02994953
Promoteur :
EMD Serono Research & Development Institute, Inc.
Type de sponsor : Industriel
-
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Professeur Nicolas PENEL

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Ouverture de l'essai : OUVERT

MAJ : 09/07/2019