Étude de phase 2 randomisée, en double aveugle, contrôlée contre placebo, visant à évaluer l’efficacité et la sécurité d’emploi de l’inupadénant en association avec le carboplatine et le pémétrexed chez des adultes présentant un carcinome pulmonaire non à petites cellules non épidermoïde ayant progressé sous immunothérapie

Essai clinique

Type : Industriel
Statut : Ouvert
Phase : II
Étape du traitement : Stade métastatique 2ème ligne
Étape de prise en charge : Rechute
Date d'ouverture : 26/08/2022
Date clôture : 31/05/2025
Promoteur : iTeos Belgium SA
Progression du cancer: Loco-régional et à distance
Résumé :

In both Part 1 and Part 2, there are two nonsquamous NSCLC patient populations eligible for the study treatment: 1)patients with Stage III, non-resectable cancer that have received chemoradiotherapy, followed by durvalumab, and then have progressed; 2)patients who have received only first-line immunotherapy with anti-PD-L1 therapy, but no chemotherapy, in the metastatic setting, then progressed.

In Part 1, all participants receive open-label inupadenant with standard of care doses of carboplatin and pemetrexed. Carboplatin is given at q3week intervals for no more than 4 cycles; pemetrexed continues at q3week as prescribed by the Investigator. Inupadenant is given orally BID. Dose-limiting toxicities are monitored during the first 21 days of treatment and a modified 3+3 escalation method is utilized to determine the recommended phase 2 dose (RP2D). Imaging and safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

Part 2 is double-blinded, with subjects randomized 1:1 to receive the RP2D of inupadenant or matched placebo. All subjects receive the carboplatin and pemetrexed per standard of care. Imaging, safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

In both Parts 1 and 2, blood samples are drawn to further define the pharmacokinetic profile of inupadenant and biosamples are collected for additional exploratory analyses.

Domaines/spécialités :
  • Cancers thoraciques respiratoires
    • Cancer bronchique non à petites cellules
Pathologies :
  • Tumeur maligne des bronches et du poumon - Cim10 : C34
Liens externes :

Critères de population

Sexe : Homme et femme
Age minimum : 18 ans
Critères d’inclusion :
  1. Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology that has relapsed or progressed
  2. Measurable disease as defined by RECIST v1.1 criteria
  3. PD-L1 expression status available at or after the time of diagnosis of advanced or metastatic NSCLC disease
  4. Can provide existing biopsy taken within 2 years prior to entering trial or provide fresh biopsy

  5. Have relapsed or progressed after prior anti- PD-(L)1 therapy as follows:

    1. At least 12 weeks of treatment with only 1 line of anti-PD-(L)1 therapy (mono or combo) in the metastatic setting, without concomitant chemotherapy OR
    2. At least 12 weeks of single-agent durvalumab
  6. Adequate organ function
  7. ECOG performance status of 0 to 1.
Critères d’exclusion :
  1. Symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease.
  2. Presence of active second malignancy
  3. EGFR or ALK mutation. Participants with presence of other driver mutations are allowed if targeted therapy is not available as per local standard of care.
  4. Preexisting gastrointestinal disorders/conditions that may interfere with ingestion or absorption of oral medications.
  5. History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis, except for Grade 1 pneumonitis from prior chemoradiation therapy (Stage III patients).
  6. History of or active autoimmune disease requiring systemic treatment in the last 6 months or persistent immune-mediated toxicity caused by checkpoint inhibitor therapy > Grade 2
  7. Known active or chronic hepatitis B or C infection unless adequately treated for at least 4 weeks with no detectable viral load; known infection with human immunodeficiency virus (HIV) unless receiving antiretroviral therapy with well-controlled disease.
  8. History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior therapy.
  9. Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids.
  10. Active infection requiring systemic therapy ≤ 7 days prior to first dose of study treatment.
  11. Any other oncologic treatments administered ≤14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment. Also, ongoing adverse effects from such treatment > Grade 1 with the exception for alopecia and Grade 2 peripheral neuropathy.
  12. Non-study related minor surgical procedure ≤7 days, or major surgical procedure of ≤ 5 weeks prior to first dose of study treatment.
  13. Uncontrolled or significant cardiovascular disease
  14. History of allergy or hypersensitivity to any of the study treatments.
  15. Treatment with a live or live attenuated vaccine.
  16. Treatment with moderate or strong inducers or inhibitor of CYP 3A4, inhibitors of P-glycoprotein, or substrates of breast cancer resistance protein
  17. Pregnant or breast-feeding
  18. Male and Female participants: Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy

Centre d'investigation

En cours
Nom : Centre Georges François Leclerc - CGFL
Ville : DIJON (21)
RESPONSABLE MÉDICAL
Nom : Dr FAVIER
Prénom : Laure
Téléphone : Non disponible
Email : lfavier@cgfl.fr
CONTACT TECHNIQUE
Nom : PRZYBYL
Prénom : Pauline
Téléphone : 03 80 73 77 56
Email : pprzybyl@cgfl.fr

Référentiels Oncologik

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