J3M-MC-JZQB - A Multicenter, Randomized, Phase 3 Study Comparing LY3537982 and Pembrolizumab to Placebo and Pembrolizumab as First-Line Treatment in Patients with KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer with high PD-L1 expression (TPS ≥ 50%).

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC and not suitable for curative intent radical surgery or radiation therapy. Staging will be according to the AJCC Staging System (8th ed [Lim W et al. 2018]).
- Must have disease with evidence of KRAS G12C mutation determined in tumor tissue by the investigational assay, described in Section 2.2.3, by the sponsor-designated central laboratory
- Must have a tumor with high PD-L1- expression (TPS ≥ 50%) as determined by IHC at the sponsor-designated central laboratory.
- Must have measurable disease per RECIST v1.1 (Eisenhauer et al. 2009) as assessed by the investigator. Target lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions, and the location of previously irradiated lesions is clearly documented
- Must have an ECOG performance status of 0 to 1 (Oken et al. 1982)
- Estimated life expectancy ≥ 12 weeks.
- Ability to swallow capsules.
- Specimens must be collected within 14 days before the start of study intervention. Must have adequate laboratory parameters.

Criteri di esclusione: 

- Have additional validated oncogenic drivers in NSCLC, if known: e.g., activating alterations in genes such as EGFR, ALK, BRAF (V600E), MET (exon 14), ROS1, RET, or NTRK1/2/3.
- Have untreated active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are completed prior CNS-directed therapy (including radiation and/or surgery) =28 days prior to the first dose of study intervention, and symptomatically and radiologically stable disease (i.e., without evidence of progression for = 28 days by repeat imaging). Clinically stable without requirement of steroid treatment within 14 days prior to randomization.
- Prophylactic anticonvulsants are permitted, provided the patient is on a stable dose for = 14 days prior to C1D1.
- Have clinically significant active cardiovascular disease or history of myocardial infarction or unstable angina within 6 months prior to planned start of study intervention.
- Have prolongation of the QT interval corrected for heart rate using Fridericia’s formula (QTcF) >470 msec. If QTcF >470 msec on more than 1 ECG is obtained during the screening repeat 2 additional times and use the average to determine eligibility. Note that patients with implanted pacemakers may enter study without meeting QTc criteria due to nonevaluable measurement.
-Have uncontrolled, disease-related, pericardial effusion or pleural effusion.
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- History of allogenic tissue/solid organ transplant.
- Have an active fungal, bacterial, and/or active untreated viral infection, including HIV or viral (A, B, or C) hepatitis (screening is not required unless mandated by local health authority).
    a. HIV-infected participants must be on ART and have a well-controlled HIV infection/disease defined as:
        i. Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at time of Screening
        ii. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of Screening and for at least 12 weeks prior to Screening
        iii. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 28 days prior to study entry (Day 1).
        iv. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease are excluded.
    b. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 28 days and have undetectable HBV viral load prior to randomization.
Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.
    c. Hepatitis B screening tests are not required unless:
        i. Known history of HBV infection
        ii. As mandated by local health authority
    d. Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening.
Note: Participants must have completed curative antiviral therapy at least 28 days prior to randomization.
    e. Hepatitis C screening tests are not required unless:
        i. Known history of HCV infection
        ii. As mandated by local health authority
- The patient has a serious preexisting medical condition(s) (such as known psychiatric or substance abuse disorder) that, in the judgment of the investigator, would preclude participation in this study, including severe dyspnea at rest, or requiring oxygen therapy.
- Screening for chronic conditions is not required.
- Have clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Patients receiving adjuvant hormone therapy for breast or prostate cancer with no evidence of disease are eligible.

Trattamento sperimentale: 

LY3537982

Trattamento di controllo: 

Pembrolizumab + Placebo

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-503412-33-00

Data di inserimento: 30.04.2024

Data di aggiornamento: 28.05.2024

Promotore

Eli Lilly and Company

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd