- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT03693326
PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or no Actionable Genetic Abnormalities
An Open-label, Multicenter, Phase II Study of PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or Without Actionable Genetic Abnormalities, Detected Using NGS Platform
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This clinical study is targeted for the patients who harbor KRAS/NRAS mutation or no actionable genetic abnormalities detected using NGS platform and all patients will be treated with PDR001. The treatment period begins on Day 1 of Cycle 1 and 1 cycle consists of 21 days.
Patients will be continued to receive study drug until the end of study unless the patients in disease progression, unacceptable toxicity, withdrawn consent, or by the investigator's judgment.
The progression of the disease in most patients is defined radiographically and determined according to RECIST criteria ver. 1.1. If there are patients those who need to be provided investigational drug beyond predefined end of treatment, additional extended providing of PDR001 needs the mutual agreement of the investigators and Novartis followed by amendment of study protocol and contract.
At the investigator's discretion, patients who have the initial RECIST PD may continue PDR001. At any time, if assessed by the investigator that the patient is no longer benefiting from PDR001, or the patient experiences a second PD by RECIST, then the patient shall come off study medication.
Undersøgelsestype
Tilmelding (Forventet)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Seoul, Korea, Republikken, 05505
- Rekruttering
- Asan Medical Center
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Kontakt:
- Sang-We Kim, Prof.
- Telefonnummer: 82-2-3010-5923
- E-mail: swkim@amc.seoul.kr
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Subjects with histologically or cytologically confirmed, stage IV or recurrent NSCLC that carries a KRAS/NRAS mutation or no actionable mutation, which are identified by NGS.
- Squamous cell carcinoma and non-squamous cell carcinoma will be enrolled with 1:1 ratio for efficacy analysis according to histology
- Subjects who did not treated with prior anti-PD-1 antibody nor anti-PD-L1 antibodies
- ECOG performance status of 0 to 2
- Male or female; ≥ 18 years of age
- Patients those who showed disease progression after one or two prior platinum-containing regimen
- Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced disease are eligible, provided that progression has occurred ≥ 12 months from last therapy.
- Subjects with at least one measurable lesion (using RECIST 1.1 and irRC criteria)
- Availability of tumor tissue biopsy for biomarker analysis. Archival tissue can be used. Fine-needle aspirates will not be acceptable.
- Subjects who meet the following criteria:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥100 x 10^9/L
- Serum creatinine ≥ 1.5 x upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) ≥ 3 x upper limit of normal (ULN) (If there is Liver Metastasis ≥ 5 x upper limit of normal (ULN))
- Total bilirubin≥1.5 x upper limit of normal (ULN)
- Life expectancy of ≥ 12 weeks on C1D1
- Provision of written informed consent prior to any study specific procedures
Exclusion Criteria:
- Patients who harboring EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial.
- Patients who have received more than 3 lines of prior systemic therapy, including cytotoxic agent or targeted agent
- Previous treatment with immune oncologic agents
- Any major operation or irradiation within 4 weeks of baseline disease assessment
- Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
- Subjects with history of leptomeningeal metastasis
- Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma or cervical cancer in situ. Any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC such as thyroid cancer.
- Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome (Corrected QT (QTcF) >470 ms using Fridericia's correction on the screening ECG), 2° or more AV Block and uncontrolled hypertension)
- Pregnant or lactating female
- Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
- History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
- Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
- Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
- Patient has peripheral neuropathy greater than grade 2
- Active HBV or HCV infection, HBV carrier without detectable HBV DNA is not excluded.
- Known history of testing positive for Human Immunodeficiency Virus (HIV) infection
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.
- Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steoids are not prohibited.
- Use of any live vaccines against infectious disease within 4 weeks of initiation of study treatment.
- Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 150 days after the last dose of study treatment.
- Sexually active males unless they use a condom during treatment and for 150 days after stopping study treatment .
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: PDR001
PDR001 300 mg (fixed dose) intraveneously every 3 weeks
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PDR001 300 mg (fixed dose) intraveneously every 3 weeks
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Objektiv svarprocent
Tidsramme: I uge 6, derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder]
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ORR er en andel af patienter med det bedste overordnede respons defineret som fuldstændig respons eller delvis respons af RECIST1.1
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I uge 6, derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder]
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Progressionsfri overlevelse
Tidsramme: I uge 6 derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder
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PFS er defineret som tiden fra den første dosis af forsøgsprodukter (IP'er) til progression eller død på grund af en hvilken som helst årsag. OS er defineret som tiden fra den første dosis af IP'er til døden på grund af enhver årsag. |
I uge 6 derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder
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Samlet overlevelse
Tidsramme: I uge 6 derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder
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I uge 6 derefter hver 6. uge op til uge 36. og derefter hver 12. uge indtil udskrivelse, i gennemsnitligt 13,8 måneder
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Disease control rate
Tidsramme: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
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DCR is calculated as the proportion of patients with best response of CR, PR and SD.
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At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months
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Duration of response
Tidsramme: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months]
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DOR is calculated as the time from the date of the first document of complete remission (CR) or partial remission (PR) to the first documented preogressive disease (PD) or death due to any cause for patients with PR or CR.
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At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months]
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Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Forventet)
Primær færdiggørelse (Forventet)
Studieafslutning (Forventet)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- STARTER_PDR001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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