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JOURNAL ONKOLOGIE – STUDIE

Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC

Rekrutierend

NCT-Nummer:
NCT03333343

Studienbeginn:
Januar 2018

Letztes Update:
05.05.2021

Wirkstoff:
EGF816, LXH254, INC280, Trametinib, Ribociclib, Gefitinib

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Chair
Novartis

Kontakt

Studienlocations
(3 von 11)

Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
M5G 2M9 Toronto
CanadaAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
Shatin, New Territories
Hong KongAbgeschlossen» Google-Maps
Novartis Investigative Site
60126 Ancona
ItalyAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
20162 Milano
ItalyAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
119228 Singapore
SingaporeAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
169610 Singapore
SingaporeAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
70403 Tainan
TaiwanAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

This is a Phase Ib, open label, non-randomized dose escalation study of EGF816 in combination

with ribociclib, trametinib, or LXH254, followed by dose expansion of EGF816 in combination

with ribociclib, trametinib, LXH254, INC280, or gefitinib in adult patients with advanced

EGFR-mutant NSCLC.

During the dose escalation part, patients will be assigned to the addition of trametinib,

ribociclib, or LXH254 to EGF816.

Following determination of the recommended dose for the combination of EGF816 + trametinib,

EGF816 + ribociclib, and EGF816 + LXH254, patients may be enrolled to the dose expansion arms

of each of these combinations. Patients may also be assigned to EGF816 + INC280 or EGF816 +

gefitinib in dose expansion.

Efficacy assessments will be performed at baseline and every 2 cycles during treatment.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed locally advanced (stage

IIIB) or metastatic (stage IV) EGFR mutant (ex19del, L858R) NSCLC.

- Requirements of EGFR mutation status and prior lines of treatment:

- Treatment naive patients, who have locally advanced or metastatic NSCLC with EGFR

sensitizing mutation (e.g., L858R and/or ex19del), have not received any systemic

antineoplastic therapy for advanced NSCLC and are eligible to receive EGFR TKI

treatment. Patients with EGFR exon 20 insertion/duplication are not eligible. Note:

patients who have received only one cycle of chemotherapy in the advanced setting are

allowed.

- Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation

AND an acquired T790M mutation (e.g., L858R and/or ex19del, T790M+) following

progression on prior treatment with a 1st-generation EGFR TKI or 2nd-generation EGFR

TKI. These patients may not have received more than 4 prior lines of antineoplastic

therapy in the advanced setting, including EGFR TKI, and may not have received any

agent targeting EGFR T790M mutation (i.e., 3rd-generation EGFR TKI).

- Patients who have locally advanced or metastatic NSCLC with EGFR sensitizing mutation

and a "de novo" T790M mutation (i.e., no prior treatment with any agent known to

inhibit EGFR including EGFR TKI). These patients may not have received more than 3

prior lines of antineoplastic therapy in the advanced setting, and may not have

received any prior 3rd generation EGFR TKI.

- Patients must have a site of disease amenable to biopsy, and be a candidate for tumor

biopsy according to the treating institution's guidelines. Patients must be willing to

undergo a new tumor biopsy during therapy on this study, and at screening if an

archival tumor sample obtained since the diagnosis of advanced disease (1L patients)

or since last treatment failure (2L+ patients) is not available.

Exclusion Criteria:

- Patients with a history or presence of interstitial lung disease or interstitial

pneumonitis, including clinically significant radiation pneumonitis.

- Patients with unstable brain metastases.

- Patients with a history of another malignancy.

- Patients with a known history of human immunodeficiency virus (HIV) seropositivity.

- Patients with clinically significant, uncontrolled heart disease.

- Patients participating in additional parallel investigational drug or medical device

studies.

- Prior therapies:

- Patients who have been treated with EGFR TKI in the adjuvant setting within 6 months,

unless acquired EGFR T790M is present in a tumor or blood sample obtained since the

discontinuation of the EGFR TKI.

- Patients who have been treated with prior EGFR TKI targeting T790M (3rd generation).

- Patients who have been treated with systemic anti-neoplastic therapy within:

- 2 weeks for fluoropyrimidine monotherapy

- 6 weeks for nitrosoureas and mitomycin

- 4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy

(including monoclonal antibodies) and continuous or intermittent small molecule

therapeutics or any other investigational agent

Studien-Rationale

Primary outcome:

1. Number of patients with adverse events and serious adverse events (Time Frame - Every day until study end, approximately 4 years):
Assess safety and tolerability including incidence of dose limiting toxicities, adverse events, and serious adverse events.

2. ORR2 (Time Frame - Every 8-12 weeks until study ends, approximately 4 years):
Modified objective response rate (ORR2) per RECIST v1.1 (taking as baseline the most recent assessment prior to initiating combination)

Secondary outcome:

1. ORR (Time Frame - Every 8-12 weeks until study ends, approximately 4 years):
Overall response rate (ORR) per RECIST v1.1

2. PFS (Time Frame - Every 8-12 weeks until study ends, approximately 4 years):
Time from the date of first dose of study treatment to the date of first documented disease progression (per RECIST v1.1) or death due to any cause

3. DCR (Time Frame - Every 8-12 weeks until study ends, approximately 4 years):
Proportion of patients with best overall response of CR, PR, or SD

4. DOR (Time Frame - Every 8-12 weeks until study ends, approximately 4 years):
Time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause

5. Time to response (Time Frame - Every 8-12 weeks until study ends, approximately 4 years)

Studien-Arme

  • Experimental: Arm 1
    EGF816+ trametinib in escalation phase
  • Experimental: Arm 2
    EGF816 + ribociclib in escalation phase
  • Experimental: Arm 3
    EGF816 + LXH254 in escalation phase
  • Experimental: Arm A
    EGF816 + INC280 in expansion phase (patients with no known resistance mechanism)
  • Experimental: Arm B
    EGF816 + trametinib in expansion phase
  • Experimental: Arm C
    EGF816 + ribociclib in expansion phase
  • Experimental: Arm D
    EGF816 + LXH254 in expansion phase (patients with no known resistance mechanism)
  • Experimental: Arm E
    EGF816 + LXH254 in expansion phase (patients with known resistance mechanism)
  • Experimental: Arm F
    EGF816 + gefitinib in expansion phase
  • Experimental: Arm G
    EGF816 + INC280 in expansion phase (patients with known resistance mechanism)

Geprüfte Regime

  • EGF816:
    Study Drug
  • trametinib:
    Study Drug
  • ribociclib:
    Study Drug
  • LXH254:
    Study Drug
  • INC280:
    Study Drug
  • gefitinib:
    Study Drug

Quelle: ClinicalTrials.gov


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