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JOURNAL ONKOLOGIE – STUDIE
FIREFLY-1

A Study to Evaluate DAY101 in Pediatric and Young Adult Patients With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors

Rekrutierend

NCT-Nummer:
NCT04775485

Studienbeginn:
April 2021

Letztes Update:
27.12.2023

Wirkstoff:
DAY101

Indikation (Clinical Trials):
Glioma

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
Phase 2

Sponsor:
Day One Biopharmaceuticals, Inc.

Collaborator:
Pacific Pediatric Neuro-Oncology Consortium

Kontakt

Studienlocations
(3 von 35)

Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Otto-Heubner-Centrum für Kinder
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Hopp-Kindertumorzentrum Heidelberg (KiTZ), KiTZ Clinical Trial Unit (ZIPO)
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
UCSF Benioff Children's Hospital
94143 San Francisco
United StatesRekrutierend» Google-Maps
Lurie Children's Hospital of Chicago
60611 Chicago
United StatesRekrutierend» Google-Maps
Johns Hopkins Hospital
21231 Baltimore
United StatesAbgebrochen» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
CS Mott Children's Hospital
48109 Ann Arbor
United StatesRekrutierend» Google-Maps
St. Louis Children's Hospital
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Doernbecher Children's Hospital Oregon & Health Science University
97239 Portland
United StatesAbgebrochen» Google-Maps
Children's Hospital of Philadelphia
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Texas Children's Hospital
77030 Houston
United StatesRekrutierend» Google-Maps
University of Utah
84113 Salt Lake City
United StatesRekrutierend» Google-Maps
Seattle Children's Hospital
98105 Seattle
United StatesRekrutierend» Google-Maps
Queensland Children's Hospital
4101 Brisbane
AustraliaRekrutierend» Google-Maps
Royal Children's Hospital
3052 Parkville
AustraliaRekrutierend» Google-Maps
Sydney Children's Hospital
NSW 2031 Randwick
AustraliaRekrutierend» Google-Maps
The Children's Hospital at Westmead
2145 Westmead
AustraliaRekrutierend» Google-Maps
Centre Hospitalier Universitaire Ste-Justine
H3T 1C5 Montreal
CanadaRekrutierend» Google-Maps
Montreal Children's Hospital
H4A 3J1 Montreal
CanadaRekrutierend» Google-Maps
Centre Mère-Enfant Soleil du CHU
G1V 4G2 Québec
CanadaRekrutierend» Google-Maps
Schneider Children's Medical Center of Israel
4920235 Petah Tikva
IsraelRekrutierend» Google-Maps
The Chaim Sheba Medical Center
5265601 Ramat Gan
IsraelRekrutierend» Google-Maps
Seoul National University Hospital
3080 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Severance Hospital - Yonsei University
3722 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Princess Maxima Center for Pediatric Oncology
3584 CS Utrecht
NetherlandsRekrutierend» Google-Maps
KK Women's and Children's Hospital
229899 Singapore
SingaporeRekrutierend» Google-Maps
Universitäts-Kinderspital Zürich - Eleonorenstiftung
8032 Zürich
SwitzerlandRekrutierend» Google-Maps
UCL Great Ormond Street Institute of Child Health
WC1N 1EH London
United KingdomRekrutierend» Google-Maps
Newcastle University
NE1 7RU Newcastle Upon Tyne
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The study will consist of the following treatment arms:

Arm 1 (Low-Grade Glioma): Patients aged 6 months to 25 years, inclusive, with recurrent or

progressive low-grade glioma harboring a known activating BRAF alteration, including BRAF

V600 mutations and KIAA1549:BRAF fusions.

Arm 2 (Low-Grade Glioma Expanded Access): Patients aged 6 months to 25 years, inclusive, with

recurrent or progressive low-grade glioma harboring a known or expected to be activating RAF

alteration (e.g., BRAF or CRAF/RAF1 fusion or BRAF V600 mutations). Opening of Arm 2 to

enrollment will be based on the recommendation of the Data Safety Monitoring Board (DSMB).

Arm 3 (Advanced Solid Tumor): Patients aged 6 months to 25 years, inclusive, with advanced

solid tumors harboring a known or expected to be activating RAF fusion (e.g., BRAF or

CRAF/RAF1 fusion).

Qualifying genomic alterations will be identified through molecular assays as routinely

performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly

certified laboratories prior to enrollment into any of the aforementioned arms.

Patients will be treated with DAY101, an oral pan-RAF inhibitor, for a planned period of 26

cycles will be treated with DAY101 for a planned period of 26 cycles (approximately 24

months).

DAY101 will be administered at the recommended Phase 2 dose (RP2D) of 420 mg/m2 (not to

exceed 600 mg) orally once weekly (QW) for each 28-day treatment cycle.

Treatment cycles will repeat every 28 days in the absence of disease progression or

unacceptable toxicity. Patients will undergo radiographic evaluation of their disease at the

end of every third cycle. Patients will continue on DAY101 until radiographic evidence of

disease progression by RANO (Arms 1 & 2) or RECIST v1.1 criteria (Arm 3) as determined by

treating investigator, unacceptable toxicity, patient withdrawal of consent, or death.

Patients who have radiographic evidence of disease progression may be allowed to continue

DAY101 if, in the opinion of the investigator and approval by the Sponsor, the patient is

deriving clinical benefit from continuing study treatment. Disease assessments for patients

being treated beyond progression should continue as per regular schedule.

DAY101 is an oral pan-RAF inhibitor administered as an oral tablet at 420 mg/m2 (not to

exceed 600 mg).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Age 6 months to 25 years with:

1. Arms 1 & 2: a relapsed or progressive LGG with documented known activating BRAF

alteration

2. Arm 3: locally advanced or metastatic solid tumor with documented known or

expected to be activating RAF fusion

- Confirmation of histopathologic diagnosis of LGG and molecular diagnosis of activating

BRAF alteration

- Must have received at least one line of systemic therapy and have evidence of

radiographic progression

- Must have at least 1 measurable lesion as defined by RANO (Arms 1 & 2) or RECIST v1.1

(Arm 3) criteria

Exclusion Criteria:

- Patient's tumor has additional previously-known activating molecular alterations

- Patient has symptoms of clinical progression in the absence of radiographic

progression

- Known or suspected diagnosis of neurofibromatosis type 1 (NF-1)

- Other inclusion/exclusion criteria as stipulated by protocol may apply

Studien-Rationale

Primary outcome:

1. Arm 1: Overall response rate (ORR) by independent radiology review committee (IRC) based on RANO criteria (Time Frame - Up to 48 months):
ORR defined as the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by RANO criteria

2. Arm 2: Assess the safety and tolerability of DAY101 (Time Frame - Up to 48 months):
Type, frequency, and severity of treatment-emergent adverse events and laboratory

3. Arm 3: Overall response rate (ORR) by independent radiology review committee (IRC) based on RECIST v1.1 criteria (Time Frame - Up to 48 months):
Measured by the proportion of patients with best overall confirmed response of CR or PR by RECIST v1.1 criteria

Secondary outcome:

1. Relationship between pharmacokinetics (PK) and drug effects (Time Frame - Up to 48 months):
Pharmacokinetic profile of DAY101 (e.g., area under the concentration-time curve [AUC], Cmin, etc.)

2. Effect on electrocardiogram (ECG) and QT interval corrected for heart rate by Fridericia's formula (QTcF) prolongation (Time Frame - Up to 48 months):
Change from baseline QT interval corrected for HR by Fridericia's formula (ΔQTcF); change from baseline PR interval (ΔPR); change from baseline QRS interval (ΔQRS); change from baseline heart rate (ΔHR); ECG waveform morphology

3. ORR by Investigator (Time Frame - Up to 48 months):
Measured by the proportion of patients with best overall confirmed response of CR or PR by RANO (Arms 1 & 2) or RECIST (Arm 3) criteria

4. Evaluate the concordance of prior local laboratory BRAF molecular profiling with a central BRAF alteration assay being evaluated by the Sponsor (Time Frame - Up to 48 months):
Molecular analysis of cells obtained from archival tissue

5. Arm 1: Evaluate visual acuity (VA) outcomes compared with baseline (Time Frame - Up to 48 months):
Measured by Teller Acuity Cards® II

6. Arms 1 & 2: ORR by IRC and Investigator using RAPNO criteria (Time Frame - Up to 48 months):
Measured by the proportion of patients with best overall confirmed response of CR or PR by RAPNO-LGG criteria

7. Arms 1 & 2: Progression free survival (PFS) using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only) (Time Frame - Up to 48 months):
Measured by the time following initiation of DAY101 to progression or death in patients treated with DAY101

8. Arms 1 & 2: Duration of response (DOR) with best overall response of CR or PR using RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only) (Time Frame - Up to 48 months):
Measured by the length of response in patients with best overall confirmed response of CR or PR by RANO and RAPNO criteria

9. Arms 1 & 2: Time to response following initiation of DAY101 (Time Frame - Up to 48 months):
Measured by the time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR by RANO and RAPNO criteria by 1) an IRC and 2) the treating Investigator (RANO only)

10. Arms 1 & 2: Clinical benefit rate based on the proportion of patients with best overall response using RANO or RAPNO criteria (Time Frame - Up to 48 months):
Measured on the proportion of patients with best overall response of CR, PR, or SD lasting 12 months or more following initiation of DAY101 by 1) an IRC and 2) the treating Investigator (RANO only)

11. Arms 1 & 3: Assess the safety and tolerability of DAY101 (Time Frame - Up to 48 months):
Type, frequency, and severity of treatment-emergent adverse events and laboratory abnormalities

12. Arm 3: Duration of response (DOR) with best overall response of CR or PR using RECIST v1.1 criteria by 1) an IRC and 2) the treating Investigator (Time Frame - Up to 48 months):
Measured by the length of response in patients with best overall confirmed response of CR or PR by RECIST v1.1 criteria

13. Arm 3: Time to response following initiation of DAY101 (Time Frame - Up to 48 months):
Measured by the time to first response following initiation of DAY101 in patients with best overall confirmed response of CR or PR by RECIST v1.1 criteria by 1) an IRC and 2) the treating Investigator

14. Arm 3: Clinical benefit rate based on the proportion of patients with best overall response using RECIST v1.1 criteria (Time Frame - Up to 48 months):
Measured on the proportion of patients with best overall response of CR, PR, or SD lasting 12 months or more following initiation of DAY101 by 1) an IRC and 2) the treating Investigator

Studien-Arme

  • Experimental: Arm #1
    Pediatric patients with low-grade glioma treated with DAY101 (Registrational Arm)
  • Experimental: Arm #2
    Expanded access arm of pediatric patients with low-grade glioma treated with DAY101
  • Experimental: Arm #3
    Pediatric patients with advanced solid tumors treated with DAY101

Geprüfte Regime

  • DAY101:
    DAY101 is an oral pan-RAF inhibitor provided as an immediate-release tablet (100 mg) or powder for reconstitution (25 mg/mL).

Quelle: ClinicalTrials.gov


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