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| Name | Class |
|---|---|
| Pacific Pediatric Neuro-Oncology Consortium | OTHER |
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This is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of Type II RAF (tovorafenib) in pediatric participants with low-grade glioma or advanced solid tumors. 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 arms. The study will consist of a screening period, a treatment period, a long-term extension phase, end of treatment (EOT) visit(s), a safety follow-up visit, and long-term follow-up assessments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Low-Grade Glioma | Experimental | Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA). |
|
| Arm 2: Low-Grade Glioma Expanded Access | Experimental | Participants with recurrent or progressive low-grade glioma will receive 420 mg/m^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA. |
|
| Arm 3: Advanced Solid Tumor | Experimental | Participants with advanced solid tumors will receive 420 mg/m^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tovorafenib | Drug | Tovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Arm 1: Overall response rate | ORR is defined as percentage of participants with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) criteria. | Up to 48 months |
| Arm 2: Number of participants reporting adverse events | An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 48 months |
| Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters | Up to 48 months | |
| Arm 2: Number of participants with clinically significant changes in hematology parameters | Up to 48 months | |
| Arm 3: Overall response rate | Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate. | Up to 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Arm 1 and 3: Number of participants reporting adverse events | An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Up to 48 months |
| Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters |
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Inclusion Criteria:
Exclusion Criteria:
Other inclusion/exclusion criteria as stipulated by protocol may apply
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Day One Biopharmaceuticals, Inc. | Contact | 650-484-0899 | firefly-1@dayonebio.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital | Recruiting | San Francisco | California | 94143 | United States | |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37978284 | Derived | Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024 Jan;30(1):207-217. doi: 10.1038/s41591-023-02668-y. Epub 2023 Nov 17. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 21, 2021 | May 9, 2024 |
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|
| Up to 48 months |
| Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters | Up to 48 months |
| Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib | Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1 |
| Arm 1: Minimum drug concentration (Cmin) | Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1 |
| Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (ΔQTcF) | Baseline to 48 months |
| Arm 1: Change from Baseline PR interval (ΔPR) | Baseline to 48 months |
| Arm 1: Change from Baseline QRS interval (ΔQRS) | Baseline to 48 months |
| Arm 1: Change from baseline heart rate (ΔHR) | Baseline to 48 months |
| Arm 1: Change in electrocardiogram (ECG) waveform morphology | Baseline to 48 months |
| Arm 1 and Arm 2: Overall response rate | ORR is defined as percentage of participants with best overall confirmed response of CR or PR by the RANO-HGG criteria. | Up to 48 months |
| Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants | ORR is defined as percentage of participants with best overall confirmed response of CR or PR or minor response (MR) by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.CR or PR by RECIST v1.1 criteria. | Up to 48 months |
| Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS) | PFS as defined by the time following initiation of tovorafenib to progression or death in participants treated with tovorafenib measured by RECIST v1.1, RAPNO, or RANO-HGG criteria as determined by the treating investigator and an IRC. | Up to 48 months |
| Arm 1, Arm 2 and Arm 3: Duration of response (DOR) | DOR as defined by the length of response in participants with best overall confirmed response of CR or PR or MR and measured by RANO-HGG, RAPNO, and/or RECIST v1.1 criteria, as applicable. | Up to 48 months |
| Arm 1, Arm 2 and Arm 3: Time to response (TTR) | TTR as defined as the time to first response following initiation of tovorafenib in participants with best overall confirmed response of CR or PR measured by RECIST v1.1 or RANO-HGG criteria, as applicable. | Up to 48 months |
| Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR) | CBR as defined as participants with BOR of CR, PR or stable disease (SD) measured by RECIST v1.1 or RANO-HGG, as applicable, and lasting 12 months or more following initiation of tovorafenib. | Up to 48 months |
| Arm 1 and Arm 2: Duration of overall survival | Overall survival as defined by the time following initiation of tovorafenib to death of any cause in participants treated with tovorafenib. | Up to 48 months |
| Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes | Baseline to 48 months |
| Arm 1: Changes in molecular analysis of cells obtained from archival tissue | At Screening |
| Children's National Medical Center |
| Recruiting |
| Washington D.C. |
| District of Columbia |
| 20010 |
| United States |
|
| Lurie Children's Hospital of Chicago | Recruiting | Chicago | Illinois | 60611 | United States |
| Johns Hopkins Hospital | Terminated | Baltimore | Maryland | 21231 | United States |
| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
| CS Mott Children's Hospital | Recruiting | Ann Arbor | Michigan | 48109 | United States |
| St. Louis Children's Hospital | Recruiting | St Louis | Missouri | 63110 | United States |
| NYU Langone Health | Recruiting | New York | New York | 10016 | United States |
| Duke Cancer Center | Recruiting | Durham | North Carolina | 27710 | United States |
| Doernbecher Children's Hospital Oregon & Health Science University | Terminated | Portland | Oregon | 97239 | United States |
| Children's Hospital of Philadelphia | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
| Texas Children's Hospital | Recruiting | Houston | Texas | 77030 | United States |
| University of Utah | Recruiting | Salt Lake City | Utah | 84113 | United States |
| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98105 | United States |
| Queensland Children's Hospital | Recruiting | Brisbane | 4101 | Australia |
| Royal Children's Hospital | Recruiting | Parkville | 3052 | Australia |
| Perth Children's Hospital | Recruiting | Perth | WA 6009 | Australia |
| Sydney Children's Hospital | Recruiting | Randwick | NSW 2031 | Australia |
| The Children's Hospital at Westmead | Recruiting | Westmead | 2145 | Australia |
| Centre Hospitalier Universitaire Ste-Justine | Recruiting | Montreal | Quebec | H3T 1C5 | Canada |
| Montreal Children's Hospital | Recruiting | Montreal | Quebec | H4A 3J1 | Canada |
| Centre Mère-Enfant Soleil du CHU | Recruiting | Québec | Quebec | G1V 4G2 | Canada |
| Rigshospitalet | Recruiting | Copenhagen | Denmark |
| Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Otto-Heubner-Centrum für Kinder | Recruiting | Berlin | 13353 | Germany |
| Hopp-Kindertumorzentrum Heidelberg (KiTZ), KiTZ Clinical Trial Unit (ZIPO) | Recruiting | Heidelberg | 69120 | Germany |
| Rambam Health Care Campus | Recruiting | Haifa | 3109601 | Israel |
| Schneider Children's Medical Center of Israel | Recruiting | Petah Tikva | 4920235 | Israel |
| The Chaim Sheba Medical Center | Recruiting | Ramat Gan | 5265601 | Israel |
| Princess Maxima Center for Pediatric Oncology | Recruiting | Utrecht | 3584 CS | Netherlands |
| KK Women's and Children's Hospital | Recruiting | Singapore | 229899 | Singapore |
| Seoul National University Hospital | Recruiting | Seoul | 3080 | South Korea |
| Severance Hospital - Yonsei University | Recruiting | Seoul | 3722 | South Korea |
| Universitäts-Kinderspital Zürich - Eleonorenstiftung | Recruiting | Zurich | 8032 | Switzerland |
| UCL Great Ormond Street Institute of Child Health | Recruiting | London | WC1N 1EH | United Kingdom |
| Newcastle University | Recruiting | Newcastle upon Tyne | NE1 7RU | United Kingdom |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 5, 2023 | May 8, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000626518 | tovorafenib |
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