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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04985604




Registration number
NCT04985604
Ethics application status
Date submitted
23/06/2021
Date registered
2/08/2021
Date last updated
29/03/2024

Titles & IDs
Public title
Tovorafenib (DAY101) Monotherapy or in Combination With Other Therapies for Patients With Melanoma and Other Solid Tumors
Scientific title
A Phase 1b/2, Open Label Study of DAY101 Monotherapy or Combination With Other Therapies for Patients With Recurrent, Progressive, or Refractory Solid Tumors Harboring MAPK Pathway Aberrations
Secondary ID [1] 0 0
DAY101-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Solid Tumor 0 0
CRAF Gene Amplification 0 0
RAF1 Gene Amplification 0 0
BRAF Gene Fusion 0 0
BRAF Fusion 0 0
CRAF Gene Fusion 0 0
CRAF Fusion 0 0
RAF1 Gene Fusion 0 0
RAF1 Fusion 0 0
Thyroid Cancer, Papillary 0 0
Spitzoid Melanoma 0 0
Pilocytic Astrocytoma 0 0
Pilocytic Astrocytoma, Adult 0 0
Non Small Cell Lung Cancer 0 0
Non-Small Cell Adenocarcinoma 0 0
Colorectal Cancer 0 0
Pancreatic Acinar Carcinoma 0 0
Spitzoid Malignant Melanoma 0 0
Bladder Cancer 0 0
Bladder Urothelial Carcinoma 0 0
MAP Kinase Family Gene Mutation 0 0
RAS Mutation 0 0
RAF Mutation 0 0
MEK Mutation 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tovorafenib
Treatment: Drugs - Pimasertib

Experimental: Arm #1 (Closed to Enrollment) - Tovorafenib monotherapy

Experimental: Arm #2 - Tovorafenib plus pimasertib


Treatment: Drugs: Tovorafenib
Tovorafenib tablet for oral use.

Treatment: Drugs: Pimasertib
Pimasertib capsule for oral use.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Determine the safety of tovorafenib in combination with other therapies
Timepoint [1] 0 0
Up to 48 months
Primary outcome [2] 0 0
Phase 1b: Determine the MTD and RP2D of tovorafenib in combination with other therapies
Timepoint [2] 0 0
Up to 48 months
Primary outcome [3] 0 0
Phase 2: Evaluate the efficacy of tovorafenib monotherapy or in combination with other therapies
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [1] 0 0
Phase 1b: Assess efficacy of tovorafenib in combination with other therapies
Timepoint [1] 0 0
Up to 48 months
Secondary outcome [2] 0 0
Phase 1b & 2: Assess additional efficacy parameters of tovorafenib alone and in combination with other therapies
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Phase 1b & 2: Characterize tumor responses observed with tovorafenib alone and in combination with other therapies
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [4] 0 0
Phase 1b & 2: Characterize the pharmacokinetic (PK) profile of tovorafenib alone and in combination with other therapies
Timepoint [4] 0 0
Up to 48 months
Secondary outcome [5] 0 0
Phase 1b & 2: Characterize the pharmacodynamic (PD) profile of tovorafenib alone and in combination with other therapies
Timepoint [5] 0 0
Up to 48 months
Secondary outcome [6] 0 0
Phase 2: Assess the safety and tolerability of tovorafenib as monotherapy, or in combination with other therapies
Timepoint [6] 0 0
Up to 48 months

Eligibility
Key inclusion criteria
- Signed informed consent by patients = 18 years of age and, assent for patients = 12 up
to < 18 years of age

- Patients must have radiographically-recurrent or radiographically-progressive disease
that is measurable using the appropriate tumor response criteria (e.g. RECIST version
1.1)

- Archival tumor tissue (preferably less than 3 years old) or fresh tumor tissue for
correlative studies is required

- If brain metastases are present, they must have been previously treated and be stable
as assessed by radiographic imaging

(Closed to Enrollment) Substudy A-specific inclusion criterion:

- Patients must have a report of histologically confirmed diagnosis of melanoma or other
solid tumor and a concurrent BRAF fusion, CRAF/RAF1 fusion, or CRAF/RAF1 amplification
through a tumor or liquid biopsy as assessed by genomic sequencing, polymerase chain
reaction (PCR), fluorescence in situ hybridization (FISH), or another clinically
accepted molecular diagnostic method recognized by local laboratory or agency.

Substudy B-specific inclusion criterion:

- Patients must have a report of histologically confirmed diagnosis of melanoma or other
solid tumor and a concurrent MAPK pathway alteration (genomic alterations in RAS, RAF,
MEK, or NF1) through a tumor or liquid biopsy as assessed by genomic sequencing, PCR,
FISH, or another clinically accepted molecular diagnostic method recognized by local
laboratory or agency.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known presence of concurrent activating mutation

- Patients with current evidence or a history of central serous retinopathy (CSR),
retinal vein occlusion (RVO)

(Closed to Enrollment) Substudy A-specific exclusion criterion:

- Prior therapy of any RAS- RAF-, MEK-, or ERK-directed inhibitor therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
168
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
Belgium
State/province [8] 0 0
Edegem
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
France
State/province [10] 0 0
Bouches-du-Rhône
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Busan
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Day One Biopharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b/2, multi-center, open label umbrella study of patients =12 years of age
with recurrent, progressive, or refractory melanoma or other solid tumors with alterations in
the key proteins of the RAS/RAF/MEK/ERK pathway, referred to as the MAPK pathway.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04985604
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Day One Biopharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
650-484-0899
Fax 0 0
Email 0 0
clinicaltrials@dayonebio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04985604