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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04985604
Other study ID # DAY101-102
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date July 15, 2021
Est. completion date December 31, 2025

Study information

Verified date March 2024
Source Day One Biopharmaceuticals, Inc.
Contact Day One Biopharmaceuticals
Phone 650-484-0899
Email clinicaltrials@dayonebio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Study DAY101-102 (master study) and sub-studies will consist of a screening period, a treatment period, a safety follow-up period, and a long-term follow-up period where survival, status and subsequent anticancer therapies are collected. Tovorafenib will be evaluated alone or combined with a different targeted therapy in each sub-study. The Phase 1b part of each applicable sub-study will evaluate the safety of the combination and select the dose for the Phase 2 part. The Phase 2 part of each sub-study will evaluate anti-tumor activity. (Closed to Enrollment) Substudy A will enroll patients with recurrent or progressive melanoma or other solid tumors with BRAF fusion or CRAF/RAF1 fusions or amplification. Substudy B will enroll patients with recurrent or progressive melanoma or other solid tumors with alterations in the key proteins of the MAPK pathway.


Recruitment information / eligibility

Status Recruiting
Enrollment 168
Est. completion date December 31, 2025
Est. primary completion date July 31, 2025
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility 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. 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


Intervention

Drug:
Tovorafenib
Tovorafenib tablet for oral use.
Pimasertib
Pimasertib capsule for oral use.

Locations

Country Name City State
Australia Monash Medical Centre Clayton Victoria
Belgium Antwerp University Hospital Edegem
Canada Princess Margaret Cancer Centre Toronto Ontario
Canada The Hospital for Sick Children Toronto Ontario
France Hopital de La Timone - APHM Marseille Bouches-du-Rhône
Korea, Republic of Dong-A University Hospital Busan
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Spain Hospital Clinic Barcelona Barcelona
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Hospital Universitario Ramón y Cajal Madrid
United States University of Colorado Hospital Aurora Colorado
United States Community North Cancer Center Indianapolis Indiana
United States Cancer Specialists of North Florida Jacksonville Florida
United States The Angeles Clinic Los Angeles California
United States Sylvester Comprehensive Cancer Center Miami Florida
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States Hoag Health Newport Beach California
United States UPMC Hillman Cancer Center Pittsburgh Pennsylvania
United States OHSU Knight Cancer Institute Portland Oregon

Sponsors (1)

Lead Sponsor Collaborator
Day One Biopharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Korea, Republic of,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 1b: Determine the safety of tovorafenib in combination with other therapies Incidence and severity of adverse events Up to 48 months
Primary Phase 1b: Determine the MTD and RP2D of tovorafenib in combination with other therapies Incidence and severity of adverse events Up to 48 months
Primary Phase 2: Evaluate the efficacy of tovorafenib monotherapy or in combination with other therapies Overall response rate (ORR) as assessed by the proportion of patients with the best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Up to 48 months
Secondary Phase 1b: Assess efficacy of tovorafenib in combination with other therapies Duration of response (DOR) in patients with best overall response of CR or PR Up to 48 months
Secondary Phase 1b & 2: Assess additional efficacy parameters of tovorafenib alone and in combination with other therapies Duration of progression-free survival (PFS) and overall survival (OS) Up to 48 months
Secondary Phase 1b & 2: Characterize tumor responses observed with tovorafenib alone and in combination with other therapies Time to response (TTR) in patients with best overall response of CR or PR; and comparing the DOR in patients with CR or PR with the DOR observed with the immediate prior line of anticancer treatment Up to 48 months
Secondary Phase 1b & 2: Characterize the pharmacokinetic (PK) profile of tovorafenib alone and in combination with other therapies Measure plasma concentration of tovorafenib Up to 48 months
Secondary Phase 1b & 2: Characterize the pharmacodynamic (PD) profile of tovorafenib alone and in combination with other therapies Evaluate changes from baseline of phosphorylated ERK and other relevant biomarkers Up to 48 months
Secondary Phase 2: Assess the safety and tolerability of tovorafenib as monotherapy, or in combination with other therapies Incidence and severity of adverse events Up to 48 months
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