Tovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors

Day One Biopharmaceuticals

Status and phase

Terminated

Phase 1

Conditions

Solid Tumor

Melanoma

MAP Kinase Family Gene Mutation

Pilocytic Astrocytoma

RAF Mutation

Non Small Cell Lung Cancer

RAS Mutation

MEK Mutation

Pancreatic Cancer

Colorectal Cancer

Treatments

Drug: Tovorafenib Drug: Pimasertib

Drug: Tovorafenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT07121829

DAY101-102b

2021-003768-29 (EudraCT Number)

Details and patient eligibility

About

This is a subprotocol of Master Protocol DAY101-102 and is a Phase 1b/2, multi-center, open label subprotocol of participants ≥12 years of age, with recurrent or progressive solid tumors with alterations in the key proteins of the MAPK pathway, such as tumors that harbor RAS or RAF alterations.

*Note: Study concluded as Phase 1b only.

Enrollment

44 patients

Sex

All

Ages

12+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed informed consent by participant ≥12 years of age; either a Consent or an Assent Form will be provided to the patient based on their capacity, local regulations, and guidelines.
Participants must have a report of histologically confirmed diagnosis of tumor and a concurrent MAPK pathway alteration (genomic alterations in RAS, RAF, MEK, or NF1) obtained 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 regulatory agency
Participants must have radiographically stable, recurrent or progressive disease that is measurable using the appropriate tumor response criteria eg, (RECIST version 1.1, RANO)
Archival tumor tissue should be preferably less than 3 years old. If unavailable, a freshly acquired tumor tissue biopsy or liquid biopsy is required
If brain metastases are present, they must have been previously treated and be stable as assessed by radiographic imaging

Exclusion criteria

Known presence of concurrent activating alterations
Participants with current evidence or a history of serous retinopathy (SR), retinal vein occlusion (RVO) or ophthalmopathy present at screening or baseline who would be considered at risk for SR or RVO
Participants who have an unstable neurological condition, despite adequate treatment (eg, uncontrolled seizures)
Participants with history of acute neurological events (such as intracranial or subarachnoid hemorrhage, stroke, intracranial trauma) within the past 6 months
History of second malignancy within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer, or superficial bladder cancer