Clinical trial NCT05907304: A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations
Official title: An Open-label Study to Assess the Safety and Efficacy of Naporafenib (ERAS-254) Administered With Trametinib in Previously Treated Patients With Locally Advanced Unresectable or Metastatic Solid Tumor Malignancies With RAS Q61X Mutations
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: Melanoma
Non-small cell lung cancer
Thyroid cancer
Colorectal Cancer (cohort full)
Pancreatic Cancer
Other solid tumors harboring a RAS Q61X mutation
Lead sponsor: Erasca, Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-18
Enrollment: 86
Sex: ALL
Minimum age (years): 12
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors

* To evaluate the safety and tolerability of naporafenib administered with trametinib in patients with RAS Q61X solid tumors
* To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when administered to patients with RAS Q61X solid tumors

Detailed description: SEACRAFT-1 is an open-label study to assess the safety and efficacy of naporafenib administered with trametinib in previously treated patients with locally advanced unresectable or metastatic RAS Q61X solid tumor malignancies. The study will enroll a total of approximately 100 adult patients; a sub-study will enroll approximately 15 adolescent patients ≥12 and \<18 years for a total sample size of approximately 115. Patients with a locally advanced unresectable or metastatic solid tumor malignancy that is not responsive to standard therapies or for which there is no standard therapy are eligible. Patients with primary central nervous system (CNS) tumors are not eligible. Documentation of a RAS Q61X mutation in tumor tissue prior to the first dose of study treatment is required.

Eligibility criteria: Key Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Age ≥ 12 years
3. A locally advanced or metastatic tumor who has progressed on or for which no standard therapy exists. Patients who are intolerant to standard therapy or who are not a candidate for standard therapy (in the opinion of the Investigator) or who decline standard therapy are also eligible.
4. Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of study treatment as determined locally with an analytically validated assay in a certified testing laboratory.
5. Archival tumor tissue collected within 5 years prior to enrollment must be confirmed to be available at the time of Screening, which may be submitted before or after enrollment for exploratory biomarker analysis.
6. ECOG performance status 0, 1 or 2
7. Presence of at least 1 measurable lesion according to RECIST v1.1
8. Able to swallow oral medication.

Exclusion Criteria:

1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
2. Impairment of GI function or gastrointestinal (GI) disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
3. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome)
4. Corrected QT interval using Fridericia's formula (QTcF) at Screening \>450 ms based on triplicate average NOTE: criterion does not apply to patients with a right or left bundle branch block
5. LVEF \<50%
6. All primary CNS tumors
7. Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
8. Patients receiving treatment with medications that are known to be strong inhibitors and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A with a narrow therapeutic index and sensitive substrates of CYP3A;
9. Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial

Primary outcomes:
measure: To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
timeFrame: Assessed up to 24 months from time of first dose
Secondary outcomes:
measure: Adverse Events
timeFrame: Assessed up to 24 months from time of first dose
measure: Duration of Response (DOR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Time to Response (TTR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Progression Free Survival (PFS)
timeFrame: Assessed up to 24 months from time of first dose
measure: Disease Control Rate (DCR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Plasma concentration (Cmax)
timeFrame: Study Day 1 up to Day 29
measure: Time to achieve Cmax (Tmax)
timeFrame: Study Day 1 up to Day 29
measure: Area under the curve (AUC)
timeFrame: Study Day 1 up to Day 29
measure: Overall survival
timeFrame: Assessed up to 24 months from time of first dose
Other outcomes:
measure: Duration of Response (DOR) for CNS disease in participants
timeFrame: Assessed up to 24 months from time of first dose
measure: Overall Response Rate (ORR) for CNS disease in participants
timeFrame: Assessed up to 24 months from time of first dose
measure: Disease Control Rate (DCR) for CNS disease in participants
timeFrame: Assessed up to 24 months from time of first dose
measure: Pharmacodynamic assessment
timeFrame: Assessed up to 24 months from time of first dose
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - St. Petersburg
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada (CCCN)
state: Nevada
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: SCRI Oncology Partners (formerly Tennessee Oncology)
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Perth
country: Australia
facility: Linear Clinical Research, LTD
city: Edmonton
country: Canada
facility: Cross Cancer Institute- Alberta Health Services (AHS)
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
state: Busan Gwang'yeogsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Hospital Bundang
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University Hospital
city: City Of London
country: United Kingdom
facility: Sarah Cannon Research Institute - HCA Healthcare
state: London
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Center
Study officials:
affiliation: Clinical Development
name: Joyce Antal, MS
role: STUDY_DIRECTOR
References: