Phase 1 Safety Study of Encorafenib in Chinese Patients With Advanced Metastatic BRAF V600E Mutant Solid Tumors

NCT05003622 | Completed Phase 1 Results

• 1 other identifier: W00090GE102
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, multicenter, open-label, single-arm study to investigate the safety and tolerability of encorafenib 300 mg once daily (QD) monotherapy in adult Chinese participants with B-RAF Proto-oncogene, Serine/threonine Kinase V600E (BRAF V600E) mutant advanced solid tumors (unresectable metastatic melanoma or metastatic non-small cell lung cancer (NSCLC)), who are BRAF-inhibitor treatment-naïve and have failed the previous therapy(ies) in the metastatic setting or are not eligible to standard therapy. Participants will be eligible for the study based on identification of a BRAF V600E mutation in tumor tissue by a local National Medical Products Administration (NMPA) approved assay obtained prior to screening.

Conditions

BRAF V600E Unresectable or Metastatic Melanoma; BRAF V600E Metastatic NSCLC; Melanoma

Keywords

NSCLC; Melanoma; BRAF V600E mutation

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicities (DLTs) Experienced During Cycle 1

  The primary endpoint was the number of patients experiencing dose limiting toxicity (DLT) occurring within the first 28 days of study treatment (Cycle 1). A DLT was defined as any adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies resulting in the inability to tolerate at least 75% dose intensity \[(administered dose in mg/planned dose in mg) × 100\] that satisfied at least one of the prespecified criteria.

  At the end of Cycle 1. Each cycle was 28 days.

Secondary Outcomes (19)

• Occurrence of Treatment Emergent Adverse Events (TEAEs)

  Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. Each cycle was 28 days.

• Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes.

  Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.

• Notable Change From Baseline of Blood Clinical Chemistry Parameters

  Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.

• Notable Change From Baseline of Coagulation Parameters

  Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle was 28 days.

• Notable Change From Baseline of Dipstick Urinalysis

  Days -28 to -1, Cycle1 Day1 (if not within 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety follow up visit, up to 6 months. Additional urinalysis in Cycle 1 Days 8 and 22. Each cycle was 28 days.

Study Arms (1)

encorafenib

EXPERIMENTAL

Encorafenib hard capsule will be orally self-administered. A fixed-flat dose of 300 mg (4 x 75 mg) Per Oral (PO) encorafenib will be administered once-daily (QD).

Drug: Encorafenib

Interventions

Encorafenib DRUG

oral capsule

Also known as: Braftovi®, PF-07263896, W0090, LGX818, ONO-7702

encorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a signed and dated informed consent form (ICF).
• Chinese male or female with age ≥18 years old at the time of the informed consent.
• Documented histology- and/or cytology-confirmed metastatic melanoma or non-small cell lung cancer (NSCLC) (i.e. adenocarcinoma, large cell carcinoma, squamous cell carcinoma).
• Presence of B-RAF Proto-oncogene, Serine/threonine Kinase V600E Mutant (BRAF V600E) mutation as determined by a local laboratory with a National Medical Products Administration (NMPA) approved BRAF test.
• BRAF inhibitor treatment-naïve participants and having failed the previous therapy(ies) for metastatic disease or are not eligible to standard therapy.
• At least one tumor lesion as per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which has neither been irradiated nor biopsied during the screening period. The irradiated lesion is acceptable only if it is proven as disease progression deemed measurable prior to study.
• Life expectancy ≥3 months.
• Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic function at screening and baseline
• Adequate hepatic function at screening and baseline
• Adequate renal function at screening and baseline
• Able to comply with the study protocol as per investigator assessment including oral drug intake, complying scheduled visits, treatment plan, laboratory tests and other study procedures.
• Women are either postmenopausal for at least 1 year, or are surgically sterile for at least 6 weeks, or women of childbearing potential (WOCBP) must agree to take appropriate precautions to avoid pregnancy.
• Men must agree not to father child until 90 days after the last dose of study treatment.

You may not qualify if:

• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to encorafenib, or its excipients.
• For metastatic NSCLC: documented anaplastic lymphoma kinase (ALK) fusion oncogene, ROS1 (c-ros oncogene 1) rearrangement or epidermal growth factor receptor (EGFR) sensitizing or driver mutation.
• Receipt of anticancer medications or investigational drugs within intervals before the first administration of study treatment.
• Symptomatic brain metastasis.
• Leptomeningeal disease.
• Participant has not recovered to ≤Grade 1 from toxic effects of prior therapy and/or complications from prior surgical treatment before starting study treatment.
• Current use of prohibited medication ≤1 week prior to start of the study treatment and/or concomitantly.
• Impairment of gastrointestinal function or disease which may significantly alter the absorption of oral study treatment.
• Impaired cardiovascular function or clinically significant cardiovascular diseases.
• Participants with active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) or any other severe viral active infection (e.g. severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] infection).
• Evidence of active, non-infectious pneumonitis, history of interstitial lung disease that required oral or intravenous glucocorticoid steroids for management.
• Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Testing for HIV must be performed at sites where mandated locally.
• Participants who have had major surgery (e.g. inpatient procedure with regional or general anesthesia) within 6 weeks prior to start of study treatment.
• Previous or concurrent malignancy within 2 years of study entry.
• Except:

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Melanoma

Interventions

encorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Jean Claude Vedovato
• Organization: Pierre Fabre Medicament

jean.claude.vedovato@pierre-fabre.com

+33 609828746

Study Officials

• Li Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: August 12, 2021
• Study Start: September 27, 2021
• Primary Completion: May 6, 2022
• Study Completion: May 6, 2022
• Last Updated: June 24, 2024
• Results First Posted: June 24, 2024

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)