Multicenter, Open-label, Phase 1 Study Investigating the Safety and Tolerability of Encorafenib Monotherapy in BRAF V600E-mutated Chinese Patients With Advanced Metastatic Solid Tumors

Pierre Fabre Medicament1 site in 1 country3 target enrollmentSeptember 27, 2021

ConditionsBRAF V600E Unresectable or Metastatic Melanoma BRAF V600E Metastatic NSCLC Melanoma

InterventionsEncorafenib

Overview

Phase: Phase 1
Intervention: Encorafenib
Conditions: BRAF V600E Unresectable or Metastatic Melanoma
Sponsor: Pierre Fabre Medicament
Enrollment: 3
Locations: 1
Primary Endpoint: Dose Limiting Toxicities (DLTs) Experienced During Cycle 1
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 27, 2021

End Date

May 6, 2022

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Pierre Fabre Medicament

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•Adequate hematologic function at screening and baseline
•Adequate hepatic function at screening and baseline

Exclusion Criteria

•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).

Arms & Interventions

encorafenib

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).

Intervention: Encorafenib

Outcomes

Primary Outcomes

Dose Limiting Toxicities (DLTs) Experienced During Cycle 1

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

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.

Secondary Outcomes

Plasma Pharmacokinetics (PK) of Encorafenib: ARAUC After Single and Repeated Administration of Encorafenib(at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
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 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.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). 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 or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations.(Screening (Days -28 to -1), Cycle 1 Days 1, 8, 15 and 22, Day 1 of each subsequent cycle, the end of treatment visit and the 30-day safety follow-up visit, approximately up to 6 months. Each cycle was 28 days.)
Occurrence of Targeted Treatment Emergent Adverse Events (TEAEs) of Special Interest(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.)
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 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.)
Plasma Pharmacokinetics (PK) of Encorafenib: Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib: Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib: Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs)(Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle, and the end of treatment visit, approximately up to 6 months. Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): ARAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)(First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.)