Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung Cancer

NCT05195632 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: W00090GE203CTR20212962CTR20212961
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 34

Brief Summary

This is a phase 2, multicenter, single-arm study with a safety lead-in to investigate the efficacy, safety and pharmacokinetics of encorafenib 450 mg once daily (QD) in combination with binimetinib 45 mg twice daily (BID) (Combo450) in adult Chinese participants with metastatic unresectable stage IV BRAF V600E mutant NSCLC, who are BRAF- and MEK-inhibitor treatment-naïve and are either previously untreated or have had one line of prior therapy in metastatic setting.

Conditions

Non-Small Cell Lung Cancer

Keywords

Encorafenib; Binimetinib; Lung Cancer; BRAF-inhibitor; MEK-inhibitor; BRAF V600E -mutated Chinese patients; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety Lead-In (SLI) Part: Incidence of Dose-limiting toxicities (DLTs)

  Incidence of DLTs experienced during the Cycle 1 (days 1 to 28) after the first dose of study treatment. DLT rate defined as the number of DLT-evaluable participants with DLTs in the first 28 days after first dose of study treatment in the SLI (DLT-evaluation period), divided by the number of DLT-evaluable participants.

  Cycle 1; Each cycle is 28 days

• Pivotal Part: Confirmed objective response rate (cORR)

  cORR defined as the percentage of participants who have achieved a complete response (CR) or partial response (PR) as determined by Independent Central Review (ICR) of radiographic disease assessments according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Proportion of patients who have achieved a confirmed Best Overall Response (cBOR) of CR or PR as determined by per RECIST v1.1 and corresponding exact two-sided binomial 95% Confidence interval (CI).

  Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after EOT visit/last dose if EOT not performed), approximately up to 18 months. Each cycle is 28 days.

Secondary Outcomes (51)

• Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Area under the curve (AUC)

  Cycle 1 Day 1; Each cycle is 28 days

• Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Minimum serum concentration (Cmin)

  Cycle 1 Day 1; Each cycle is 28 days

• Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of encorafenib: Maximum serum concentration (Cmax)

  Cycle 1 Day 1; Each cycle is 28 days

• Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib: Area under the curve (AUC)

  Cycle 1 Day 1; Each cycle is 28 days

• Safety Lead-In (SLI) Part: Pharmacokinetic (PK) parameter of binimetinib: Minimum serum concentration (Cmin)

  Cycle 1 Day 1; Each cycle is 28 days

Study Arms (1)

Treatment arm (Safety Lead-in and Pivotal arm)

EXPERIMENTAL

Encorafenib will be administered as a fixed, flat oral dose of 450 mg QD in combination with binimetinib as a fixed, flat oral dose of 45 mg BID.

Drug: Encorafenib; Drug: Binimetinib

Interventions

Encorafenib DRUG

Hard capsule

Also known as: PF-07263896 or W0090 (in Europe), LGX818 (in US), ONO-7702 (in Japan)

Treatment arm (Safety Lead-in and Pivotal arm)

Binimetinib DRUG

Film-coated tablet

Also known as: W0074 (in Europe), MEK162 (in US), ARRY-438162 (in US), ONO-7703 (in Japan)

Treatment arm (Safety Lead-in and Pivotal arm)

Eligibility Criteria

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

You may qualify if:

• If a participant has a BRAF V600E mutational status confirmed as per local assessment, the participant might enter the main screening directly.
• Provide a signed and dated screening Informed Consent Form (ICF).
• Chinese male or female with age ≥ 18 years old for China mainland and ≥ 20 years old for Taiwan at the time of the screening informed consent.
• Documented histology- and/or cytology-confirmed metastatic unresectable Non-small cell lung cancer (NSCLC (i.e. Adenocarcinoma (ADC), large cell carcinoma, squamous cell carcinoma (SCC)).
• Presence of B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600E mutation in tumor tissue previously determined by a local assay at any time prior to screening or by the central laboratory.
• Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archived or newly obtained) for central prospective laboratory testing of BRAF mutation status and comparison of central BRAF V600E testing in the clinical study to BRAF V600E testing with a candidate companion diagnostic.
• BRAF- and Mitogen-activated protein kinase kinase (MEK)-inhibitor treatment-naïve participants and previously untreated or have had one line of prior therapy in metastatic setting.
• At least one measurable disease as per investigator assessment, as defined by RECIST v1.1, which has neither been irradiated nor biopsied during the screening period.
• Life expectancy ≥ 3 months.
• Eastern Cooperative 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, are surgically sterile for at least 6 weeks, or child-bearing potential women must agree to take appropriate precautions to avoid pregnancy.

You may not qualify if:

• Participants meeting any of the following criteria are not eligible to be included in this study:
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs (encorafenib and binimetinib), or their excipients.
• Documented Anaplastic lymphoma kinase (ALK) fusion oncogene, Reactive oxygen species (ROS) rearrangement or Epidermal growth factor receptor (EGFR) sensitizing or driver mutation.
• Participants who have received more than one prior line of systemic therapy.
• Receipt of anti-cancer medications or investigational drugs within the specified intervals before the first administration of study treatment.
• Symptomatic brain metastases or other active Central nervous system (CNS) metastases.
• Leptomeningeal disease.
• Participant has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention 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
• History of thromboembolic or cerebrovascular events within 3 months prior to starting the study treatments
• History or evidence of retinal pathology considered as risk factor for Retinal vein occlusion (RVO) or neovascular macular degeneration.
• Concurrent neuromuscular disorder associated with the potential of elevated Creatine phosphokinase (CPK)
• Participants with active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or any other severe viral active infection (e.g. SARS-CoV-2 infection)

Sponsors & Collaborators

• Pierre Fabre Medicament: lead

Study Sites (34)

Beijing Cancer Hospital

Beijing, China

Location

Beijing Chest Hospital, Capital Medical University

Beijing, China

Location

Peking University First Hospital

Beijing, China

Location

The First Hospital of Jilin University

Changchun, China

Location

Xiangya Hospital Central South University

Changsha, China

Location

Sichuan Cancer Hospital

Chengdu, China

Location

Chongqing University Cancer Hospital

Chongqing, China

Location

The Second Hospital of Dalian University

Dalian, China

Location

Fujian Medical University Union Hospital

Fuzhou, China

Location

Fuzhou Tuberculosis Prevention and Control Hospital of Fujian Province (Fuzhou Pulmonary Hospital of Fujian)

Fuzhou, China

Location

Guangdong Provincial People's Hospital

Guangzhou, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, China

Location

Hainan General Hospital

Haikou, China

Location

First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China

Location

Zhejiang Cancer Hospital

Hangzhou, China

Location

Zhejiang University School of Medicine, Sir Run Run Shaw Hospital

Hangzhou, China

Location

Harbin Medical University Cancer Hospital

Harbin, China

Location

Shandong Cancer Hospital

Jinan, China

Location

The First Affiliated Hospital of Jinzhou Medical University

Jinzhou, China

Location

Linyi Cancer Hospital

Linyi, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, China

Location

Guangxi Medical University Affiliated Tumor Hospital

Nanning, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, China

Location

The First Hospital of China Medical University

Shenyang, China

Location

Peking University Shenzhen Hospital

Shenzhen, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, China

Location

Shanxi Provincial Cancer Hospital

Taiyuan, China

Location

Tianjin Cancer Hospital Airport Hospital

Tianjin, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, China

Location

Union Hospital Tongji medical college Huazhong University of Science and Technology

Wuhan, China

Location

The Northern Jiangsu People's Hospital

Yangzhou, China

Location

Yantai Yuhuangding Hospital

Yantai, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

encorafenib; binimetinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, MD

  Sun Yat-sen Univ. Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label, phase 2 study.

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 19, 2022
• Study Start: June 2, 2022
• Primary Completion: May 27, 2024
• Study Completion (Estimated): December 14, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1); CN (33)