Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

Official title

A Multicenter, Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

Overview

This is a multicenter, randomized, open-label, Phase 3 study

Detailed description

This is a multicenter, randomized, open-label, Phase 3 study to evaluate Tunlamatinib plus Vemurafenib versus Investigator's choice of Chemotherapy based treatment as controls in patients with BRAFV600E mutant Metastatic Colorectal Cancer (CRC) whose disease has progressed after 1 or more prior regimens in the metastatic setting.

Interventions

• Drug Tunlametinib plus Vemurafenib
  12mg BID Tunlametinib+720mg BID Vemurafenib
• Drug Doublets Chemotherapy ± Bevacizumab or Doublets Chemotherapy ± Cetuximab
  According to investigators' suggestion

Primary outcome measures

• Progression-free Survival (PFS) [Time frame: up to 12 months]

Secondary outcome measures (4)

• Overall Survival（OS） [Time frame: up to 12 months]
• Overall Response Rate（ORR） [Time frame: up to 12 months]
• Duration of Response（DOR） [Time frame: up to 12 months]
• Disease control rate (DCR) [Time frame: up to 12 months]

Eligibility criteria

Inclusion criteria

• Inclusion Criteria:

• Before study entry, written informed consent must be obtained from the patient prior to performing any study-related procedures.
• Male or female patients with 18 to 70 years of age at time of informed consent;
• Histological or cytologically confirmed metastatic CRC
• Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory (BRAFV600 is permitted)
• Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archival or newly obtained) for confirmatory central laboratory testing of BRAF mutation status.
• Progression of disease after 1 or more prior regimens in the metastatic setting
• At least 1 site of radiographically measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) of 0 to 1;
• Life expectancy ≥ 3 months;
• Can swallow the medicine,
• Adequate hematologic, renal, cardiac and liver function as defined by laboratory values performed within 7 days prior to initiation of dosing:
• Be willing and able to complete all the study procedures and follow-up examinations.

Exclusion criteria

• Exclusion Criteria:

• Prior treatment with any BRAF and MEK inhibitor;
• Known contraindication to receive the treatment of control arm (according to latest PI).
• Symptomatic brain metastasis or leptomeningeal disease
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
• Known history of acute or chronic pancreatitis
• Uncontrolled GI bleeding, Dysphagia，refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
• Serious cardiovascular disease , including uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia , deep vein thrombosis or pulmonary emboli or cerebrovascular events ≤ 6 months prior to starting study treatment;
• History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Uncontrolled blood pressure despite medical treatment
• Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
• Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy
• Anti-HIV(+) , Anti-TP( +); Active hepatitis B or hepatitis C infection …….

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Oncology Hospital — Beijing

Identifiers

NCT: NCT06008119 · HL-085-304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗