HSK42360-Na Tablets Combined With Cetuximab With or Without Chemotherapy in BRAF V600-Mutant Metastatic Colorectal Cancer

NCT07790510 | Recruiting Phase 1 DMC

• 1 other identifier: HSK42360-Na-T1-201
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II, single-arm, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HSK42360-Na tablets combined with cetuximab with or without chemotherapy in patients with BRAF V600-mutant metastatic colorectal cancer (mCRC). The Phase I stage uses a 3+3 dose escalation design to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of HSK42360-Na in combination with cetuximab. The Phase II stage evaluates the efficacy and safety of HSK42360-Na combined with cetuximab alone or with mFOLFOX6/FOLFIRI chemotherapy in expansion cohorts.

Conditions

Metastatic Colorectal Cancer (CRC)

Outcome Measures

Primary Outcomes (3)

• dose-limiting toxicities (DLTs)

  Incidence and severity of dose-limiting toxicities (DLTs) during the first 28-day treatment cycle.

  during the first 28-day treatment cycle.

• Maximum tolerated dose (MTD)

  Up to approximately 8 months

• recommended Phase II dose (RP2D)

  Up to approximately 8 months

Secondary Outcomes (10)

• Tmax

  Up to approximately 36 months

• Objective response rate (ORR)

  Up to approximately 36 months

• Progression-free survival (PFS)

  Up to approximately 36 months

• Overall survival (OS)

  Up to approximately 36 months

• Duration of response (DOR)

  Up to approximately 36 months

Other Outcomes (1)

• Changes in circulating tumor DNA (ctDNA) levels from baseline.

  Up to approximately 36 months

Study Arms (2)

Phase I Dose Escalation

EXPERIMENTAL

Drug: HSK42360-Na Tablets; Drug: Cetuximab (EGFR inhibitor)

Phase II Cohort Expansion

EXPERIMENTAL

Drug: HSK42360-Na Tablets; Drug: Cetuximab (EGFR inhibitor); Drug: mFOLFOX6 Regimen (Oxaliplatin/Leucovorin/5-FU); Drug: FOLFIRI Regimen (Irinotecan/Leucovorin/5-FU)

Interventions

HSK42360-Na Tablets DRUG

HSK42360-Na tablets administered orally once, twice, or three times daily depending on the assigned dose level, in 28-day treatment cycles.

Phase I Dose Escalation; Phase II Cohort Expansion

Cetuximab (EGFR inhibitor) DRUG

Cetuximab 500 mg/m2 administered by intravenous infusion every 2 weeks.

Phase I Dose Escalation; Phase II Cohort Expansion

mFOLFOX6 Regimen (Oxaliplatin/Leucovorin/5-FU) DRUG

Oxaliplatin 85 mg/m2 IV over 2 hours (Day 1), Leucovorin 400 mg/m2 IV over 2 hours (Day 1), 5-FU 400 mg/m2 IV bolus (Day 1) followed by 1200 mg/m2/day continuous IV infusion over 46-48 hours (total 2400 mg/m2), repeated every 2 weeks.

Phase II Cohort Expansion

FOLFIRI Regimen (Irinotecan/Leucovorin/5-FU) DRUG

Irinotecan 180 mg/m2 IV over 30-90 minutes (Day 1), Leucovorin 400 mg/m2 IV over 2 hours (Day 1), 5-FU 400 mg/m2 IV bolus (Day 1) followed by 1200 mg/m2/day continuous IV infusion over 46-48 hours (total 2400 mg/m2), repeated every 2 weeks.

Phase II Cohort Expansion

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years; voluntarily participate in this clinical trial, understand the study procedures, and have signed the informed consent form;
• ECOG performance status 0-1;
• Estimated survival time \>3 months;
• Histologically or cytologically confirmed metastatic and unresectable colorectal adenocarcinoma. For Phase I, Phase II Cohort 1, and the safety lead-in period of Cohorts 2/3: previously received one or more systemic treatments for metastatic colorectal cancer, and failed standard treatment, or have no standard treatment option, or standard treatment is not applicable at this stage; for the subsequent expansion phase of Phase II Cohorts 2/3: no prior systemic treatment for metastatic colorectal cancer;
• Genetic testing documentation (limited to PCR or NGS-based assays) must be provided prior to enrollment to demonstrate BRAF V600 mutation positivity;
• Agree to provide tumor tissue and/or blood samples;
• At least one measurable lesion according to RECIST 1.1 criteria;
• Laboratory values meeting the following standards:
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelets (PLT) ≥100×10⁹/L; hemoglobin (HB) ≥90 g/L (no transfusion or growth factor support within 7 days prior to testing); Total serum bilirubin ≤1.5×ULN; AST and/or ALT ≤2.0×ULN; if liver metastases are present, or if Gilbert syndrome (unconjugated hyperbilirubinemia) is clearly documented, AST and/or ALT ≤3.0×ULN, total bilirubin ≤1.5×ULN; Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (measured or calculated using the Cockcroft-Gault equation); Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN;
• Men and women of childbearing potential must agree to use appropriate contraceptive methods (hormonal, barrier method, or abstinence) during the study and for 3 months after the last dose; women of childbearing potential must have a negative pregnancy test within 7 days prior to dosing; male participants must not donate sperm from the start of treatment until 90 days after stopping treatment;
• Fully understand this clinical trial and voluntarily sign the written informed consent form.

You may not qualify if:

• History of other malignancies within the past 2 years (excluding skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, and other low-grade malignancies that have undergone radical treatment);
• Known RAS mutation;
• Known MSI-H/dMMR or unknown MSI/MMR status; if the participant has dMMR/MSI-H mCRC and is unable to receive immune checkpoint inhibitors due to existing medical conditions, enrollment is permitted (only for the subsequent expansion phase of Cohorts 2 and 3);
• Prior treatment with any BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib, etc.) or any EGFR inhibitor (e.g., cetuximab, etc.) prior to screening;
• History of acute or chronic pancreatitis within 6 months prior to the start of study treatment, or history of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to the start of study treatment;
• Impaired liver function, Child-Pugh Class B or C;
• Uncontrolled (including but not limited to requiring repeated drainage, symptomatic) moderate or larger pleural effusion, pericardial effusion, or ascites, as determined by the investigator;
• Known symptomatic central nervous system metastasis or leptomeningeal metastasis, or other evidence indicating that the individual's CNS metastasis or leptomeningeal metastasis is not controlled, and the investigator judges that the patient is unsuitable for enrollment;
• Individuals receiving long-term immunosuppressive therapy (e.g., cyclosporine) or requiring daily systemic corticosteroid therapy (e.g., \>20 mg prednisone or equivalent), excluding those using topical corticosteroids via nasal spray, inhalation, or other local routes;
• Systemic chemotherapy within 28 days prior to first dose, or immunotherapy (e.g., interleukin, interferon, thymosin, etc.), hormonal therapy, targeted therapy, or any investigational intervention within 14 days or 5 half-lives prior to first dose, whichever is shorter;
• Toxicity from prior antineoplastic therapy that has not resolved to CTCAE Grade ≤1 (excluding alopecia, skin toxicity, or other toxicities that the investigator considers to have no safety risk);
• Any condition affecting drug swallowing and severely affecting absorption of the study drug or pharmacokinetic parameters, including but not limited to active peptic ulcer disease, chronic gastroesophageal reflux disease (GERD), etc.;
• Severe or uncontrolled cardiac disease requiring treatment, including any of the following (but not limited to): QT interval prolongation on ECG corrected using Fridericia's formula, QTcF \>450 msec for males or \>470 msec for females; various clinically significant arrhythmias, including but not limited to ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, etc.; echocardiogram indicating left ventricular ejection fraction (LVEF) \<50%; myocardial infarction, unstable angina, NYHA Class III or IV heart failure within 6 months prior to first dose;
• Arterial/venous thromboembolic events within 6 months prior to first dose, with uncontrolled risk as judged, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, etc.; or known familial and/or acquired thrombophilia, such as inherited or acquired deficiencies of anticoagulant proteins, coagulation factors, fibrinolytic proteins, etc.;
• Severe or uncontrolled diabetes, hypertension (poorly controlled despite standard antihypertensive regimen, with systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg at screening), active bleeding, epilepsy (except when caused by intracranial tumor), chronic obstructive pulmonary disease, interstitial pneumonia, pulmonary interstitial fibrosis, Parkinson's disease, etc.;

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Oxaliplatin; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

lin shen

CONTACT

0086-10-88196561; doctorshenlin@sina.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 27, 2026
• Study Start: August 12, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: August 27, 2026

Record last verified: 2026-08

Locations

CN (1)