XS-03 in Combination With FOLFOX or FOLFIRI and Bevacizumab for Treatment of Metastatic Colorectal Cancer Patients With RAS Mutation

NCT06936527 | Enrolling By Invitation Phase 1

• 1 other identifier: XS-03-II201
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

XS-03 in combination with FOLFOX or FOLFIRI and Bevacizumab for treatment of metastatic colorectal cancer patients with RAS mutation

Conditions

Colorectal Cancer; Metastatic Colorectal Cancer With RAS Mutation

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Number of participants with Dose-limiting Toxicities (DLTs) in experimental arm of XS-03 in combination with FOLFOX or FOLFIRI and Bevacizumab

  Dose-limiting toxicities were defined as events related to XS-03 that were considered an adverse reaction or suspected adverse reaction during the first cycle of treatment

  up to day 28

• Phase 1b: Determine the Maximum Tolerated Dose (MTD) in experimental arm of XS-03 in combination with FOLFOX or FOLFIRI and Bevacizumab

  MTD is defined as at most 1 patient out of 6 experiencing DLT

  up to day 28

• Phase 2: Objective Response Rate (ORR) of two experimental arms and comparator arm

  Defined as the percentage of participants that achieve a best overall response of complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria)

  up to 18 months after first dose of last patient

Secondary Outcomes (15)

• Phase 1b: Objective Response Rate (ORR) of all treated participants

  up to 18 months after first dose of last patient

• Duration of response (DOR) of all treated participants

  up to 18 months after first dose of last patient

• Progression-free survival (PFS) of treated participants

  up to 18 months after first dose of last patient

• Overall survival (OS) of treated participants

  up to 18 months after first dose of last patient

• Number of Participants With Adverse Events (AEs) of treated participants

  up to 28 days after last dose of study drug

Study Arms (3)

Experimental arm 1: XS-03 + FOLFOX/FOLFIRI + Bevacizumab

EXPERIMENTAL

Phase 1b: XS-03 escalating orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combination with FOLFOX or FOLFIRI and bevacizumab. FOLFOX (85 mg/m\^2 oxaliplatin, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU) , 5 mg/kg bevacizumab FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU), 5 mg/kg bevacizumab

Biological: Drug: XS-03, Biological: Bevacizumab, Drug: FOLFOX, Drug: FOLFIRI

Experimental arm 2: XS-03 + FOLFOX/FOLFIRI + Bevacizumab

EXPERIMENTAL

Phase 2: XS-03 Recommended Phase 2 Dose (RP2D) and selected one more dosage orally Day 1 through Day 5 and Day 15 through Day 19 of each 28-day cycle in combinationwith FOLFOX or FOLFIRI and bevacizumab. FOLFOX (85 mg/m\^2 oxaliplatin, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU) , 5 mg/kg bevacizumab FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU), 5 mg/kg bevacizumab

Biological: Drug: XS-03

Comparator: FOLFOX/FOLFIRI + Bevacizumab

ACTIVE COMPARATOR

Phase 2: Comparator arm treat with FOLFOX or FOLFIRI + bevacizumab intravenously. FOLFOX (85 mg/m\^2 oxaliplatin, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU) , 5 mg/kg bevacizumab FOLFIRI (180 mg/m\^2 irinotecan, 400 mg/m\^2 leucovorin, 400 mg/m\^2 bolus 5-fluorouracil (5-FU), and 2400 mg/m\^2 continuous intravenous infusion 5-FU), 5 mg/kg bevacizumab

Biological: Biological: Bevacizumab, Drug: FOLFOX, Drug: FOLFIRI

Interventions

Drug: XS-03, Biological: Bevacizumab, Drug: FOLFOX, Drug: FOLFIRI BIOLOGICAL

XS-03 orally Bevacizumab intravenously FOLFOX intravenously FOLFIRI intravenously

Experimental arm 1: XS-03 + FOLFOX/FOLFIRI + Bevacizumab

Drug: XS-03 BIOLOGICAL

XS-03 orally

Experimental arm 2: XS-03 + FOLFOX/FOLFIRI + Bevacizumab

Biological: Bevacizumab, Drug: FOLFOX, Drug: FOLFIRI BIOLOGICAL

Bevacizumab intravenously FOLFOX intravenously FOLFIRI intravenously

Comparator: FOLFOX/FOLFIRI + Bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in the clinical trial and sign the informed consent form.
• Age ≥18 and ≤ 70 years. No gender restrictions.
• Patients with histologically and/or cytologically confirmed metastatic colorectal cancer who are not suitable for surgical treatment.
• Documentation of RAS mutation. The previously gene test report issued by qualified testing institution is acceptable. BRAF status is not restricted.
• Consent to provide tumor tissue samples and peripheral blood for biomarker analysis.
• Has measurable extracranial lesion according to RECIST v1.1 criteria, defined as at least one lesion that has not received radiotherapy. For previously radiotherapy lesion, there must be imaging evidence of progression after radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
• Expected life expectancy ≥ 6 months.
• The patient has adequate hepatic, renal and bone marrow function.
• For a woman of child-bearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. Woman of child-bearing potential and fertile men must agree to use adequate contraception for the duration of study participation and for 6 months after the last dose.

You may not qualify if:

• Patients with known high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) primary or metastatic colorectal cancer and suitable for immune checkpoint inhibitor treatment assessed by investigators.
• Previously received bevacizumab and its biosimilar therapy. (Only for phase II)
• Central nervous system metastases which are symptomatic or require therapy.
• Imaging shows major blood vessel invasion (such as the aorta, pulmonary artery, pulmonary vein, vena cava, etc.).
• Adverse events and/or complications that caused by previous antitumor therapy have not recovered to baseline level or ≤ CTCAE grade 1.
• With a history of other malignancies within 5 years or with other malignancies currently prior to screening, except colorectal cancer. Exception: curatively treated early-stage malignancies (in situ carcinoma or stage I tumors), such as adequately treated basal cell or squamous cell skin cancer or in situ cancer of the cervix.
• Patients have a significant risk of bleeding.
• Patients have a significant risk of thrombus.
• Patients have severe cardiovascular disease, including but not limited to: Ischemic heart disease within the past 6 months prior to screening; coronary artery disease post-surgery or stent implantation within 6 months; New York Heart Association (NYHA) functional classification ≥ Class II within 6 months prior to screening; or known left ventricular insufficiency (LVEF \<50%)；severe arrhythmia requiring clinical intervention; any other cardiovascular disease that researchers regard the patient unsuitable for participation in the study.
• Patients with a significantly increased risk of QTc prolongation.
• Patients unable to swallow drugs or have severe diseases that significantly affect drug absorption.
• Patients have one of the following viral active infections: active hepatitis B or C; human immunodeficiency virus (HIV) infection; active syphilis
• During screening, the presence of interstitial lung disease, interstitial pneumonia, pulmonary interstitial fibrosis requiring therapy, or a history of pneumonia caused by tyrosine kinase inhibitors.
• Patients received radiotherapy within the past 4 weeks prior to the first first dose of study drug.
• Patients received therapeutic surgeries (excluding diagnosis, biopsy, or drainage procedures) within the past 4 weeks prior to the first dose of study drug, including local treatments such as radiofrequency ablation for liver metastases, or are expected to have major surgeries during the study period.

Sponsors & Collaborators

• NovaOnco Therapeutics Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folfox protocol

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

Study Design

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

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 20, 2025
• Study Start: May 23, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)