Combination of LTC004 and Regorafenib to Treat Patients With Advanced/Metastatic CRC

NCT06322563 | Not Yet Recruiting Phase 2

• 1 other identifier: LTC004-202
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II clinical study to evaluate the safety, tolerability and preliminary antitumor activity of LTC004 in combination with regorafenib in patients with mCRC. A safety introductory trial was conducted to receive LTC004 in combination with regorafenib before starting the formal trial. After completing a 28-day safety assessment, safety will be confirmed before entering the formal trial phase. Further evaluation of the safety and efficacy of LTC004 in combination with regorafenib in the treatment of mCRC

Conditions

Advanced/Metastatic Colorectal Cancer

Keywords

mCRC

Outcome Measures

Primary Outcomes (2)

• Treatment-Emergent Adverse Events-Safety and Tolerability

  TEAE and changes in safety indicators (12-ECG,Laboratory inspection items,Cardiopulmonary function and so on)before and after administration

  up to 12 months

• SAE-Safety and Tolerability

  SAE and changes in safety indicators (12-ECG,Laboratory inspection items,Cardiopulmonary function and so on)before and after administration

  up to 12 months

Secondary Outcomes (4)

• ORR

  up to 12 months

• DCR

  up to 12 months

• PFS

  up to 12 months

• OS

  up to 12 months

Study Arms (2)

Safety introduction trial：LTC004+regorafenib

EXPERIMENTAL

LTC004 in combination with regorafenib safety introduction trial and completing a 28-day safety assessment

Drug: LTC004+regorafenib

Formal trial phase：LTC004+regorafenib

EXPERIMENTAL

After Safety introduction trial, safety will be confirmed before entering the formal trial phase.Further evaluation of the safety and efficacy of LTC004 in combination with regorafenib in the treatment of mCRC

Drug: LTC004+regorafenib

Interventions

LTC004+regorafenib DRUG

LTC004,90μg/kg,IV,Day 1,Q3W; Regorafenib:Orally once daily for the first 21 days of each cycle, with 28 days as 1 cycle. Cycle 1 was dose-escalation with a starting dose of 80 mg/d, increasing by 40 mg per week until 160 mg/d, i.e., 80 mg/d in week 1 (D1\~D7), 120 mg/d in week 2 (D8\~D14), and 160 mg/d in week 3 (D15\~D21);

Formal trial phase：LTC004+regorafenib; Safety introduction trial：LTC004+regorafenib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years.
• Non-radical resectable metastatic colorectal cancer confirmed by histology or cytology.
• Those who have progressed on, or are intolerant to, at least one prior first- and second-line systemic antitumor therapy for metastatic colorectal cancer. Patients must have received fluorouracil, oxaliplatin, and irinotecan-based chemotherapy, and patients with mCRC who have previously received or are not candidates for anti-VEGF therapy, anti-epidermal growth factor receptor therapy (RAS wild-type).
• Pre-existing MMR, MSS, HER2, PD-L1, RAS, and BRAF status with corresponding supporting documentation.
• At least one measurable tumor lesion based on RECIST V1.1 criteria.
• ECOG PS ≤1.
• Expected survival ≥12 weeks.
• able to Swallow whole pills.
• Adequate organ function.
• Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for 6 months after the last infusion of LTC004.
• Understands and provides written informed consent and willing to follow the requirements specified in protocol.

You may not qualify if:

• History of severe hypersensitivity reactions to other mAbs.
• Untreated, unstable or uncontrolled central nervous system (CNS) metastases.
• Tumor invasion of vital arteries resulting in high risk of bleeding, significant risk of perforation or already formed fistulae.
• Patients with uncontrolled pleural effusion, pericardial effusion or abdominal effusion as judged by the investigator at screening.
• Patients with untreated or clinically symptomatic spinal cord compression that has not been controlled.
• Previous antitumor regimens include immunotherapies such as PD-1/L1 inhibitors, LAG3, TIGIT, IL-2, IL-15, CD3-like immunoagonists, and other cellular therapies, as well as other TKI agents (e.g., furaquintinib, regorafenib, etc.).
• ≥2 malignant tumors within 5 years prior to first dose of drug.
• Patients who have received any chemotherapy or anti-tumor monoclonal antibody drugs within 4 weeks prior to the first dose of study drug (excluding mitomycin and nitrosoureas within 6 weeks prior to the first dose of study drug; small molecule targeted drugs within 2 weeks prior to the first dose of study drug; Chinese medicine therapy (Chinese medicine therapy with clear anti-tumor indications in the package insert within 4 weeks prior to the first dose of study drug.
• Moderate to severe dyspnea at rest due to advanced cancer or its complications, severe primary lung disease, current need for continuous oxygen therapy, or clinically active interstitial lung disease (ILD) or pneumonia; Grade ≥3 interstitial pneumonia during prior antineoplastic therapy.
• Presence of severe infections including, but not limited to, bacteremia and severe pneumonia requiring hospitalization within 4 weeks prior to the first dose; active infections with CTCAE ≥ grade 2 requiring treatment with systemic antibiotics within 2 weeks prior to the first dose.
• History of serious cardiovascular disease.
• Previous total gastrectomy, chronic diarrhea, active inflammatory gastrointestinal disease, or any other condition causing malabsorption syndrome.
• Active bleeding disorder, including gastrointestinal bleeding, as evidenced by vomiting of blood, profuse hemoptysis, or black stools, in the 6 months prior to enrollment.
• Active hepatitis B (hepatitis B virus DNA measurement ≥1000 copies/mL or 200 IU/mL); hepatitis C infection (hepatitis C antibody positive and HCVRNA above the lower limit of detection in research centers); syphilis infection, active tuberculosis.
• Active, or previous autoimmune disease with potential for recurrence at the time of screening.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

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

Central Study Contacts

Ting Deng

CONTACT

15802243063; 18526812877@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 21, 2024
• Study Start: April 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: March 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)