ctDNA-guided Treatment of TKI Plus PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer

NCT06543836 | Recruiting Phase 2

• 1 other identifier: NCC4663
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The efficacy of combining TKI with PD-1 inhibitor in the treatment of advanced MSS/pMMR colorectal cancer with low levels of maxVAF in peripheral blood ctDNA failed with standard treatment was assessed, compared to standard treatment as chosen by researchers.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival

  Up to 2 years

Secondary Outcomes (3)

• OS

  Up to 2 years

• ORR

  Up to 2 years

• DCR

  Up to 2 years

Study Arms (2)

PD-1 inhibitor+Tyrosine kinase inhibitor(TKI)

EXPERIMENTAL

PD-1 inhibitor: Sintilimab 200mg, d1, TKI: Fruquintinib 5mg Qd, d1-14, Q3w. Efficacy assessment every 2 cycles.

Drug: Sintilimab; Drug: Fruquintinib

Tyrosine kinase inhibitor(TKI)

ACTIVE COMPARATOR

The treatment regimen consists of the following options: Option 1: Fruquintinib 5mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months. Option 2: Regorafenib 160mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months.

Drug: Fruquintinib or Regorafenib

Interventions

Sintilimab DRUG

Sintilimab 200mg, d1, with a treatment cycle of 21 days, and efficacy assessment every 2 cycles.

Also known as: PD-1 inhibitor

PD-1 inhibitor+Tyrosine kinase inhibitor(TKI)

Fruquintinib or Regorafenib DRUG

The treatment regimen consists of the following options: Option 1: Fruquintinib 5mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months. Option 2: Regorafenib 160mg Qd, d1-21, Q4w, and efficacy assessment every 1.5 months.

Also known as: TKI

Tyrosine kinase inhibitor(TKI)

Fruquintinib DRUG

Fruquintinib 5mg Qd, d1-14, with a treatment cycle of 21 days, and efficacy assessment every 2 cycles.

Also known as: TKI

PD-1 inhibitor+Tyrosine kinase inhibitor(TKI)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range between 18 and 80 years old.
• ECOG performance status of 0 or 1.
• Histologically confirmed advanced or recurrent colorectal adenocarcinoma.
• Confirmed normal expression of mismatch repair proteins (pMMR) by immunohistochemistry or microsatellite stable (MSS) by PCR/next-generation sequencing.
• Blood ctDNA maxVAF \<6.5% as detected by NGS. blood samples of 8-10ml are to be collected from a qualified testing company for analysis.
• Metastatic colorectal cancer that has failed with previous treatment with fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan plus bevacizumab/cetuximab (left-side RAS/BRAF wildtype).
• At least 28 days since the last systemic therapy (oral fluoropyrimidine ≥ 14 days), with the option of receiving palliative radiation therapy to limited areas if completed more than 3 weeks prior.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1).
• Expected survival of at least 3 months.
• Adequate organ and bone marrow function, with laboratory values within the following limits within 7 days before enrollment:
• Complete blood count: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, Platelet count (PLT) ≥100×10\^9/L, Hemoglobin (HGB) ≥9.0 g/dL.
• Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN, or ≤5× ULN in the presence of liver metastasis.
• Kidney function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50ml/min, Urinalysis showing urine protein \<2+, for patients with baseline urine protein ≥2+, 24-hour urine protein collection should show \<1g.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 times ULN.
• Normal electrocardiogram, left ventricular ejection fraction (LVEF) ≥50%.

You may not qualify if:

• Patients with a history of prior treatment with fruquintinib or similar small molecule oral targeted drugs primarily aimed at anti-angiogenesis (including marketed or investigational drugs).
• Patients with a history of prior treatment with other PD-1/PD-L1/CTLA-4 antibody therapies or other immunotherapies targeting PD-1/PD-L1/CTLA-4.
• Patients who experienced severe hypersensitivity reactions after monoclonal antibody administration in the past.
• Patients with any active autoimmune disease or a history of autoimmune diseases (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, and patients requiring bronchodilators for medical intervention for asthma cannot be included). however, the following patients are allowed to be included: patients with vitiligo, psoriasis, alopecia that do not require systemic treatment, well-controlled type I diabetes, and hypothyroidism with normal thyroid function under replacement therapy.
• Patients who require immunosuppressive agents, systemic corticosteroids, or absorbable local steroid therapy for achieving immunosuppression (dose \>10mg/day prednisone or equivalent) and are still on continued therapy within 2 weeks of initial dosing.
• Patients with various factors affecting oral drug intake (such as dysphagia, post-gastrointestinal surgery, chronic diarrhea, and intestinal obstruction).
• Patients with uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Patients with any signs or history of bleeding diathesis regardless of severity, patients who experienced any bleeding event ≥CTCAE Grade 3 within 4 weeks before initial dosing, or patients with unhealed wounds, fractures, active peptic ulcers, ulcerative colitis, or other gastrointestinal diseases with active bleeding or other conditions deemed by the investigator to potentially cause severe gastrointestinal bleeding or perforation.
• Patients with known brain metastases with a history of organ transplantation.
• Patients who received approved or investigational anti-tumor treatments within 4 weeks before the start of the study, including but not limited to chemotherapy, surgery, radiotherapy (within 3 weeks), biologically targeted therapy, interventional therapy, immunotherapy, and traditional Chinese medicine treatment for cancer (as per the indications in the traditional Chinese medicine instructions, participants can be included after a 2-week washout period) (Note: oral fluoropyrimidine drugs for less than 14 days, patients with adverse events from previous treatments, excluding alopecia, not recovered to ≤CTCAE Grade 1).
• Patients vaccinated with preventive or attenuated vaccines within 4 weeks before the first dose.
• Patients with any severe and/or uncontrolled diseases, including:
• patients with suboptimal blood pressure control (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥90 mmHg).
• patients who had thrombotic events, cerebrovascular accidents, myocardial infarctions, ≥Grade 2 congestive heart failure, or requiring treatment for arrhythmias (including QTc ≥480ms) within 6 months before the first dose.
• patients with active or uncontrolled severe infections (≥CTCAE Grade 2 infections), tuberculosis patients.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sintilimab; Immune Checkpoint Inhibitors; HMPL-013; regorafenib

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)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Aiping Zhou, M.D.

  Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aiping Zhou, M.D.

CONTACT

8610-13691161998; zhouap1825@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: August 9, 2024
• Study Start: December 1, 2023
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)