Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

Phase 1

Not yet recruiting

• Conditions: To Evaluate the Efficacy of Fruquintinib and Pirfenidone in Combination With Anti-PD-1 Antibody in Colorectal Carcinoma; To Evaluate Whether Pirfenidone Can Reshape the Tumor Microenvironment in Colorectal Cancer; Combination of Fruquintinib and Anti-PD-1 Antibody Was Reported to Improve Patient Prognosis in Colorectal Cancer
• Interventions: Drug: Pirfenidone; Drug: Fruquintinib; Drug: Pembrolizumab

• Registration Number: NCT06484153
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of fruquintinib and pirfenidone in combination with anti-PD-1 antibody in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.

Detailed Description

In this study, we explored the potential effectiveness of fruquintinib and pirfenidone in combination with anti-PD-1 antibody, in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. 25 patients were included.

Study Timeline

• Study First Submitted: 2024-05-24
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-01
• Last Update Submitted: 2024-07-01
• Study First Posted: 2024-07-03
• Last Update Posted: 2024-07-03
• Study Start: 2024-07-22
• Primary Completion: 2026-07-22
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.

2. Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).

3. Subjects must have failed at least two lines of prior treatment.

4. Subjects must have one measurable lesion according to RECIST v1.1 at least.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. 18-75 years old.

6. Life expectancy of at least 12 weeks. 8. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

Exclusion Criteria

1. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or Pirfenidone.
2. Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.
3. Received radiotherapy with 4 weeks of the first dose of study medication.
4. Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
5. Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.
6. Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
7. Interstitial lung disease requiring corticosteroids.
8. Active or poorly controlled serious infections.
9. Significant malnutrition.
10. Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
11. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
12. Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.
13. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
14. Any life-threatening bleeding within 3 months prior to the enrollment.
15. High risk of bleeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Pembrolizumab	Pembrolizumab intravenous (IV) 200mg flat dose day 1 then every 3 weeks. Fruquintinib orally (PO) 3mg po qd. Pirfenidone (Esbriet) orally (PO) with food according to this schedule: two dose groups: 200mg, TID, po;500mg, TID ,po. Using "3-3" design, the observation period of DLT was 28 days.
Treatment	Pirfenidone	Pembrolizumab intravenous (IV) 200mg flat dose day 1 then every 3 weeks. Fruquintinib orally (PO) 3mg po qd. Pirfenidone (Esbriet) orally (PO) with food according to this schedule: two dose groups: 200mg, TID, po;500mg, TID ,po. Using "3-3" design, the observation period of DLT was 28 days.
Treatment	Fruquintinib	Pembrolizumab intravenous (IV) 200mg flat dose day 1 then every 3 weeks. Fruquintinib orally (PO) 3mg po qd. Pirfenidone (Esbriet) orally (PO) with food according to this schedule: two dose groups: 200mg, TID, po;500mg, TID ,po. Using "3-3" design, the observation period of DLT was 28 days.

Primary Outcome Measures

Name	Time	Method
Occurrence of Grade 4 toxicity	Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days)	CTCAE v5.0
Progression Free Survival (PFS)	2 year	The time from enrollment until tumor progression or death from any cause, whichever occurred first
Occurrence of Grade 3 toxicity	Cycle 1 day 1 to Cycle 3 day 1 (Each cycle is 21 days	CTCAE v5.0

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	2 year	The proportion of patients with a PR or CR
Overall Survival (OS)	2 year	The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date
Disease control rate (DCR)	2 year	The proportion of patients with a PR, CR, or SD
Duration of response (DoR)	2 year	For patients who achieved a complete response (CR) or partial response (PR), the time from the first tumor assessment demonstrating response until disease progression or death, whichever occurred first