Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer

A Phase 2 Clinical Trial of Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer

This is an open-label Phase 2 study to evaluate the safety and efficacy of Tovecimig combined with FOLFIRI in patients who have received one prior line of therapy for advanced or metastatic colorectal cancer (CRC).

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Colorectal Cancer; Colorectal Cancer
• Intervention / Treatment: Biological: Tovecimig; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-Fluorouracil (5-FU)

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Olivia Aranha, MD, PhD; Phone Number: 557-747-2105; Email: oaranha@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Sub-Investigator: Esther Lu, PhD
      • Contact: Olivia Aranha, MD, PhD; Phone Number: 557-747-2105; Email: oaranha@wustl.edu
      • Principal Investigator: Olivia Aranha, MD, PhD
      • Sub-Investigator: Erika Belmont, MD
      • Sub-Investigator: Roheena Z Panni, MD, MPHS
      • Sub-Investigator: Valerie Prashad, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed CRC.
• Patient must have undergone resection of his/her primary tumor either as part of treatment for early stage disease with subsequent metastatic progression or due to a tumor related complication in the metastatic setting (e.g. bowel obstruction).
• Measurable disease per RECIST 1.1.
• Patient must have advanced or metastatic disease, and have progressed on one line of standard of care therapy in the advanced/metastatic setting
• At least 18 years of age.
• ECOG performance status ≤ 2

• Adequate bone marrow and organ function as defined below:

  • Absolute neutrophil count ≥ 1.5 K/cumm
  • Platelets ≥ 100 K/cumm
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 x IULN or ≤ 2.0 mg/dL in presence of liver metastases
  • AST(SGOT)/ALT(SGPT) ≤ 3x IULN or ≤ 5x IULN in presence of liver metastases
  • Creatinine clearance > 50 mL/min by Cockcroft-Gault
• The effects of Tovecimig and FOLFIRI on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after the last dose of Tovecimig or any component of FOLFIRI. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Patients with MSI-H status.
• Intact primary tumor that has not been resected.

• More than one line of prior therapy for advanced or metastatic CRC.

  *If FOLFIRI/FOLFOXIRI was given in the first line, it must have been completed ≥ 6 months before study start date.

• Surgery or major procedure, or systemic anticancer therapy within 4 weeks prior to C1D1.
• Radiation therapy within 2 weeks prior to C1D1.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Receipt of any other investigational agents within 4 weeks prior to C1D1, with exception of investigational imaging agents.
• Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression.
• Prior history of diseases/conditions that elevates the patient's risk of hemorrhage, such as a bleeding diatheses, history of prior bowel perforation, or clinically significant active bleeding (i.e. hemoptysis larger than a tablespoon within 3 weeks prior to C1D1).
• Recent history of paracentesis (within 3 weeks prior to C1D1) or current indwelling catheter.
• A history of hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to Tovecimig (i.e. humanized/human monoclonal antibody drugs), FOFLIRI, or other agents used in the study.
• Use of anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylaxis) purpose within 10 days of C1D1.
• Use of aspirin, other NSAIDs (i.e. naproxen, ibuprofen), or other antiplatelet drugs within 10 days of C1D1.
• Uncontrolled intercurrent illness/infection requiring ongoing systemic antibiotics, antivirus drugs, or other uncontrolled active acute infectious diseases.
• A history of CHF (NYHA class II or higher) with 5 years prior to C1D1, LVEF < 50% on screening TTE/MUGA, uncontrolled hypertension (defined as SBP/DBP greater than 140/90 despite best supportive care at any time during screening), pulmonary hypertension, myocardial infarction, uncontrolled arrhythmia, unstable angina, or any significant valvular disease.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of C1D1.
• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tovecimig and Irinotecan + Leucovorin + 5-Fluorouracil (FOLFIRI regimen); Treatment will be administered in 28-day cycles. On Day 1 and 15 of each cycle, patients will receive Tovecimig followed by the FOLFIRI regimen.

Biological: Tovecimig; Tovecimig is provided in 10 mg/kg dose intravenously over the course of 60 minutes on Day 1 and Day 15 of a 28-day cycle.; Other Names: CTX-009; Drug: Irinotecan; Standard of care irinotecan will be given at a dose of 180 mg/m^2 intravenously on Day 1 and Day 15 of each 28-day cycle as part of the FOLFIRI treatment regimen.; Other Names: Camptosar; Drug: Leucovorin; Standard of care leucovorin will be given at a dose of 400 mg/m^2 intravenously on Day 1 and Day 15 of each 28-day cycle as part of the FOLFIRI treatment regimen.; Other Names: Vykoura; Drug: 5-Fluorouracil (5-FU); Standard of care 5-FU will be given at a dose of 2400 mg/m^2 in continuous infusion over 46 hours on Days 1-2 and Days 15-16 of each 28-day cycle as part of the FOLFIRI treatment regimen.; Other Names: 5-FU; Adrucil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Defined as the proportion of patients who have a partial response (PR) or complete response (CR) per RECIST 1.1. CR is defined as disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Start of treatment to completion of treatment (estimated time up to 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from date of start of treatment to the date of disease progression or death, whichever occurs first. Alive patients without disease progression are censored at the last follow-up otherwise. PFS will be assessed using the Kaplan-Meier method. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).	Start of treatment to date of progression or death whichever is earlier (estimated time to be up to 36 months)
Overall Survival (OS)	OS is defined as the time from date of treatment start to the date of death. Alive patients are censored at the last follow-up otherwise. OS will be assessed using the Kaplan-Meier method.	Start of treatment to date of death (estimated time to be up to 36 months)
Number and types of adverse events (AEs)	As assessed by CTCAE v6.0.	Start of treatment to 30 days after completion of treatment (estimated total time to be 13 months)
Disease Control Rate (DCR)	DCR is defined as complete response (CR) plus partial response (PR) plus stable disease (SD) as assessed per RECIST v1.1 as best overall response. CR is defined as disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Time of best response through completion of follow-up (estimated total time to be up to 36 months)
Change in quality of life as measured by Eastern Cooperative Oncology Group (ECOG) performance status	ECOG performance scale is graded as follows: Grade 0: Normal activity. Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work). Grade 2: In bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours. Grade 3: In bed >50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. Grade 4:100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. Grade 5: Death A lower ECOG performance score indicates a better quality of life.	Baseline to end of treatment (total estimated time 12 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Compass Therapeutics
• Investigators: Principal Investigator: Olivia Aranha, MD, PhD, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2032

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Microsatellite stable; Tovecimig
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Irinotecan; Fluorouracil; Leucovorin
• Other Study ID Numbers: 26-x148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes