Phase II Study of Anti-PD-1/VEGF Bispecific Antibody Ivonescimab in Patients With Previously Treated Metastatic Colorectal Cancer

NCT06959550 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0278NCI-2025-03211
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if ivonescimab can help to control previously treated, metastatic colorectal cancer.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 1. Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Treatment with Ivonescimab

EXPERIMENTAL

Participants will be assigned to the study using a Bayesian Optimal Phase 2 (BOP2) design

Drug: Ivonescimab

Interventions

Ivonescimab DRUG

Given by IV

Treatment with Ivonescimab

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent
• Male and female adult participants 18 years of age or older on day of signing informed consent.
• Histological or cytological confirmed advanced, metastatic adenocarcinoma of colon or rectum.
• Known MMR or MSI status performed by local standard of practice. (e.g., IHC and/or PCR, next-generation sequencing)
• Cohort-specific criteria
• Cohort 1: MSI-H/dMMR: ICI-refractory
• dMMR or MSI-H per local testing
• Demonstrated radiographic or clinical disease progression following treatment with immune checkpoint inhibitors including anti-PD-1 +/- anti-CTLA-4 therapy. If progression occurred after first imaging assessment, then pseudo-progression should be excluded by concurrent carcinoembryonic antigen (CEA) or other tumor marker or ctDNA elevation, or clinical symptom progression, or short-interval repeat imaging confirming progression.
• Must have received at least 2 doses of a PD1/PD-L1 inhibitor.
• Progressive disease either during therapy or within 3 months of last dose of therapy.
• No serious adverse immune-related adverse events (grade 3 or higher) with previous immune checkpoint therapy, that were symptomatic and required prolonged immunosuppression (\>6 weeks).
• Cohort 2: pMMR with liver metastases
• pMMR or non-MSI-H per local testing
• Presence of active liver metastases per radiographic imaging
• Patients with any bulky liver metastases measuring \>5.0 cm are not eligible

You may not qualify if:

• Any single liver metastasis \>5.0 cm (Cohort 2 only)
• Except for MSI-H/dMMR tumors, prior therapy with PD-1, PD-L1, or CTLA-4 inhibitors (Cohorts 2 and 3 only).
• Patient who discontinued prior therapy with immune checkpoint inhibitors due to Grade 2 neurologic, cardiac, or ophthalmologic events or recurrent Grade 2 pneumonitis are not eligible for the trial (Cohort 1 only).
• Systemic anti-cancer treatment within 14 days or less than 5 half-lives (whichever is shorter) of the first dose of study treatment.
• History of arterial thromboembolic event, venous thromboembolic event of grade 3 and above as specified in NCI CTCAE v5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment
• Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification . grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
• Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment
• Poorly controlled hypertension with repeated systolic blood pressure . 150 mmHg or diastolic blood pressure . 100 mmHg after oral antihypertensive therapy
• Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to randomization, however the following will be allowed: a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. b. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted
• Know history of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominopelvic fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to enrollment
• History of perforation of the gastrointestinal tract and/or fistula, gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), or extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to:
• Hemoptysis (defined as coughing up . 0.5 teaspoon of fresh blood or small blood clots. Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed
• Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
• Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not permitted. The use of full-dose anticoagulants is permitted if the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Akesobio Australia Pty Ltd: collaborator
• Summit Therapeutics: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

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

Study Officials

• Saurav Haldar, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saurav Haldar, MD

CONTACT

713-792-5111; GIClinicalTrials@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: May 6, 2025
• Study Start: July 28, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2025-11

Locations

US (1)