Trial: Phase III Study of Ivonescimab or Bevac…

Trial Details

Sponsor: Summit Therapeutics (industry)

Phase: 3

Start date: Nov. 14, 2025

Planned enrollment: 600

Trial ID: NCT07228832

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Ivonescimab (AK112/SMT112)

Overview

Ivonescimab (AK112/SMT112) is a bispecific antibody studied primarily in advanced non-small-cell lung cancer (NSCLC). It has human phase 3 results, including trials comparing it with established immunotherapy or adding it to chemotherapy. The results apply to different patient groups and should not be treated as interchangeable. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Ivonescimab targets both PD-1, an immune checkpoint, and VEGF-A, a protein involved in blood-vessel formation. It is designed to counter immune suppression and tumor angiogenesis simultaneously; whether this design provides a benefit depends on the clinical setting. (pmc.ncbi.nlm.nih.gov)

Efficacy

Previously untreated, PD-L1-positive advanced NSCLC: In the China-based HARMONi-2 trial (398 patients), median progression-free survival was 11.1 months with ivonescimab versus 5.8 months with pembrolizumab. A prespecified interim overall-survival analysis presented in September 2026 reported 30.8 versus 22.6 months, respectively; those survival findings were conference results rather than the published trial’s final analysis. (pubmed.ncbi.nlm.nih.gov)
Previously untreated advanced squamous NSCLC: In HARMONi-6, ivonescimab plus chemotherapy yielded median progression-free survival of 11.1 versus 6.9 months with tislelizumab plus chemotherapy. A subsequently published interim analysis found median overall survival of 27.9 versus 23.7 months. (pubmed.ncbi.nlm.nih.gov)
EGFR-mutated NSCLC after EGFR-targeted therapy: In the global HARMONi trial, adding ivonescimab to chemotherapy improved median progression-free survival (6.8 versus 4.4 months). Median overall survival was 16.8 versus 14.0 months, but the prespecified primary overall-survival analysis did not establish a statistically significant benefit. In the separate China-based HARMONi-A trial, the objective response rate was 50.6% versus 35.4% with chemotherapy alone, and a later analysis reported an overall-survival benefit. (pubmed.ncbi.nlm.nih.gov)

Safety

Grade 3 or higher treatment-related adverse events were more frequent with ivonescimab in some comparisons: 29% versus 16% with pembrolizumab in HARMONi-2, and 64% versus 54% with tislelizumab plus chemotherapy in HARMONi-6. In the global HARMONi trial, prominent grade 3–4 events included reduced blood-cell counts; treatment-related deaths occurred in both study groups. These rates come from different regimens and populations and cannot be directly compared across trials. (pubmed.ncbi.nlm.nih.gov)

TrialFetch AI Analysis

Goal: Determine whether ivonescimab plus mFOLFOX6 improves outcomes compared with bevacizumab plus mFOLFOX6 as first-line treatment for metastatic colorectal cancer.

Patients: Patients with confirmed, unresectable metastatic colorectal cancer, ECOG performance status 0–1, at least one measurable noncerebral lesion, and no prior systemic therapy for metastatic disease. Patients with MSI-H/dMMR disease, known BRAF V600E mutation, prior colorectal cancer immunotherapy or antiangiogenic therapy, or significant gastrointestinal obstruction are excluded.

Design: Multicenter, multiregional, randomized, double-blind, active-controlled study with 1:1 assignment.

Treatments: Both groups receive intravenous mFOLFOX6 every 2 weeks for up to eight cycles, followed by fluorouracil and leucovorin maintenance every 2 weeks for up to 2 years. The experimental group also receives ivonescimab throughout treatment; the comparator group receives bevacizumab. Ivonescimab is a bispecific antibody targeting PD-1 and VEGF-A, intended to address immune suppression and angiogenesis simultaneously. Phase 3 studies in non-small-cell lung cancer have reported improved progression-free survival with ivonescimab-containing regimens in several settings, but those results do not establish benefit in colorectal cancer. Bevacizumab is an anti-VEGF therapy used with chemotherapy for metastatic colorectal cancer.

Outcomes: The primary endpoint is progression-free survival by independent radiologic review under RECIST v1.1. Secondary endpoints include overall survival, objective response rate, duration of response, adverse events, and clinically significant laboratory abnormalities.

Burden on patient: Moderate. Intravenous treatment every 2 weeks, potentially continuing as maintenance for up to 2 years, requires repeated clinic visits. Imaging and laboratory monitoring add to the burden, although these are broadly consistent with care for patients receiving metastatic colorectal cancer therapy. No extra research biopsies or intensive pharmacokinetic sampling are specified.

Last updated: Sep 2026

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Montreal, Quebec, H4A 3J1, Canada

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Hokkaido, 060-8648, Japan

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Fukuoka, 812-8582, Japan

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Chiba, 260-8717, Japan

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Aichi, 464-8681, Japan

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Tokyo, 104-0045, Japan

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Osaka, 541-8567, Japan

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Gifu, 501-1194, Japan

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Rio Piedras, 00935, Puerto Rico

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London, England, EC1M 6BQ, United Kingdom

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Goodyear, Arizona, 85338, United States

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Orange, California, 92868, United States

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Torrance, California, 90503, United States

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Upland, California, 91786, United States

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West Hollywood, California, 90048, United States

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Pasadena, California, 91030, United States

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Beverly Hills, California, 90212, United States

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Cerritos, California, 90703, United States

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Corona, California, 92882, United States

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Duarte, California, 91010, United States

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Huntington Beach, California, 92648, United States

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Irvine, California, 92612, United States

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Irvine, California, 92618, United States

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Los Angeles, California, 90027, United States

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Los Angeles, California, 90067, United States

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Murrieta, California, 92562, United States

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New Haven, Connecticut, 06520-8028, United States

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Norwich, Connecticut, 06360, United States

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Hialeah, Florida, 33013, United States

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Orlando, Florida, 32806, United States

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Port Saint Lucie, Florida, 34952, United States

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Newnan, Georgia, 30265, United States

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O'Fallon, Illinois, 62269, United States

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Chicago, Illinois, 60611, United States

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Elmhurst, Illinois, 60540, United States

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Fort Wayne, Indiana, 46804, United States

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Edgewood, Kentucky, 41017, United States

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Saint Louis Park, Minnesota, 55426, United States

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Billings, Montana, 59102, United States

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Lincoln, Nebraska, 68506, United States

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New Brunswick, New Jersey, 08901, United States

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The Bronx, New York, 10461, United States

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Mineola, New York, 11501, United States

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New York, New York, 10016, United States

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Cincinnati, Ohio, 45220, United States

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Philadelphia, Pennsylvania, 19111, United States

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Philadelphia, Pennsylvania, 19140, United States

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Hermitage, Tennessee, 37129, United States

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Fort Worth, Texas, 76104, United States

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Salt Lake City, Utah, 84106, United States

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Charlottesville, Virginia, 22908, United States

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Spokane, Washington, 99208, United States

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Tacoma, Washington, 98405, United States

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Charleston, West Virginia, 25304, United States

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A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination With FOLFOX Versus Bevacizumab in Combination With FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: Ivonescimab (AK112/SMT112)

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (54)

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