Trial: Clinical Study of Ivonescimab for First…

Trial Details

Sponsor: Summit Therapeutics (industry)

Phase: 3

Start date: Oct. 26, 2023

Planned enrollment: 400

Last updated in HealthScout: Dec 2024

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Ivonescimab (AK112/SMT112)

Overview

Ivonescimab, also known as AK112 or SMT112, is a first-in-class, humanized tetravalent bispecific antibody designed to simultaneously target programmed death-1 (PD-1) and vascular endothelial growth factor A (VEGF-A). This dual-targeting approach aims to enhance antitumor activity by combining immune checkpoint inhibition with anti-angiogenic effects.

Mechanism of Action

Ivonescimab binds to PD-1 receptors on T cells, blocking the PD-1 pathway and thereby restoring T cell activity against tumor cells. Concurrently, it targets VEGF-A, inhibiting angiogenesis within the tumor microenvironment. This combined mechanism is intended to improve immune response and reduce tumor vascularization, potentially leading to enhanced therapeutic efficacy.

Efficacy

In a Phase 1a dose-escalation study involving 51 patients with advanced solid tumors, ivonescimab demonstrated promising antitumor activity. The confirmed objective response rate (ORR) was 25.5%, and the disease control rate (DCR) was 63.8%. Notably, responses were observed in patients with platinum-resistant ovarian cancer, endometrial cancer, microsatellite stable colorectal cancer, small cell ovarian cancer, pleural mesothelioma, and anal cancer. Among 19 patients with platinum-resistant ovarian cancer, the ORR was 26.3%, with a higher response rate at the 20 mg/kg dose level compared to 10 mg/kg (30.0% vs. 14.3%). (pmc.ncbi.nlm.nih.gov)

In a Phase II study (AK112-201), ivonescimab combined with chemotherapy was evaluated in patients with non-small cell lung cancer (NSCLC). For first-line treatment of advanced or metastatic squamous NSCLC without actionable genomic alterations, the estimated 1-year overall survival rate was 85.6%, and the 2-year overall survival rate was 64.8%. The median overall survival was not reached after a median follow-up of 21.0 months. (investor.wedbush.com)

Safety

Ivonescimab was generally well-tolerated in clinical studies. In the Phase 1a study, treatment-related adverse events (TRAEs) occurred in 74.5% of patients, with grade ≥3 TRAEs in 27.5%. The most common TRAEs included rash (29.4%), arthralgia (19.6%), hypertension (19.6%), fatigue (17.6%), and diarrhea (15.7%). Hypertension was the most common grade ≥3 TRAE (13.7%). Immune-related toxicities such as pruritus, rash, and hypothyroidism were mostly grade 1 or 2. (pmc.ncbi.nlm.nih.gov)

In the Phase II study, the frequency of TRAEs leading to discontinuation of ivonescimab was 11%, with no TRAEs resulting in patient death. The most frequent treatment-emergent adverse events were anemia, decreased neutrophil counts, and decreased white-blood cell counts. (investor.wedbush.com)

More Resources

Trial ID: NCT05899608

More trial details at ClinicalTrials.gov

Show News & AI Analysis

News and Analysis on the HARMONi-3 Clinical Trial (NCT05899608)

Industry and Media Commentary

The HARMONi-3 trial has attracted attention because it is a rare phase 3 head-to-head comparison of an investigational checkpoint inhibitor/VEGF bispecific antibody (ivonescimab, also known as AK112/XNW1011) directly against the standard-of-care regimen pembrolizumab (Keytruda) plus chemotherapy in first-line metastatic squamous non-small cell lung cancer (NSCLC) [1][2].
Multiple outlets have noted the trial's significance as one of the first to pit a next-generation PD-1/VEGF bispecific antibody directly against Keytruda in a global, multiregional first-line NSCLC setting [2].
Industry reports underline that results from HARMONi-3 are being closely watched, as they could have broad implications for the future positioning of immunotherapy and bispecific antibodies in lung cancer treatment algorithms [3].
The media and company statements emphasize that ivonescimab is designed to enhance anti-tumor immune activity while also targeting tumor angiogenesis, and that prior early-phase results in other studies have been encouraging, leading to the fast-tracking of the phase 3 trial [1].
There have been no announcements of interim clinical results, independent expert commentary on efficacy or safety, or changes to the trial protocol as of the latest available published information.

Key References

GlobeNewswire. "AKSO Announces First Patient Dosed in Phase III HARMONi-3 Trial of Ivonescimab in Combination with Chemotherapy in First-Line Squamous Non-Small Cell Lung Cancer." (July 24, 2023). Source
Fierce Biotech. "AstraZeneca partner Akso sets sights on Keytruda with head-start on global lung cancer trial, dosing first patient with PD-1/VEGF bispecific." (July 25, 2023). Source
Endpoints News. "Akso launches phase 3 study testing its PD-1/VEGF bispecific antibody in lung cancer." (July 24, 2023). Source

No interim or early results, independent expert analyses, or safety signals from HARMONi-3 have been published as of the search date.

Last updated: Apr 2025

HealthScout AI Analysis

Goal: The primary goal of the trial is to evaluate the efficacy and safety of ivonescimab combined with chemotherapy compared to pembrolizumab with chemotherapy as a first-line treatment for patients with metastatic squamous non-small cell lung cancer (NSCLC), focusing on overall survival.

Patients: The trial targets adults aged 18 and over diagnosed with metastatic squamous NSCLC, who have not received prior systemic treatment for their metastatic condition. Patients must have an ECOG performance status of 0 or 1 and a life expectancy of at least three months. Individuals with small cell lung carcinoma, non-squamous NSCLC, or known actionable genomic alterations are excluded.

Design: This is a multicenter, Phase 3 trial employing a randomized and controlled design to assess comparative outcomes across multiple regions. A total of 400 participants will be allocated to either the experimental or active comparator arm.

Treatments: The investigational treatment arm involves the administration of ivonescimab in combination with chemotherapy. Ivonescimab is a novel antibody targeting potentially multiple pathways implicated in tumor cell survival and proliferation. Previous studies have suggested its efficacy in enhancing the anti-tumor effects of chemotherapy by modulating the immune system and directly inhibiting cancer growth. In contrast, the standard treatment arm will use pembrolizumab, an established checkpoint inhibitor that has shown efficacy in prolonging survival in NSCLC by blocking the PD-1/PD-L1 pathway, thus reinvigorating immune response against cancer cells.

Outcomes: Primary endpoint: Overall Survival (OS). Secondary endpoints include Progression-Free Survival (PFS) per RECIST v1.1 criteria, and safety assessment through the incidence and severity of adverse events. The study also observes the time to any significant abnormal laboratory test results, spanning up to four years.

Burden on patient: The trial places a moderate to low burden on patients. Routine blood work and imaging follow standard protocols similar to current care regimens which typically involve periodic assessments. Travel-related commitments are expected to be manageable, with potential visits spread over extended intervals. Participation does not necessitate frequent additional procedures or high-frequency assessments beyond those integral to standard cancer care. Realistically, patients will undergo evaluations common in oncological practice, which may not significantly disrupt daily life or exceed expectations for similar Phase 3 trials.

Eligibility Criteria

Show Criteria

Sites (108)

Sort by distance to:

Clinical Study Site

Ottawa, Ontario, K1H8L6, Canada

No email / No phone

Status: Recruiting

Clinical Study Site

London, Ontario, N6A5W9, Canada

No email / No phone

Status: Recruiting

Clinical Study Site

Regina, Saskatchewan, S4T7T1, Canada

No email / No phone

Status: Recruiting

Clinical Study Site

Brest, 29200, France

No email / No phone

Status: Recruiting

Clinical Study Site

Caen, 14033, France

No email / No phone

Status: Recruiting

Clinical Study Site

Créteil, 94010, France

No email / No phone

Status: Recruiting

Clinical Study Site

Le Mans, 72000, France

No email / No phone

Status: Recruiting

Clinical Study Site

Marseille, 13915, France

No email / No phone

Status: Recruiting

Clinical Study Site

Montpellier, 34295, France

No email / No phone

Status: Recruiting

Clinical Study Site

Paris, 75000, France

No email / No phone

Status: Recruiting

Clinical Study Site

Pierre-Bénite, 69495, France

No email / No phone

Status: Recruiting

Clinical Study Site

Quimper, 29107, France

No email / No phone

Status: Recruiting

Clinical Study Site

Rennes, 35033, France

No email / No phone

Status: Recruiting

Clinical Study Site

Saint-Herblain, 44805, France

No email / No phone

Status: Recruiting

Clinical Study Site

Strasbourg, 67033, France

No email / No phone

Status: Recruiting

Clinical Study Site

Tours, 37044, France

No email / No phone

Status: Recruiting

Clinical Study Site

Villejuif, 94800, France

No email / No phone

Status: Recruiting

Clinical Study Site

Frankfurt, 60488, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Luebeck, 23538, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Kempten, 87435, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Jena, 07747, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Heidelberg, 69126, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Giesen, 35392, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Gauting, 82131, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Esslingen, 73730, Germany

No email / No phone

Status: Recruiting

Clinical Study Site

Athens, 11527, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Patra, 26443, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Patra, 26504, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Thessaloníki, 54622, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Thessaloníki, 57010, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Athens, 57010, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Athens, 15562, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Athens, 11528, Greece

No email / No phone

Status: Recruiting

Clinical Study Site

Dublin, D08 NHY1, Ireland

No email / No phone

Status: Recruiting

Clinical Study Site

Dublin, D09V2N0, Ireland

No email / No phone

Status: Recruiting

Clinical Study Site

Peschiera Del Garda, 37019, Italy

No email / No phone

Status: Recruiting

Clinical Study Site

Monterrey, 64060, Mexico

No email / No phone

Status: Recruiting

Clinical Study Site

Guadalajara, 44670, Mexico

No email / No phone

Status: Recruiting

Clinical Study Site

Monterrey, 64460, Mexico

No email / No phone

Status: Recruiting

Clinical Study Site

Monterrey, 64710, Mexico

No email / No phone

Status: Recruiting

Clinical Study Site

Łódź, 90-302, Poland

No email / No phone

Status: Recruiting

Clinical Study Site

Poznań, 60-693, Poland

No email / No phone

Status: Recruiting

Clinical Study Site

Belgrade, 11080, Serbia

No email / No phone

Status: Recruiting

Clinical Study Site

Niš, 18000, Serbia

No email / No phone

Status: Recruiting

Clinical Study Site

Belgrade, 11000, Serbia

No email / No phone

Status: Recruiting

Clinical Study Site

Kragujevac, 34000, Serbia

No email / No phone

Status: Recruiting

Clinical Study Site

Barcelona, 08035, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Badajoz, 06080, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Badalona, 08916, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Barcelona, 08003, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Barcelona, 08025, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Barcelona, 08028, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Barcelona, 08107, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Girona, 17007, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Jaén, 23007, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Lugo, 27003, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Madrid, 28040, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Madrid, 28046, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Pamplona, 31008, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Sevilla, 41013, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Valencia, 46010, Spain

No email / No phone

Status: Recruiting

Summit Therapeutics Research Center

Valencia, 46206, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

Vigo, 36312, Spain

No email / No phone

Status: Recruiting

Clinical Study Site

London, EC1A 7BE, United Kingdom

No email / No phone

Status: Recruiting

Clinical Study Site

Manchester, M20 4BX, United Kingdom

No email / No phone

Status: Recruiting

Clinical Study Site

Tucson, Arizona, 85711, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Little Rock, Arkansas, 72205, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Sacramento, California, 95817, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Los Angeles, California, 90067, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Los Angeles, California, 90033, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Santa Rosa, California, 95403, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Santa Monica, California, 90404, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Lone Tree, Colorado, 80124, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Saint Petersburg, Florida, 33705, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Plantation, Florida, 33322, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Petersburg, Florida, 33709, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Pensacola, Florida, 32503, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Pembroke Pines, Florida, 33028, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Palm Bay, Florida, 32901, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Ocala, Florida, 34474, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Jacksonville, Florida, 32256, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Fort Myers, Florida, 33901, United States

No email / No phone

Status: Recruiting

Clinical Study Site

West Palm Beach, Florida, 33401, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Lexington, Kentucky, 40503, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Burlington, Massachusetts, 01805, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Detroit, Michigan, 48202, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Ann Arbor, Michigan, 48109, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Saint Paul, Minnesota, 55101, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Billings, Montana, 59102, United States

No email / No phone

Status: Recruiting

Clinical Study Site

New York, New York, 10065, United States

No email / No phone

Status: Recruiting

Clinical Study Site

New York, New York, 10029, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Chapel Hill, North Carolina, 27514, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Charlotte, North Carolina, 28204, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Cleveland, Ohio, 44106, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Cincinnati, Ohio, 45242, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Cleveland, Ohio, 44195, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Eugene, Oregon, 97401, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Greenville, South Carolina, 29605, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Austin, Texas, 78745, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Dallas, Texas, 75246, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Tyler, Texas, 75702, United States

No email / No phone

Status: Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030, United States

[email protected] / 713-563-6096

Status: Recruiting

Clinical Study Site

Reston, Virginia, 20190, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Norfolk, Virginia, 23502, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Spokane, Washington, 99202, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Seattle, Washington, 98103, United States

No email / No phone

Status: Recruiting

Clinical Study Site

Madison, Wisconsin, 53792, United States

No email / No phone

Status: Recruiting

A Randomized, Controlled, Multiregional Phase 3 Study of Ivonescimab Combined With Chemotherapy Versus Pembrolizumab Combined With Chemotherapy for the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (HARMONi-3)

Trial Details

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: Ivonescimab (AK112/SMT112)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

More Resources

Show News & AI Analysis

News and Analysis on the HARMONi-3 Clinical Trial (NCT05899608)

Industry and Media Commentary

Key References

HealthScout AI Analysis

Eligibility Criteria

Show Criteria

Sites (108)

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site

Clinical Study Site