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Non-Squamous Non-small Cell Lung CancerPhase 3NCT06396065

Phase III Study of AK112 for NSCLC Patients

A Phase 3 study testing AK112 Injection in people with Non-Squamous Non-small Cell Lung Cancer, run by Summit Therapeutics at 74 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Squamous Non-small Cell Lung Cancer
What is being tested?
AK112 Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
420 participants
Where
74 sitesin 6 countries
Study dates
4 May 2023to 31 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
  • Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent. (For patients from North America and Europe, there will be no upper age cutoff)
  • ECOG performance status score of 0 or 1.
  • Expected survival ≥3 months.
  • Histologically or cytology-confirmed, locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC (according to TNM staging of lung cancer, 8th edition) that cannot be completely resected by surgery and cannot receive radical concurrent/sequential chemoradiation.
  • EGFR activation mutations that are confirmed by tumor histology or cytology or blood test before enrollment (eg, exon 18 point mutations, exon 19 deletions, exon 20 point mutations, and exon 21 point mutations). Patients must provide a previous EGFR mutation test report, otherwise tumor tissue samples, peripheral blood samples, or pleural fluid samples will need to be collected for EGFR status testing prior to enrollment.
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  • Prior treatment with EGFR TKI and treatment failure, meeting any of the following requirements: Progression after treatment with first- or second-generation EGFR TKI, and confirmation of absence of T790M mutation after progression (only for patients enrolled in China). Progression after treatment with a third-generation EGFR TKI (eg, osimertinib, ametinib, vometinib). Note, for North America and Europe patients only.
  • According to RECIST v1.1, there is at least 1 measurable noncerebral lesion.
  • Adequate organ function determined by the following requirements
  • Female patients of childbearing age have a negative serum pregnancy test result within 3 days before the first dose
  • If a female patient of childbearing potential has sex with an unsterilized male partner, the patient must use a highly effective method of contraception from the beginning of screening and must agree to continue using these precautions until 120 days after the last dose of the study drug or until 6 months after the last carboplatin and pemetrexed dose (whichever is longer).
  • If an unsterilized male patient has sex with a female partner of childbearing potential, the patient must use an effective method of contraception from the beginning of screening to day 120 after the last dose or until 6 months after the last carboplatin and pemetrexed dose (whichever is longer). The decision to stop contraception after this time point should be discussed with investigator.

Who cannot join

  • Histologic or cytopathologic evidence of the presence of a small cell carcinoma component, or a predominantly squamous cell carcinoma.
  • Patients who have received immune checkpoint inhibitors (eg, anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.)
  • Received prior systemic chemotherapy, anti-angiogenic therapy, or more than one prior line of antitumor therapy (other than EGFR inhibitors) for advanced stage (IIIB to IV) NSCLC.
  • Concurrent enrollment in another clinical study, unless it is a noninterventional clinical study or the follow-up period of the interventional study is more than 4 weeks from the last dose of the prior clinical study or more than 5 half-lives of the prior study drug, whichever is shorter.
  • Received EGFR inhibitor therapy within 2 weeks (with the exception of osimertinib to be within 7 days) prior to the first dose; received nonspecific immunomodulatory therapy (eg, interleukin, interferon, thymus peptide, tumor necrosis factor) within 2 weeks prior to the first dose, excluding IL-11 for the treatment of thrombocytopenia; have received Chinese herbal medicines or proprietary Chinese medicines with antitumor indications within 1 week before the first dose.
  • Imaging during the screening period shows that the tumor surrounds important blood vessels or has obvious necrosis and/or cavitation of tumor lesions within the lung parenchyma.
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  • Imaging during the screening period shows that the tumor invades the surrounding vital organs and blood vessels, such as the heart and pericardium, trachea, esophagus, aorta, superior vena cava, or patient is at risk of esophageal tracheal fistula or esophageal pleural fistula.
  • Symptomatic metastases of the central nervous system.
  • Malignant tumors other than NSCLC within 3 years before the first dose.
  • Active autoimmune disease requiring systemic therapy (eg, with disease-modifying drugs, corticosteroids, immunosuppressant therapy) within 2 years prior to the first dose (excluding ir AEs due to PD-1/L1 inhibitors). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent) for adrenal or pituitary insufficiency) is permitted.
  • There is a history of major diseases before the first dose
  • History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea) within 6 months before the first study drug administration.
  • Patients with >30 Gy of chest radiation therapy within 6 months prior to the first dose, nonthoracic radiation therapy >30 Gy within 4 weeks prior to the first dose, and palliative radiation therapy of ≤30 Gy within 2 weeks prior to the first dose and failed to recover from the toxicity and/or complications of these interventions to NCI CTCAE Grade ≤1 (except hair loss and fatigue). Palliative radiotherapy for symptom control is permitted if it has been completed at least 2 weeks before the first dose, and no additional radiotherapy for the same lesion is planned.
  • Inactivated vaccines are allowed. Patients are excluded if they have received a live vaccine or live attenuated vaccine within 4 weeks prior to the first dose, or if they are scheduled to receive a live vaccine or live attenuated vaccine during the study period.
  • Severe infection within 4 weeks prior to the first dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection that has received systemic anti-infective therapy within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or C)

Trial locations and contacts

74 sites in 6 countries.

74 sites in 6 countries

United States43 sites

  • Texas Oncology South Austin

    Austin, Texas, 78745

  • CBCC Global Research

    Bakersfield, California, 93309

  • Hematology/Oncology Clinic - SCRI

    Baton Rouge, Louisiana, 70809

  • American Oncology Partners

    Bethesda, Maryland, 20817

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Medical University South Carolina

    Charleston, South Carolina, 29425

  • New York Oncology/Hematology

    Clifton Park, New York, 12065

  • Zangmeister Cancer Center

    Columbus, Ohio, 43219

  • Texas Oncology Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Williamette Valley Cancer Institute and Research

    Eugene, Oregon, 97401

  • Virginia Cancer specialisits

    Fairfax, Virginia, 22031

  • Oncology Hematology Care

    Fairfield, Ohio, 45014

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58102

  • The Oncology Institute of Hope & Innovation

    Fort Lauderdale, Florida, 33308

  • MD Anderson University of Texas

    Houston, Texas, 77030

  • UC San Diego

    La Jolla, California, 92093

  • Rocky Mountain Cancer Center

    Lone Tree, Colorado, 80124

  • University of Southern California

    Los Angeles, California, 90033

  • Valkyrie Clinical Trials

    Los Angeles, California, 90067

  • UCLA Department of Medicine - Hematology/Oncology

    Los Angeles, California, 90095

  • Baptist Hospital

    Memphis, Tennessee, 38120

  • University of Miami

    Miami, Florida, 33136

  • Palo Alto Medical Foundation Research Institute

    Mountain View, California, 94040

  • NYU Langone Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Mount Sinai

    New York, New York, 10029

  • Florida Cancer Associates - Ocala Oncology

    Ocala, Florida, 34474

  • Providence St. Joseph

    Orange, California, 92868

  • UC Irvine

    Orange, California, 92868

  • BRCR Global

    Plantation, Florida, 33322

  • Kaiser Permanente Northwest

    Portland, Oregon, 97227

  • Sutter Cancer center

    Sacramento, California, 95816

  • UC DAVIS Comprehensive Cancer Center

    Sacramento, California, 95817

  • HealthPartners Cancer Research Center

    Saint Paul, Minnesota, 55101

  • Sharp Memorial Hospital

    San Diego, California, 92123

  • California Pacific Medical Center

    San Francisco, California, 94115

  • Providence Medical Foundation

    Santa Rosa, California, 95403

  • New England Cancer Specialists

    Scarborough, Maine, 04074

  • Florida Cancer Specialists - North

    St. Petersburg, Florida, 33705

  • BRCR Global

    Tamarac, Florida, 33321

  • Compass Oncology

    Vancouver, Washington, 98684

  • Texas Oncology Webster

    Webster, Texas, 77598

  • Florida Cancer Specialists -East

    West Palm Beach, Florida, 33401

  • Presbyterian Intercommunity Hospital

    Whittier, California, 90602

Other trials in United States

Spain13 sites

  • Hospital Teresa Herrera

    A Coruña, 15006

  • Vall d'Hebron Institute of Oncology

    Barcelona, 08035

  • Badalona-Hospital Germans Trias i Pujol

    Barcelona, 08916

  • omplejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria

    Las Palmas, 35016

  • Lucus Augusti University Hospital

    Lugo, 27002

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario Clinico San Carlos

    Madrid, 28040

  • Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario La Paz

    Madrid, 28046

  • Puerta de Hierro University Hospital

    Majadahonda, 28222

  • Hospital Regional Universitario de Malaga

    Málaga, 29011

  • Hospital Universitario Nuestro Senora de Valme

    Seville, 41014

Other trials in Spain

Canada6 sites

  • Cross cancer Institute

    Edmonton, Alberta, T6g 1Z2

  • Lung Cancer Canada

    Ottawa, Ontario, K1H 8L6

  • Universite Hospital Laval

    Québec, G1V 4G5

  • Allan Blaire Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5g 2M9

  • BC Cancer

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

France5 sites

  • CHI Creteil

    Créteil, 94010

  • Léon Bérard Cancer Center, Lyon

    Lyon, 69008

  • Hospital Bichat-Claude Bernard

    Paris, 75018

  • Institut Curie

    Paris, 75248

  • Gustave Roussy Cancer

    Villejuif, 94800

Other trials in France

Italy5 sites

  • Istituto Nazionale dei Tumori

    Milan, 20133

  • Instituto Europeo di Oncologia

    Milan, 20141

  • University Hospital of Parma

    Parma, 43126

  • Campus Bio-Medico University

    Roma, 00128

  • Istituto Nazionale Tumori, Regina Elena

    Rome, 00144

Other trials in Italy

United Kingdom2 sites

  • The Royal Marsden

    London, SW3 6JJ

  • The Christie NHS Foundation Trust

    Manchester, M20 4GJ

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (HARMONi)

Read the detailed description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare Ivonescimab (SMT112 /AK112) Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 420 subjects will be randomized to two treatment arms at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the Ivonescimab (SMT112 /AK112)/Placebo Plus Pemetrexed and Carboplatin (Q3W,up to 4 cycles) in treatment periods per the randomization schedule. Afterward, Ivonescimab (SMT112 /AK112)/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Being tested
AK112 Injection, Placebo Injection
Keywords
NSCLC, EGFR Positive, ivonescimab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AK112 InjectionDrug

    Also called Pemetrexed, Carboplatin

    Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

  • Placebo InjectionDrug

    Also called Pemetrexed, Carboplatin

    Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Study groups in NCT06396065
Study groupRoleWhat they receive
AK112 in combination with Pemetrexed and CarboplatinExperimentalSubjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
Receives: Drug: AK112 Injection
Placebo in combination with Pemetrexed and CarboplatinActive comparatorSubjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
Receives: Drug: Placebo Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS)

    Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.

    Measured: Up to 2 years

  2. Overall Survival (OS) in the ITT population

    Overall Survival (OS) in the ITT population

    Measured: Up to 2 years

Secondary outcomes (5)

  1. ORR

    Efficacy measures such as overall response rate (ORR) and duration of response (DoR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1

    Measured: Up to 2 years

  2. AE

    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.

    Measured: From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first,up to 2 years

  3. Observed concentrations of AK112

    The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration

    Measured: through study completion, an average of 2 years

  4. Number of subjects who develop detectable anti-drug antibodies (ADAs)

    The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs)

    Measured: From first dose of AK112 through 90 days after last dose of AK112, up to 2 years

  5. DoR

    Duration of response (DoR) which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2024
  2. Study start4 May 2023
  3. Primary completion12 Apr 2025
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
420 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06396065
Sponsor's protocol ID
AK112-301 (HARMONi)
Status last verified
Jul 2026
First submitted
25 Apr 2024
Last updated
28 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Le X, Passaro A, Zhao Y, Huang Y, Laskin J, Rodriguez-Abreu D, Calles A, Bazhenova L, Lo Russo G, Leighl NB, Cappuzzo F, Girard N, Popat S, Fang W, Luo Y, Li W, He Z, Zhao H, Li M, Song Q, Zhao H, El Darsa H, Monnet I, Cobo Dols M, Garcia Campelo R, Jotte R, Berz D, Spira A, Perol M, Nagasaka M, West H, Styles L, Li J, Clow F, Goldman J, Zhang L. Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2026 Sep;27(9):1094-1109. doi: 10.1016/S1470-2045(26)00282-2.

    PubMed 42636833

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AK112 Injection in people with Non-Squamous Non-small Cell Lung Cancer, run by Summit Therapeutics at 74 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 sites in United States, Spain, Canada, France, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06396065, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.

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