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Non-Squamous Non-small Cell Lung CancerPhase 3NCT05184712

Phase 3 Clinical Study of AK112 for NSCLC Patients

A Phase 3 study testing Ivonescimab (SMT112 or AK112) Injection in people with Non-Squamous Non-small Cell Lung Cancer, run by Akeso at 1 site in China.

Active, not recruiting

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

Official record
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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 Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non-Squamous Non-small Cell Lung Cancer
What is being tested?
Ivonescimab (SMT112 or AK112) Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
322 participants
Where
1 siteChina
Study dates
25 Jan 2022to Sep 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 to 75 years
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  • Life expectancy ≥3 months；
  • Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
  • The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
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  • Have previously received EGFR-TKI treatment and the treatment has failed
  • Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
  • Major organ function prior to treatment meets the following criteria
  • Patients of childbearing potential must agree to use effective contraceptive measures

Who cannot join

  • Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
  • There are reports confirming the existence of other driver gene mutations with known drug treatments
  • Subjects who received any prior treatments targeting the mechanism of tumor immunity
  • The subject has received systemic anti-tumor therapy other than EGFR-TKI
  • Currently enrolled in any other clinical study
  • Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 weeks prior to the first dose.
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  • Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
  • Symptomatic central nervous system metastases
  • Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
  • Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
  • There is a history of major diseases 1 year prior to the first dose.
  • .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
  • Received chest radiation therapy prior to the first dose
  • Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
  • Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510000

Other trials in China

About this study

Official title: A Randomized, Double-blind, Multi-center, Phase III Study of AK112 Combined With Pemetrexed and Carboplatin Versus Placebo Combined With Pemetrexed and Carboplatin in Patients With Locally Advanced or Metastatic EGFR-mutant Non-squamous NSCLC Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs)

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 Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

Read the detailed description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare 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 320 subjects will be randomized to the two treatment at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the AK112/Placebo Plus Pemetrexed and Carboplatin （Q3W,up to 4 cycles）in treatment periods per the randomization schedule. Afterward, AK112/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Being tested
Ivonescimab (SMT112 or AK112) Injection, Placebo Injection

What participants receive

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

  • Ivonescimab (SMT112 or AK112) InjectionDrug

    Also called Pemetrexed, Carboplatin

    Subjects will receive Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, Ivonescimab (SMT112 or 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 NCT05184712
Study groupRoleWhat they receive
Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and CarboplatinExperimentalSubjects will receive Ivonescimab (SMT112 or 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: Ivonescimab (SMT112 or AK112) Injection
Placebo in combination with Pemetrexed and CarboplatinPlacebo 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

Secondary outcomes (9)

  1. OS

    Overall Survival (OS) in the ITT population

    Measured: Up to 2 years

  2. ORR

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

    Measured: Up to 2 years

  3. DCR

    Disease control rate (DCR), which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1

    Measured: Up to 2 years

  4. DoR

    Duration of response (DoR), which is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

    Measured: Up to 2 years

  5. TTR

    TTR is defined as the time to response base on RECIST v1.1

    Measured: Up to 2 years

  6. PFS

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1.

    Measured: Up to 2 years

  7. 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

  8. 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 year

  9. 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

Timeline

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

  1. First posted11 Jan 2022
  2. Study start25 Jan 2022
  3. Primary completion10 Mar 2023
  4. Study completionSep 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
322 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05184712
Sponsor's protocol ID
AK112-301
Other IDs
HARMONi-A
Status last verified
Mar 2026
First submitted
21 Dec 2021
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Sun L, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Shi M, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Liu Y, Chen L, Hou X, Zhang Y, Guo J, Ma R, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Xia M, Lu D, Hu M, Wang ZM, Li B, Xia MY, Zhang L. Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial. JAMA. 2026 Jul 28;336(4):306-314. doi: 10.1001/jama.2026.7745.

    PubMed 42307937

  • HARMONi-A Study Investigators; Fang W, Zhao Y, Luo Y, Yang R, Huang Y, He Z, Zhao H, Li M, Li K, Song Q, Du X, Sun Y, Li W, Xu F, Wang Z, Yang K, Fan Y, Liu B, Zhao H, Hu Y, Jia L, Xu S, Yi T, Lv D, Lan H, Li M, Liang W, Wang Y, Yang H, Jia Y, Chen Y, Lu J, Feng J, Liu C, Zhou M, Zhou J, Liu X, Zhou N, He M, Dong X, Chen H, Chen Y, Su H, Li X, Zhang Z, Yang L, Cheng Y, Chen L, Hou X, Zhang Y, Guo J, Wang Z, Lu H, Wu D, Feng W, Li W, Huang J, Wang Y, Song X, Peng J, Liu L, Guo Y, Li W, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhang L. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. 2024 Aug 20;332(7):561-570. doi: 10.1001/jama.2024.10613.

    PubMed 38820549

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ivonescimab (SMT112 or AK112) Injection in people with Non-Squamous Non-small Cell Lung Cancer, run by Akeso at 1 site in China.

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 10 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 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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. Some participants in this study may receive a placebo. 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). 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 NCT05184712, which also lists 2 linked publications.

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 4 Mar 2026.

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