Advanced Squamous Non Small Cell Lung CancerPhase 3NCT05840016
AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer
A Phase 3 study testing AK112, Carboplatin, Paxlitaxel and Tislelizumab, Carboplatin, Paxlitaxel in people with Advanced Squamous Non Small Cell Lung Cancer, run by Akeso at 1 site in China.
Trial summary
This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or stage IV squamous non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Squamous Non Small Cell Lung Cancer
- What is being tested?
- AK112, Carboplatin, Paxlitaxel and Tislelizumab, Carboplatin, Paxlitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 532 participants
- Where
- 1 siteChina
- Study dates
- 17 Aug 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- ≥18 years old and ≤75 years old (at the time consent is obtained).
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Has a life expectancy of at least 3 months.
- Has a histologically confirmed diagnosis of squamous NSCLC.
- Has Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC]).
Show all 9Show fewer
- Has no prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
- Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Has adequate organ function.
Who cannot join
- Histological diagnosis of non-squamous NSCLC.
- Has EGFR-sensitive mutations or ALK gene translocations.
- Known ROS1 rearrangement, MET exon 14 skipping mutation, or RET gene fusion positivite.
- Is currently participating in a study of an investigational agent or using an investigational device.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment.
- Has undergone major surgery within 30 days of Study Day 1.
Show all 14Show fewer
- Has known active central nervous system (CNS) metastases.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Has an active infection requiring systemic therapy.
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- History of myocardial infarction, unstable angina, congestive heart failure within 12 months prior to day 1 of study treatment.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Has received a live virus vaccine within 30 days of the planned first dose of study therapy.
- Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Combined With Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer
This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or stage IV squamous non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with chemotherapy versus Tislelizumab combined with chemotherapy in patients with advanced squamous NSCLC.
- Being tested
- AK112, Carboplatin, Paxlitaxel, Tislelizumab, Carboplatin, Paxlitaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK112, Carboplatin, PaxlitaxelDrug
IV infusion,Specified dose on specified days
Tislelizumab, Carboplatin, PaxlitaxelDrug
IV infusion,Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Experimental: AK112 in Combination With Paclitaxel Plus Carboplatin | Experimental | AK112 will be administered at a selected dose intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. Receives: Drug: AK112, Carboplatin, Paxlitaxel |
| Active Comparator: Tislelizumab in Combination With Paclitaxel Plus Carboplatin | Active comparator | Tislelizumab will be administered at a dose of 200 mg intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. Receives: Drug: Tislelizumab, Carboplatin, Paxlitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS assessed by IRRC per RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the blinded IRRC or death due to any cause (whichever occurs first).
Measured: Up to approximately 2 years
Secondary outcomes (14)
OS
Overall Survival (OS) is defined as the time from the start of treatment with AK112 until death due to any cause.
Measured: Up to approximately 2 years
ORR assessed by IRRC per RECIST v1.1
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.
Measured: Up to approximately 2 years
DoR assessed by IRRC per RECIST v1.1
Duration of response (DoR) assessed according to RECIST v1.1
Measured: Up to approximately 2 years
DCR assessed by IRRC per RECIST v1.1
Disease control rate (DCR) assessed according to RECIST v1.1.
Measured: Up to approximately 2 years
TTR assessed by IRRC per RECIST v1.1
Time to response (TTR) is defined as the time to response base on RECIST v1.1.
Measured: Up to approximately 2 years
PFS assessed by investigator per RECIST v1.1
Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression assessed by the investigator or death due to any cause (whichever occurs first).
Measured: Up to approximately 2 years
ORR assessed by the investigator per RECIST v1.1
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1.
Measured: Up to approximately 2 years
DoR assessed by the investigator per RECIST v1.1
Duration of response (DoR) assessed according to RECIST v1.1.
Measured: Up to approximately 2 years
DCR assessed by the investigator per RECIST v1.1
Disease control rate (DCR) assessed according to RECIST v1.1.
Measured: Up to approximately 2 years
TTR assessed by the investigator per RECIST v1.1
Time to response (TTR) is defined as the time to response base on RECIST v1.1.
Measured: Up to approximately 2 years
AE
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measured: Up to approximately 2 years
ADA
Number of subjects with detectable anti-drug antibodies (ADA).
Measured: Up to approximately 2 years
Cmax and Cmin
AK112 serum drug concentrations in subjects at different time points after AK112 administration
Measured: Up to approximately 2 years
PD-L1 expression
The correlationship between PD-L1 expression and efficacy.
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2023
- Study start17 Aug 2023
- Primary completion28 Feb 2025
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Squamous Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AkesoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 532 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05840016
- Sponsor's protocol ID
- AK112-306
- Status last verified
- Apr 2025
- First submitted
- 21 Apr 2023
- Last updated
- 2 May 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen Z, Yang F, Jiang Z, Sun L, Wu L, Han Z, Fan Y, Zhao Y, Li X, Xu H, Meng X, Liu Y, Zhang Z, Luo H, Ma X, Ma X, Shi Q, Zhang Z, Yang R, Wang P, Pan P, Ai X, Li J, Pu X, Wang Z, Fang J, He M, He Y, Guo S, Li J, Wang H, Zhang J, Chu Q, Liu X, Ying S, Wu H, Sun H, Ji Y, Zhou M, Cao C, Tang K, Li Z, Li D, Zhang Z, Li J, Zhou J, Yang H, Du Y, Yang H, Shi J, Chen H, Moore AC, Lu S. Plain language summary: comparing ivonescimab plus chemotherapy with tislelizumab plus chemotherapy in people with advanced squamous non-small cell lung cancer in the HARMONi-6 study. Future Oncol. 2026 Jun;22(14):1637-1650. doi: 10.1080/14796694.2026.2676052. Epub 2026 Jun 3.
PubMed 42233228Lu S, Liu B, Luo Y, Sun L, Wu L, Han Z, Fan Y, Zhao Y, Li X, Xu H, Meng X, Liu Y, Zhang Z, Luo H, Ma X, Ma X, Shi Q, Zhang Z, Yang R, Wang P, Pan P, Ai X, Li J, Pu X, Wang Z, Fang J, He M, He Y, Guo S, Li J, Wang H, Zhang J, Chu Q, Liu X, Ying S, Wu H, Sun H, Ji Y, Zhou M, Cao C, Tang K, Li Z, Li D, Zhang Z, Li J, Zhou J, Yang H, Du Y, Yang H, Shi J, Chen H, Chen Z, Li W, Lu D, Hu M, Wang ZM, Li B, Xia MY. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China. Lancet. 2026 Jun 27;407(10548):2620-2629. doi: 10.1016/S0140-6736(26)00966-9. Epub 2026 May 31.
PubMed 42218899
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Combined With Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05840016
- Acronym / sponsor ID
- AK112-306
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 532 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Study start
- 17 Aug 2023 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 3 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or stage IV squamous non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with chemotherapy versus Tislelizumab combined with chemotherapy in patients with advanced squamous NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: AK112 in Combination With Paclitaxel Plus Carboplatin | Experimental | Drug: AK112, Carboplatin, PaxlitaxelAK112 will be administered at a selected dose intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. |
| Active Comparator: Tislelizumab in Combination With Paclitaxel Plus Carboplatin | Active comparator | Drug: Tislelizumab, Carboplatin, PaxlitaxelTislelizumab will be administered at a dose of 200 mg intravenously (IV) every three weeks (Q3W). Carboplatin will be administered at AUC5, Q3W, intravenously (IV) for 4 cycles. Paclitaxel will be administered at 175 mg/m2, Q3W, intravenously (IV) for 4 cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
- ≥18 years old and ≤75 years old (at the time consent is obtained).
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Has a life expectancy of at least 3 months.
- Has a histologically confirmed diagnosis of squamous NSCLC.
Key exclusion criteria (14 listed)
- Histological diagnosis of non-squamous NSCLC.
- Has EGFR-sensitive mutations or ALK gene translocations.
- Known ROS1 rearrangement, MET exon 14 skipping mutation, or RET gene fusion positivite.
- Is currently participating in a study of an investigational agent or using an investigational device.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK112, Carboplatin, PaxlitaxelIV infusion,Specified dose on specified days | Drug | Experimental: AK112 in Combination With Paclitaxel Plus Carboplatin |
| Tislelizumab, Carboplatin, PaxlitaxelIV infusion,Specified dose on specified days | Drug | Active Comparator: Tislelizumab in Combination With Paclitaxel Plus Carboplatin |
Primary outcome
PFS assessed by IRRC per RECIST v1.1
Time frame: Up to approximately 2 years
Progression-free survival (PFS) is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the blinded IRRC or death due to any cause (whichever occurs first).
14 secondary outcomes
OS
Time frame: Up to approximately 2 years
ORR assessed by IRRC per RECIST v1.1
Time frame: Up to approximately 2 years
DoR assessed by IRRC per RECIST v1.1
Time frame: Up to approximately 2 years
DCR assessed by IRRC per RECIST v1.1
Time frame: Up to approximately 2 years
TTR assessed by IRRC per RECIST v1.1
Time frame: Up to approximately 2 years
PFS assessed by investigator per RECIST v1.1
Time frame: Up to approximately 2 years
ORR assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
DoR assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
DCR assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
TTR assessed by the investigator per RECIST v1.1
Time frame: Up to approximately 2 years
AE
Time frame: Up to approximately 2 years
ADA
Time frame: Up to approximately 2 years
Cmax and Cmin
Time frame: Up to approximately 2 years
PD-L1 expression
Time frame: Up to approximately 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Derived from this study: PubMed 42233228Chen Z, Yang F, Jiang Z, Sun L, Wu L, Han Z, Fan Y, Zhao Y, Li X, Xu H, Meng X, Liu Y, Zhang Z, Luo H, Ma X, Ma X, Shi Q, Zhang Z, Yang R, Wang P, Pan P, Ai X, Li J, Pu X, Wang Z, Fang J, He M, He Y, Guo S, Li J, Wang H, Zhang J, Chu Q, Liu X, Ying S, Wu H, Sun H, Ji Y, Zhou M, Cao C, Tang K, Li Z, Li D, Zhang Z, Li J, Zhou J, Yang H, Du Y, Yang H, Shi J, Chen H, Moore AC, Lu S. Plain language summary: comparing ivonescimab plus chemotherapy with tislelizumab plus chemotherapy in people with advanced squamous non-small cell lung cancer in the HARMONi-6 study. Future Oncol. 2026 Jun;22(14):1637-1650. doi: 10.1080/14796694.2026.2676052. Epub 2026 Jun 3.
- Derived from this study: PubMed 42218899Lu S, Liu B, Luo Y, Sun L, Wu L, Han Z, Fan Y, Zhao Y, Li X, Xu H, Meng X, Liu Y, Zhang Z, Luo H, Ma X, Ma X, Shi Q, Zhang Z, Yang R, Wang P, Pan P, Ai X, Li J, Pu X, Wang Z, Fang J, He M, He Y, Guo S, Li J, Wang H, Zhang J, Chu Q, Liu X, Ying S, Wu H, Sun H, Ji Y, Zhou M, Cao C, Tang K, Li Z, Li D, Zhang Z, Li J, Zhou J, Yang H, Du Y, Yang H, Shi J, Chen H, Chen Z, Li W, Lu D, Hu M, Wang ZM, Li B, Xia MY. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China. Lancet. 2026 Jun 27;407(10548):2620-2629. doi: 10.1016/S0140-6736(26)00966-9. Epub 2026 May 31.
Related trials for Advanced Squamous Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Not yet recruitingPhase 2
Phase II Study to Evaluate Telisotuzumab Adizutecan in Combination With RC148(ABBV-1480) as First-Line Treatment for Patients With Non-Squamous Non-Small-Cell Lung Cancer
Patients With Locally Advanced or Metastatic Non-Squamous NSCLC Requiring First-Line Treatment and no Driver Gene Alterations Confirmed by Histology or Cytology
Active, not recruitingPhase 2
Carboplatin, Taxane And Ramucirumab for Patients With NSCLC After Pemetrexed or Pembrolizumab Maintenance
Non-small Cell Lung Cancer
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AK112, Carboplatin, Paxlitaxel and Tislelizumab, Carboplatin, Paxlitaxel in people with Advanced 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 9 inclusion and 14 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 2 May 2025. 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. 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?
PFS assessed by IRRC per RECIST v1.1 (time frame: Up to approximately 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 NCT05840016, 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 2 May 2025.