AK112 in Advanced Non-Small Cell Lung Cancer

NCT05499390 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: AK112-303
• Study Type: interventional
• Target: 398
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a Phase III study. All patients are stage IIIB/C (unsuitable for radical therapy) or IV 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 comparing Pembrolizumab in subjects with advanced NSCLC whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.

Conditions

Advanced Non-small-cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to 2 approximately years

Secondary Outcomes (13)

• OS

  Up to 2 approximately years

• ORR assessed by IRRC per RECIST v1.1

  Up to 2 approximately years

• DoR assessed by IRRC per RECIST v1.1

  Up to 2 approximately years

• DCR assessed by IRRC per RECIST v1.1

  Up to 2 approximately years

• TTR assessed by IRRC per RECIST v1.1

  Up to 2 approximately years

Study Arms (2)

AK112

EXPERIMENTAL

Subjects receive AK112 monotherapy intravenously (IV), selected dose.

Drug: AK112

Pembrolizumab

ACTIVE COMPARATOR

Subjects receive Pembrolizumab monotherapy intravenously (IV), 200mg q3w.

Drug: Pembrolizumab

Interventions

AK112 DRUG

Subjects receive AK112 intravenously.

AK112

Pembrolizumab DRUG

Subjects receive Pembrolizumab intravenously.

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a histologically or cytologically confirmed diagnosis of NSCLC.
• Has Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer \[AJCC\]).
• ≥18 years old (at the time consent is obtained).
• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the site study team.
• Has no EGFR-sensitive mutations or ALK gene translocations.
• Has positive PD-L1 expression in tumor tissue.
• Has no prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC.
• Has adequate organ function.
• Has recovered from the effects of any prior radiotherapy or surgery.
• All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

You may not qualify if:

• Has any histologically small cell carcinoma component.
• 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.
• Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• 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 a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator.
• 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.
• Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
• 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.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, China

Location

Related Publications (2)

• Wang L, Yao W, Shen H, Xie C, Chen H, Chen K, Su W, Gan X, Zhuo M, Chen E, Xu Z, Zhang Y, Wang M, Ma R, Wu H, Zhang Z, Ye F, Moore AC, Zhou C. Plain language summary: comparing ivonescimab with pembrolizumab in people with PD-L1-positive non-small cell lung cancer in the HARMONi-2 study. Future Oncol. 2026 Jan;22(1):27-36. doi: 10.1080/14796694.2025.2601138. Epub 2025 Dec 28.

  PMID: 41457351 DERIVED

• Xiong A, Wang L, Chen J, Wu L, Liu B, Yao J, Zhong H, Li J, Cheng Y, Sun Y, Ge H, Yao J, Shi Q, Zhou M, Chen B, Han Z, Wang J, Bu Q, Zhao Y, Chen J, Nie L, Li G, Li X, Yu X, Ji Y, Sun D, Ai X, Chu Q, Lin Y, Hao J, Huang D, Zhou C, Shan J, Yang H, Liu X, Wang J, Shang Y, Mei X, Yang J, Lu D, Hu M, Wang ZM, Li B, Xia M, Zhou C. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025 Mar 8;405(10481):839-849. doi: 10.1016/S0140-6736(24)02722-3.

  PMID: 40057343 DERIVED

MeSH Terms

Interventions

pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 12, 2022
• Study Start: November 9, 2022
• Primary Completion: January 29, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)