Phase 3 Clinical Study of AK112 for NSCLC Patients

NCT05184712 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: AK112-301HARMONi-A
• Study Type: interventional
• Target: 322
• Locations: 1 country
• Sites: 1

Brief 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) Treatment

Conditions

Non-Squamous Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

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

  Up to 2 years

Secondary Outcomes (9)

• OS

  Up to 2 years

• ORR

  Up to 2 years

• DCR

  Up to 2 years

• DoR

  Up to 2 years

• TTR

  Up to 2 years

Study Arms (2)

Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin

EXPERIMENTAL

Subjects 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.

Drug: Ivonescimab (SMT112 or AK112) Injection

Placebo in combination with Pemetrexed and Carboplatin

PLACEBO COMPARATOR

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.

Drug: Placebo Injection

Interventions

Ivonescimab (SMT112 or AK112) Injection DRUG

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.

Also known as: Pemetrexed, Carboplatin

Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin

Placebo Injection DRUG

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.

Also known as: Pemetrexed, Carboplatin

Placebo in combination with Pemetrexed and Carboplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

Related Publications (1)

• 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.

  PMID: 38820549 DERIVED

MeSH Terms

Interventions

Injections; Pemetrexed; Carboplatin

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Li Zhang, MD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

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: December 21, 2021
• First Posted: January 11, 2022
• Study Start: January 25, 2022
• Primary Completion: March 10, 2023
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

CN (1)