Phase 3 Clinical Study of AK112 for NSCLC Patients

NCT ID: NCT05184712

Last Updated: 2024-06-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 322 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-25
• Study Completion Date: 2025-11-02

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

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.

Conditions

Non-Squamous Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Ivonescimab (SMT112 or AK112) Injection

Intervention Type: 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.

Placebo in combination with Pemetrexed and 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.

Group Type: PLACEBO_COMPARATOR

Placebo Injection

Intervention Type: 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.

Interventions

Ivonescimab (SMT112 or AK112) Injection

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.

Intervention Type: DRUG

Placebo Injection

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.

Intervention Type: DRUG

Other Intervention Names

Pemetrexed; Carboplatin; Pemetrexed; Carboplatin

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

4. Life expectancy ≥3 months；

5. 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;

6. The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment

7. Have previously received EGFR-TKI treatment and the treatment has failed

8. Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1

9. Major organ function prior to treatment meets the following criteria

10. Patients of childbearing potential must agree to use effective contraceptive measures

Exclusion Criteria

1. Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma

2. There are reports confirming the existence of other driver gene mutations with known drug treatments

3. Subjects who received any prior treatments targeting the mechanism of tumor immunity

4. The subject has received systemic anti-tumor therapy other than EGFR-TKI

5. Currently enrolled in any other clinical study

6. 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.

7. Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.

8. Symptomatic central nervous system metastases

9. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors

10. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment

11. There is a history of major diseases 1 year prior to the first dose.

12. .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose

13. Received chest radiation therapy prior to the first dose

14. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.

15. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 38820549 (View on PubMed)

Other Identifiers

HARMONi-A

Identifier Type: OTHER

Identifier Source: secondary_id

AK112-301

Identifier Type: -

Identifier Source: org_study_id