Phase 3 Clinical Study of AK112 for NSCLC Patients

A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of Ivonescimab (SMT112 or AK112) or Placebo Plus Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (HARMONi)

Study Overview

• Status: Recruiting
• Conditions: Non-Squamous Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Placebo Injection; Drug: Ivonescimab (SMT112 or AK112) Injection

Detailed Description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare Ivonescimab (SMT112 or 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 470 subjects will be randomized to two treatment arms at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin or Placebo Plus Pemetrexed and Carboplatin（Q3W, up to 4 cycles) in treatment periods per the randomization schedule. Afterward, Ivonescimab (SMT112 or AK112) Plus Pemetrexed or Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 470
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lori Styles, MD; Phone Number: 1-833-256-0522; Email: medicalinformation@smmttx.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 172
      • Recruiting
      • Cross Cancer Institute, University of Alberta, Edmonton AB
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L3
      • Recruiting
      • BC Cancer
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, H5G 2M9
      • Recruiting
      • Princess Margaret Cancer Center
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Recruiting
      • Hospital Laval
  • Saskatchewan
    • Regina, Saskatchewan, Canada
      • Recruiting
      • Allan Blair Cancer Center
• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Li Zhang, Master; Phone Number: 139 0228 2893
• France
  • Créteil, France
    • Recruiting
    • Service de Pneumologie, CHI Créteil
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat-Claude Bernard
  • Paris, France
    • Recruiting
    • Institut Curie
• Italy
  • Roma, Italy
    • Recruiting
    • Campus Bio-Medico University
• Spain
  • Barcelona, Spain
    • Recruiting
    • Vall d'Hebron Institute of Oncology
  • Barcelona, Spain
    • Recruiting
    • Badalona-Hospital Germans Trias i Pujol
  • Barcelona, Spain
    • Recruiting
    • Institutes Català d'Oncologia, Badalona-Hospital Germans Trias i Pujol
  • Coruña, Spain
    • Recruiting
    • Hospital Teresa Herrera
  • Las Palmas, Spain
    • Recruiting
    • Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria
  • Lugo, Spain
    • Recruiting
    • Lucus Augusti University Hospital
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Recruiting
    • Instituto de Investigación Sanitaria-Fundación Jiménez Díaz
  • Majadahonda, Spain
    • Recruiting
    • Puerta de Hierro University Hospital, Majadahonda
  • Málaga, Spain
    • Recruiting
    • Hospital Regional Universitario de Malaga
  • San Carlos, Spain
    • Recruiting
    • Hospital Universitario Clinico San Carlos
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Nuestra Señora de Valme
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Recruiting
      • CBCC Global Research Inc. at Comprehensive Blood and Cancer Center
    • La Jolla, California, United States, 92093
      • Recruiting
      • UC San Diego
    • Los Altos, California, United States, 94022
      • Recruiting
      • Palo Alto Medical Foundation Research Institute
    • Los Angeles, California, United States, 90067
      • Recruiting
      • Valkyrie Clinical Trials
    • Los Angeles, California, United States, 90007
      • Recruiting
      • University of Southern California
    • Los Angeles, California, United States, 90024
      • Recruiting
      • UCLA Jonsson Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • Recruiting
      • UC Irvine
    • Orange, California, United States, 92868
      • Recruiting
      • Hematology-Oncology Medical Group of Orange County, Inc
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95816
      • Recruiting
      • Sutter Cancer Center
    • San Francisco, California, United States, 94110
      • Recruiting
      • California Pacific Medical Center
    • Santa Rosa, California, United States, 95405
      • Recruiting
      • Providence Medical Foundation
    • Whittier, California, United States, 90602
      • Recruiting
      • Presbyterian Intercommunity Hospital (PIH)
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Recruiting
      • Rocky Mountain Cancer Centers, LLP
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
    • Ocala, Florida, United States, 34474
      • Recruiting
      • Florida Cancer Associates-Ocala Oncology
    • Plantation, Florida, United States, 33322
      • Recruiting
      • BRCR Global
    • Saint Petersburg, Florida, United States, 33705
      • Recruiting
      • Florida Cancer Specialists
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • BRCR Global
    • West Palm Beach, Florida, United States, 33401
      • Recruiting
      • Florida Cancer Specialists
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Sarah Cannon Research Institute (SCRI)/ Hematology/ Oncology Clinic
  • Maine
    • Scarborough, Maine, United States, 04074
      • Recruiting
      • New England Cancer Specialists
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • American Oncology Partners
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • HealthPartners Cancer Research Center
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone-Laura and Isaac Perlmutter Cancer Center
    • New York, New York, United States, 12065
      • Recruiting
      • USOR - New York Oncology/ Hematology
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Recruiting
      • Sanford Roger Maris Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • OHC USOR (US Oncology Network Site)
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • Zangmeister Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Willamette Valley Cancer Institute and Research Center
    • Portland, Oregon, United States, 97227
      • Recruiting
      • Kaiser Permanente Northwest Center for Health Research
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Hollings Cancer Center, Charleston, SC
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center University of Texas
    • Webster, Texas, United States, 77598
      • Recruiting
      • Texas Oncology- Webster
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
  • Washington
    • Vancouver, Washington, United States, 98684
      • Recruiting
      • Compass Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 3rd generation EGFR-TKI treatment and have progressed on or following
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.
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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	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.; Other Names: Carboplatin; Pemetrexed
Experimental: 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.	Drug: 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.; Other Names: Carboplatin; Pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.	Up to 2 years
Overall Survival (OS)	Overall Survival (OS) in the ITT population	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 2 years
DCR	Disease control rate (DCR), which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1	Up to 2 years
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.	Up to 2 years
TTR	TTR is defined as the time to response base on RECIST v1.1	Up to 2 years
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.	Up to 2 years
AE	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.	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
Observed concentrations of AK112	The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration	through study completion, an average of 2 year
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)	From first dose of AK112 through 90 days after last dose of AK112,up to 2 years

Collaborators and Investigators

• Sponsor: Summit Therapeutics
• Collaborators: Akeso
• Investigators: Principal Investigator: Li Zhang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Carboplatin; Pemetrexed
• Other Study ID Numbers: AK112-301; HARMONi (Other Identifier: Summit Therapeutics)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No