Phase 3 Clinical Study of AK112 for NSCLC Patients

Non-Squamous Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05184712
• Other study ID #: AK112-301
• Secondary ID: HARMONi
• Status: Recruiting
• Phase: Phase 3
• Start date: January 1, 2022
• Est. completion date: January 1, 2026

Study information

• Verified date: April 2024
• Source: Summit Therapeutics
• Contact: Lori Styles, MD
• Phone: 1-833-256-0522
• Email: medicalinformation[@]smmttx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 470
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Squamous Non-small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute, University of Alberta, Edmonton AB	Edmonton	Alberta
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Hospital Laval	Québec	Quebec
Canada	Allan Blair Cancer Center	Regina	Saskatchewan
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Canada	BC Cancer	Vancouver	British Columbia
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
France	Service de Pneumologie, CHI Créteil	Créteil
France	Hopital Bichat-Claude Bernard	Paris
France	Institut Curie	Paris
Italy	Campus Bio-Medico University	Roma
Spain	Badalona-Hospital Germans Trias i Pujol	Barcelona
Spain	Institutes Català d'Oncologia, Badalona-Hospital Germans Trias i Pujol	Barcelona
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Teresa Herrera	Coruña
Spain	Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria	Las Palmas
Spain	Lucus Augusti University Hospital	Lugo
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Instituto de Investigación Sanitaria-Fundación Jiménez Díaz	Madrid
Spain	Puerta de Hierro University Hospital, Majadahonda	Majadahonda
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Hospital Universitario Clínico San Carlos	San Carlos
Spain	Hospital Universitario Nuestra Señora de Valme	Sevilla
United States	Texas Oncology	Austin	Texas
United States	CBCC Global Research Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Sarah Cannon Research Institute (SCRI)/ Hematology/ Oncology Clinic	Baton Rouge	Louisiana
United States	American Oncology Partners	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Hollings Cancer Center, Charleston, SC	Charleston	South Carolina
United States	OHC USOR (US Oncology Network Site)	Cincinnati	Ohio
United States	Zangmeister Cancer Center	Columbus	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	MD Anderson Cancer Center University of Texas	Houston	Texas
United States	UC San Diego	La Jolla	California
United States	Rocky Mountain Cancer Centers, LLP	Lone Tree	Colorado
United States	Palo Alto Medical Foundation Research Institute	Los Altos	California
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	NYU Langone-Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	USOR - New York Oncology/ Hematology	New York	New York
United States	Florida Cancer Associates-Ocala Oncology	Ocala	Florida
United States	Hematology-Oncology Medical Group of Orange County, Inc	Orange	California
United States	UC Irvine	Orange	California
United States	BRCR Global	Plantation	Florida
United States	Kaiser Permanente Northwest Center for Health Research	Portland	Oregon
United States	Sutter Cancer Center	Sacramento	California
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	HealthPartners Cancer Research Center	Saint Paul	Minnesota
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	California Pacific Medical Center	San Francisco	California
United States	Providence Medical Foundation	Santa Rosa	California
United States	New England Cancer Specialists	Scarborough	Maine
United States	BRCR Global	Tamarac	Florida
United States	Compass Oncology	Vancouver	Washington
United States	Texas Oncology- Webster	Webster	Texas
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	Presbyterian Intercommunity Hospital (PIH)	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Summit Therapeutics	Akeso

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.	Up to 2 years
Primary	Overall Survival (OS)	Overall Survival (OS) in the ITT population	Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	TTR	TTR is defined as the time to response base on RECIST v1.1	Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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