Trial Title:
Phase III Study of AK112 for NSCLC Patients
NCT ID:
NCT06396065
Condition:
Non-Squamous Non-small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Carboplatin
Pemetrexed
Conditions: Keywords:
NSCLC
EGFR Positive
ivonescimab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
AK112 Injection
Description:
Subjects will receive 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.
Arm group label:
AK112 in combination with Pemetrexed and Carboplatin
Other name:
Pemetrexed
Other name:
Carboplatin
Intervention type:
Drug
Intervention name:
Placebo Injection
Description:
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.
Arm group label:
Placebo in combination with Pemetrexed and Carboplatin
Other name:
Pemetrexed
Other name:
Carboplatin
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 Progressed on or Following
Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (HARMONi)
Detailed description:
The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare
Ivonescimab (SMT112 /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 420 subjects will be randomized to two
treatment arms at the ratio of 1:1. Each enrolled subject will receive an intravenous
infusion of the Ivonescimab (SMT112 /AK112)/Placebo Plus Pemetrexed and Carboplatin
(Q3W,up to 4 cycles) in treatment periods per the randomization schedule. Afterward,
Ivonescimab (SMT112 /AK112)/ Placebo Plus Pemetrexed will be used for maintenance
treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
Criteria for 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.
(For patients from North America and Europe, there will be no upper age cutoff)
3. ECOG performance status score of 0 or 1.
4. Expected survival ≥3 months.
5. Histologically or cytology-confirmed, locally advanced (Stage IIIB/IIIC) or
metastatic (Stage IV) non-squamous NSCLC (according to TNM staging of lung cancer,
8th edition) that cannot be completely resected by surgery and cannot receive
radical concurrent/sequential chemoradiation.
6. EGFR activation mutations that are confirmed by tumor histology or cytology or blood
test before enrollment (eg, exon 18 point mutations, exon 19 deletions, exon 20
point mutations, and exon 21 point mutations). Patients must provide a previous EGFR
mutation test report, otherwise tumor tissue samples, peripheral blood samples, or
pleural fluid samples will need to be collected for EGFR status testing prior to
enrollment.
7. Prior treatment with EGFR TKI and treatment failure, meeting any of the following
requirements: Progression after treatment with first- or second-generation EGFR TKI,
and confirmation of absence of T790M mutation after progression (only for patients
enrolled in China). Progression after treatment with a third-generation EGFR TKI
(eg, osimertinib, ametinib, vometinib). Note, for North America and Europe patients
only.
8. According to RECIST v1.1, there is at least 1 measurable noncerebral lesion.
9. Adequate organ function determined by the following requirements
10. Female patients of childbearing age have a negative serum pregnancy test result
within 3 days before the first dose
11. If a female patient of childbearing potential has sex with an unsterilized male
partner, the patient must use a highly effective method of contraception from the
beginning of screening and must agree to continue using these precautions until 120
days after the last dose of the study drug or until 6 months after the last
carboplatin and pemetrexed dose (whichever is longer).
12. If an unsterilized male patient has sex with a female partner of childbearing
potential, the patient must use an effective method of contraception from the
beginning of screening to day 120 after the last dose or until 6 months after the
last carboplatin and pemetrexed dose (whichever is longer). The decision to stop
contraception after this time point should be discussed with investigator.
Exclusion Criteria:
1. Histologic or cytopathologic evidence of the presence of a small cell carcinoma
component, or a predominantly squamous cell carcinoma.
2. Patients who have received immune checkpoint inhibitors (eg, anti-PD-1/L1
antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.)
3. Received prior systemic chemotherapy, anti-angiogenic therapy, or more than one
prior line of antitumor therapy (other than EGFR inhibitors) for advanced stage
(IIIB to IV) NSCLC.
4. Concurrent enrollment in another clinical study, unless it is a noninterventional
clinical study or the follow-up period of the interventional study is more than 4
weeks from the last dose of the prior clinical study or more than 5 half-lives of
the prior study drug, whichever is shorter.
5. Received EGFR inhibitor therapy within 2 weeks (with the exception of osimertinib to
be within 7 days) prior to the first dose; received nonspecific immunomodulatory
therapy (eg, interleukin, interferon, thymus peptide, tumor necrosis factor) within
2 weeks prior to the first dose, excluding IL-11 for the treatment of
thrombocytopenia; have received Chinese herbal medicines or proprietary Chinese
medicines with antitumor indications within 1 week before the first dose.
6. Imaging during the screening period shows that the tumor surrounds important blood
vessels or has obvious necrosis and/or cavitation of tumor lesions within the lung
parenchyma.
7. Imaging during the screening period shows that the tumor invades the surrounding
vital organs and blood vessels, such as the heart and pericardium, trachea,
esophagus, aorta, superior vena cava, or patient is at risk of esophageal tracheal
fistula or esophageal pleural fistula.
8. Symptomatic metastases of the central nervous system.
9. Malignant tumors other than NSCLC within 3 years before the first dose.
10. Active autoimmune disease requiring systemic therapy (eg, with disease-modifying
drugs, corticosteroids, immunosuppressant therapy) within 2 years prior to the first
dose (excluding ir AEs due to PD-1/L1 inhibitors). Replacement therapy (eg,
thyroxine, insulin, or physiologic corticosteroid replacement therapy (prednisone ≤
10 mg daily or equivalent) for adrenal or pituitary insufficiency) is permitted.
11. There is a history of major diseases before the first dose
12. History of perforation of the gastrointestinal tract and/or fistula, history of
gastrointestinal obstruction (including incomplete intestinal obstruction requiring
parenteral nutrition), extensive bowel resection (partial colectomy or extensive
small bowel resection, complicated by chronic diarrhea) within 6 months before the
first study drug administration.
13. Patients with >30 Gy of chest radiation therapy within 6 months prior to the first
dose, nonthoracic radiation therapy >30 Gy within 4 weeks prior to the first dose,
and palliative radiation therapy of ≤30 Gy within 2 weeks prior to the first dose
and failed to recover from the toxicity and/or complications of these interventions
to NCI CTCAE Grade ≤1 (except hair loss and fatigue). Palliative radiotherapy for
symptom control is permitted if it has been completed at least 2 weeks before the
first dose, and no additional radiotherapy for the same lesion is planned.
14. Inactivated vaccines are allowed. Patients are excluded if they have received a live
vaccine or live attenuated vaccine within 4 weeks prior to the first dose, or if
they are scheduled to receive a live vaccine or live attenuated vaccine during the
study period.
15. Severe infection within 4 weeks prior to the first dose, including but not limited
to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active
infection that has received systemic anti-infective therapy within 2 weeks prior to
the first dose (excluding antiviral therapy for hepatitis B or C)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CBCC Global Research
Address:
City:
Bakersfield
Zip:
93309
Country:
United States
Facility:
Name:
UC San Diego
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Facility:
Name:
Valkyrie Clinical Trials
Address:
City:
Los Angeles
Zip:
90067
Country:
United States
Facility:
Name:
UCLA Department of Medicine - Hematology/Oncology
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Facility:
Name:
Palo Alto Medical Foundation Research Institute
Address:
City:
Mountain View
Zip:
94040
Country:
United States
Facility:
Name:
Providence St. Joseph
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
UC Irvine
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
Sutter Cancer center
Address:
City:
Sacramento
Zip:
95816
Country:
United States
Facility:
Name:
UC DAVIS Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Facility:
Name:
Sharp Memorial Hospital
Address:
City:
San Diego
Zip:
92123
Country:
United States
Facility:
Name:
California Pacific Medical Center
Address:
City:
San Francisco
Zip:
94115
Country:
United States
Facility:
Name:
Providence Medical Foundation
Address:
City:
Santa Rosa
Zip:
95403
Country:
United States
Facility:
Name:
Presbyterian Intercommunity Hospital
Address:
City:
Whittier
Zip:
90602
Country:
United States
Facility:
Name:
Rocky Mountain Cancer Center
Address:
City:
Lone Tree
Zip:
80124
Country:
United States
Facility:
Name:
The Oncology Institute of Hope & Innovation
Address:
City:
Fort Lauderdale
Zip:
33308
Country:
United States
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Facility:
Name:
Florida Cancer Associates - Ocala Oncology
Address:
City:
Ocala
Zip:
34474
Country:
United States
Facility:
Name:
BRCR Global
Address:
City:
Plantation
Zip:
33322
Country:
United States
Facility:
Name:
Florida Cancer Specialists - North
Address:
City:
Saint Petersburg
Zip:
33705
Country:
United States
Facility:
Name:
BRCR Global
Address:
City:
Tamarac
Zip:
33321
Country:
United States
Facility:
Name:
Florida Cancer Specialists -East
Address:
City:
West Palm Beach
Zip:
33401
Country:
United States
Facility:
Name:
Hematology/Oncology Clinic - SCRI
Address:
City:
Baton Rouge
Zip:
70809
Country:
United States
Facility:
Name:
New England Cancer Specialists
Address:
City:
Scarborough
Zip:
04074
Country:
United States
Facility:
Name:
American Oncology Partners
Address:
City:
Bethesda
Zip:
20817
Country:
United States
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
HealthPartners Cancer Research Center
Address:
City:
Saint Paul
Zip:
55101
Country:
United States
Facility:
Name:
New York Oncology/Hematology
Address:
City:
Clifton Park
Zip:
12065
Country:
United States
Facility:
Name:
NYU Langone Laura and Isaac Perlmutter Cancer Center
Address:
City:
New York
Zip:
10016
Country:
United States
Facility:
Name:
Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Facility:
Name:
Sanford Roger Maris Cancer Center
Address:
City:
Fargo
Zip:
58102
Country:
United States
Facility:
Name:
Zangmeister Cancer Center
Address:
City:
Columbus
Zip:
43219
Country:
United States
Facility:
Name:
Oncology Hematology Care
Address:
City:
Fairfield
Zip:
45014
Country:
United States
Facility:
Name:
Williamette Valley Cancer Institute and Research
Address:
City:
Eugene
Zip:
97401
Country:
United States
Facility:
Name:
Kaiser Permanente Northwest
Address:
City:
Portland
Zip:
97227
Country:
United States
Facility:
Name:
Medical University South Carolina
Address:
City:
Charleston
Zip:
29425
Country:
United States
Facility:
Name:
Baptist Hospital
Address:
City:
Memphis
Zip:
38120
Country:
United States
Facility:
Name:
Texas Oncology South Austin
Address:
City:
Austin
Zip:
78745
Country:
United States
Facility:
Name:
Texas Oncology Baylor Charles A. Sammons Cancer Center
Address:
City:
Dallas
Zip:
75246
Country:
United States
Facility:
Name:
MD Anderson University of Texas
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Texas Oncology Webster
Address:
City:
Webster
Zip:
77598
Country:
United States
Facility:
Name:
Virginia Cancer specialisits
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Facility:
Name:
Compass Oncology
Address:
City:
Vancouver
Zip:
98684
Country:
United States
Facility:
Name:
Cross cancer Institute
Address:
City:
Edmonton
Zip:
T6g 1Z2
Country:
Canada
Facility:
Name:
BC Cancer
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Facility:
Name:
Lung Cancer Canada
Address:
City:
Ottawa
Zip:
K1H 8L6
Country:
Canada
Facility:
Name:
Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5g 2M9
Country:
Canada
Facility:
Name:
Allan Blaire Cancer Centre
Address:
City:
Regina
Zip:
S4T 7T1
Country:
Canada
Facility:
Name:
Universite Hospital Laval
Address:
City:
Québec
Zip:
G1V 4G5
Country:
Canada
Facility:
Name:
CHI Creteil
Address:
City:
Creteil
Zip:
94010
Country:
France
Facility:
Name:
Léon Bérard Cancer Center, Lyon
Address:
City:
Lyon
Zip:
69008
Country:
France
Facility:
Name:
Hospital Bichat-Claude Bernard
Address:
City:
Paris
Zip:
75018
Country:
France
Facility:
Name:
Institut Curie
Address:
City:
Paris
Zip:
75248
Country:
France
Facility:
Name:
Gustave Roussy Cancer
Address:
City:
Villejuif
Zip:
94800
Country:
France
Facility:
Name:
Istituto Nazionale dei Tumori
Address:
City:
Milan
Zip:
20133
Country:
Italy
Facility:
Name:
Instituto Europeo di Oncologia
Address:
City:
Milan
Zip:
20141
Country:
Italy
Facility:
Name:
University Hospital of Parma
Address:
City:
Parma
Zip:
43126
Country:
Italy
Facility:
Name:
Campus Bio-Medico University
Address:
City:
Roma
Zip:
00128
Country:
Italy
Facility:
Name:
Istituto Nazionale Tumori, Regina Elena
Address:
City:
Rome
Zip:
00144
Country:
Italy
Facility:
Name:
Vall d'Hebron Institute of Oncology
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Facility:
Name:
Badalona-Hospital Germans Trias i Pujol
Address:
City:
Barcelona
Zip:
08916
Country:
Spain
Facility:
Name:
Hospital Teresa Herrera
Address:
City:
Coruña
Zip:
15006
Country:
Spain
Facility:
Name:
omplejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria
Address:
City:
Las Palmas
Zip:
35016
Country:
Spain
Facility:
Name:
Lucus Augusti University Hospital
Address:
City:
Lugo
Zip:
27002
Country:
Spain
Facility:
Name:
Hospital General Universitario Gregorio Maranon
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Facility:
Name:
Hospital Universitario Ramon y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Facility:
Name:
Hospital Universitario Clinico San Carlos
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Facility:
Name:
Puerta de Hierro University Hospital
Address:
City:
Majadahonda
Zip:
28222
Country:
Spain
Facility:
Name:
Hospital Regional Universitario de Malaga
Address:
City:
Malaga
Zip:
29011
Country:
Spain
Facility:
Name:
Hospital Universitario Nuestro Senora de Valme
Address:
City:
Sevilla
Zip:
41014
Country:
Spain
Facility:
Name:
The Royal Marsden
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4GJ
Country:
United Kingdom
Start date:
May 4, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Summit Therapeutics
Agency class:
Industry
Collaborator:
Agency:
Akeso
Agency class:
Industry
Source:
Summit Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06396065
