A Randomized, Controlled, Multiregional Phase 3 Study of Ivonescimab Combined with Chemotherapy Versus Pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer

Summit Therapeutics Sub Inc.47 sites in 7 countries135 target enrollmentJanuary 5, 2024

Interventionsivonescimab

Overview

Phase: Phase 3
Intervention: ivonescimab
Conditions: Not specified
Sponsor: Summit Therapeutics Sub Inc.
Enrollment: 135
Locations: 47
Primary Endpoint: Overall Survival (OS)
Status: Withdrawn
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

To compare overall survival (OS) between ivonescimab combined with carboplatin and paclitaxel or nab-paclitaxel versus pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel

Registry

euclinicaltrials.eu

Start Date

January 5, 2024

End Date

TBD

Last Updated

2 years ago

Investigators

Sponsor

Summit Therapeutics Sub Inc.

Responsible Party

Principal Investigator

Medical Information

Scientific

Summit Therapeutics Sub Inc.

Eligibility Criteria

Inclusion Criteria

•Voluntarily sign a written informed consent form (ICF)
•Adequate Organ Function: a. Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening CBC): i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L ii. Platelet count ≥ 100 × 109/L iii. Hemoglobin ≥ 9.0 g/dL b. Kidneys: i. Creatinine clearance* (CrCL) ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by BSA is not required for eGFR) CrCL or eGFR can be determined using the calculator from the National Kidney Foundation website (www.kidney.org). ii. Urine protein < 2+ or 24-hour urine protein quantification < 1.0 g c. Liver: i. Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastases, AST and ALT ≤ 5 × ULN d. Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy or prophylactic coagulation)
•Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
•Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the study treatment.
•Unsterilized male patient having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until Day 120 after the last dose of study treatment and until 6 months after last carboplatin dose (whichever is longer).
•Age ≥ 18 years old at the time of enrollment
•ECOG performance status score of 0 or 1
•Expected life expectancy ≥ 3 months
•Metastatic (Stage IV) NSCLC, according to American Joint Committee on Cancer (AJCC) 8th edition
•Histologically or cytologically confirmed squamous NSCLC. Patients with mixed histology (eg, adenosquamous) are allowed if there is squamous component

Exclusion Criteria

•Histologic or cytopathologic evidence of the presence of small cell lung carcinoma, or non-squamous NSCLC histology.
•Patients with > 30 Gy of chest radiation therapy within 6 months prior to randomization; non-thoracic radiation therapy > 30 Gy within 4 weeks prior to randomization, or palliative radiation therapy of ≤ 30 Gy within 2 weeks prior to randomization
•Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 5
•Live vaccine or live attenuated vaccine within 4 weeks prior to planned randomization, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted
•Severe infection within 4 weeks prior to randomization, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to randomization (excluding antiviral therapy for hepatitis B or C)
•Major surgical procedures or serious trauma within 4 weeks prior to randomization, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to randomization.
•History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to randomization, including but not limited to: a. Gastrointestinal bleeding b. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. c. Nasal bleeding /epistaxis (bloody nasal discharge is allowed) d. Need for therapeutic anticoagulant therapy within 14 days prior to randomization Note: Prophylactic anticoagulation for DVT/PE or to maintain venous patency is allowed.
•Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
•Presence of pleural effusions, pericardial effusions, or ascites that is clinically symptomatic or requires repeated drainage
•History of noninfectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease

Arms & Interventions

ivonescimab

Participants receiving ivonescimab

Intervention: ivonescimab

Outcomes

Primary Outcomes

Overall Survival (OS)

Secondary Outcomes

PFS assessed by investigator based on RECIST v1.1
ORR (including DoR) assessed by investigator based on RECIST v1.1
Safety assessment: incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results
PK characteristics: ivonescimab serum drug concentrations profiles
Immunogenicity: number and percentage of patients with detectable anti-ivonescimab antibody (ADA) at baseline and post treatment