IVONESCIMAB for Metastatic squamous non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Voluntarily sign a written informed consent form (ICF)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Age ≥ 18 years old at the time of enrollment"}
• {"criterion_text":"- ECOG performance status score of 0 or 1"}
• {"criterion_text":"- Expected life expectancy ≥ 3 months"}
• {"criterion_text":"- Metastatic (Stage IV) NSCLC, according to American Joint Committee on Cancer (AJCC) 8th edition"}
• {"criterion_text":"- Histologically or cytologically confirmed squamous NSCLC. Patients with mixed histology (eg, adenosquamous) are allowed if there is squamous component"}
• {"criterion_text":"- Patients must have Tumor Proportion Score (TPS) with PD-L1 expression percent (from available reports or archival tumor tissue based on a clinical assay) or provide tissue for measurement of PD-L1 expression"}
• {"criterion_text":"- At least one measurable noncerebral lesion according to RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since radiotherapy. Sites of biopsy cannot be included as target lesions unless no other measurable lesions are present"}
• {"criterion_text":"- No prior systemic treatment for metastatic NSCLC. Patients receiving adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease. Note: Patients previously treated with PD-1/L1 inhibitors in the adjuvant / neoadjuvant setting are excluded."}

Exclusion criteria

• {"criterion_text":"- Histologic or cytopathologic evidence of the presence of small cell lung carcinoma, or non-squamous NSCLC histology."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 5"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy"}
• {"criterion_text":"- Presence of pleural effusions, pericardial effusions, or ascites that is clinically symptomatic or requires repeated drainage"}
• {"criterion_text":"- History of noninfectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease"}
• {"criterion_text":"- Active or prior history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea)"}
• {"criterion_text":"- Known actionable genomic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS1 or genes for which first-line approved therapies are available"}
• {"criterion_text":"- Known history of human immunodeficiency virus (HIV)"}
• {"criterion_text":"- Current use of systemic corticosteroids (≥10 mg daily prednisone or equivalent)"}
• {"criterion_text":"- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation"}
• {"criterion_text":"- Patients with untreated active hepatitis B are required to receive anti-hepatitis B virus (HBV) therapy for the duration of study treatment; all active hepatitis C patients (hepatitis C virus [HCV] antibody positive and HCV RNA levels above the lower limit of detection) are excluded."}
• {"criterion_text":"- Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies"}
• {"criterion_text":"- History or current evidence of any condition (medical [including adverse events from prior anti-cancer therapy, disorders secondary to tumor], surgical or psychiatric [including substance abuse]), or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the subject to participate, in the opinion of the treating investigator"}
• {"criterion_text":"- Patient is breastfeeding or plans to breastfeed during the study"}
• {"criterion_text":"- Other conditions where the investigator considers the patient inappropriate for enrollment"}
• {"criterion_text":"- Has received any prior therapy for NSCLC in the metastatic setting Note: Local therapy (plus/minus corticosteroids) for CNS or bone metastases is allowed."}
• {"criterion_text":"- Concurrent enrollment in another clinical study, unless patient is enrolled in a noninterventional clinical study"}
• {"criterion_text":"- Imaging during the screening period shows that the patient has: a. Radiologically documented evidence of major blood vessel invasion or encasement by cancer b. Radiographic evidence of intratumor cavitation"}
• {"criterion_text":"- Symptomatic CNS metastases, CNS metastasis ≥1.5 cm, CNS radiation within 2 weeks prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease Note: Patients with asymptomatic and untreated metastasis are eligible if the lesion is ≤ 0.5 cm and does not have hemorrhagic features. Patients with asymptomatic treated brain metastasis are eligible if the lesion is < 1.5 cm. Patients must have stopped corticosteroids for more than 3 days before randomization."}
• {"criterion_text":"- Other prior malignancy, with the following exceptions: a. If the patient has undergone curative therapy with no evidence of recurrence of the disease for 3 years prior to randomization, the following malignancies will be allowed: basal cell or squamous cell carcinoma of skin; superficial bladder cancer; and in situ cervical cancer, other in situ cancers, or other local tumors that are considered cured (eg, prostate cancer). b. If the patient was treated with systemic chemotherapy and has no evidence of recurrence of the prior malignancy for at least 5 years prior to randomization, the patient will be allowed to enroll into the study."}
• {"criterion_text":"- Active autoimmune or lung disease requiring systemic therapy (eg, with diseasemodifying drugs, prednisone ≥10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to randomization, however the following will be allowed: a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. b. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted."}
• {"criterion_text":"- History of major diseases before randomization, specifically: a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia) b. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before randomization c. History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to randomization d. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before randomization e. 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) within 6 months prior to randomization"}

Primary endpoints

• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- PFS assessed by investigator based on RECIST v1.1","definition_or_measurement_approach":"Progression-free survival assessed by investigator per RECIST v1.1"}
• {"endpoint_text":"- ORR (including DoR) assessed by investigator based on RECIST v1.1","definition_or_measurement_approach":"Objective response rate and duration of response assessed by investigator per RECIST v1.1"}
• {"endpoint_text":"- Safety assessment: incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results","definition_or_measurement_approach":"Incidence and severity of adverse events and clinically significant abnormal labs (as reported during study)"}
• {"endpoint_text":"- PK characteristics: ivonescimab serum drug concentrations profiles","definition_or_measurement_approach":"Serum concentration profiles of ivonescimab (pharmacokinetic sampling)"}
• {"endpoint_text":"- Immunogenicity: number and percentage of patients with detectable anti-ivonescimab antibody (ADA) at baseline and post treatment","definition_or_measurement_approach":"Number and percentage of patients with detectable anti-ivonescimab antibodies at baseline and post-treatment"}

France

Earliest CTIS Part Ii Submission Date

10-11-2023

Latest Decision Or Authorization Date

05-01-2024

Processing Time Days

56

Number Of Sites

5

Number Of Participants

16

Germany

Earliest CTIS Part Ii Submission Date

06-11-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

63

Number Of Sites

5

Number Of Participants

15

Ireland

Earliest CTIS Part Ii Submission Date

03-11-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

66

Number Of Sites

2

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

24-10-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

76

Number Of Sites

12

Number Of Participants

35

Spain

Earliest CTIS Part Ii Submission Date

20-11-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

49

Number Of Sites

16

Number Of Participants

44

Poland

Earliest CTIS Part Ii Submission Date

17-11-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

52

Number Of Sites

3

Number Of Participants

8

Greece

Earliest CTIS Part Ii Submission Date

07-09-2023

Latest Decision Or Authorization Date

08-01-2024

Processing Time Days

123

Number Of Sites

4

Number Of Participants

12

Primary sponsor

Full Name

Summit Therapeutics Sub Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.

Responsibilities

sponsorDuties codes: 1,12; contact info: info@nextcro.eu, +302106147282

Third parties

• {"country":"Greece","full_name":"Next CRO SYMVOULOI FARMAKEUTIKON EPICHEIRISEON M.E.P.E.","duties_or_roles":"sponsorDuties codes: 1,12","organisation_type":"Pharmaceutical company"}