Authorised Therapeutic confirmatory (Phase III) Metastatic Non-small Cell Lung Cancer

HARMONi-3

EU CTIS ID: 2024-513087-26-00

What this study is testing

To compare overall survival (OS) between ivonescimab combined with platinum-doublet chemotherapy and pembrolizumab combined with platinum-doublet chemotherapy. To compare independent radiology review committee (IRRC) assessed progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between ivonescimab combined with platinum-doublet chemotherapy and pembrolizumab combined with platinum-doublet chemotherapy.

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

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 • 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 x ULN, and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti- coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.
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 ivonescimab/pembrolizumab or until 6 months after last dose of chemotherapy (whichever is longer).
Male patient having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) for the duration of the treatment period until 120 days after the last dose of ivonescimab/pembrolizumab and/or until 6 months after last dose of chemotherapy (whichever is longer). Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 120 days after the last dose of ivonescimab/pembrolizumab or until 6 months after last dose of chemotherapy (whichever is longer).
Age ≥ 18 years old at the time of enrollment

You likely can't join if

Histologic or cytopathologic evidence of the presence of small cell lung carcinoma.
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 7 days 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 (as determined by the investigator) 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.

See the full eligibility criteria

Who can join

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 • 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 x ULN, and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti- coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.
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 ivonescimab/pembrolizumab or until 6 months after last dose of chemotherapy (whichever is longer).
Male patient having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) for the duration of the treatment period until 120 days after the last dose of ivonescimab/pembrolizumab and/or until 6 months after last dose of chemotherapy (whichever is longer). Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 120 days after the last dose of ivonescimab/pembrolizumab or until 6 months after last dose of chemotherapy (whichever is longer).
Age ≥ 18 years old at the time of enrollment
Eastern Cooperative Oncology Group (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 or non-squamous NSCLC.
Patients must have a TPS or TC for PD-L1 expression prior to randomization. The TPS/TC score can be obtained from an existing report or be performed any time before study entry using archival tissue utilizing on a clinical assay approved/cleared by local health authorities. If site is unable to perform a TPS/TC score locally, then the site should provide tumor tissue (fresh or achival) for central TPS/TC determination.
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.
No prior systemic treatment for metastatic NSCLC. Patients receiving adjuvant or neoadjuvant therapy or curative-intent chemoradiotherapy with or without PD- 1/L1 inhibitors are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.

What rules you out

Histologic or cytopathologic evidence of the presence of small cell lung carcinoma.
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 7 days 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 (as determined by the investigator) 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. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. b. Nasal bleeding /epistaxis (bloody nasal discharge is allowed). c. Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed. The use of full-dose anticoagulants is permitted as long as the INR or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution.
Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic. Note: Patients managed with indwelling catheters (eg, PleurX) are allowed.
History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease
Active or prior history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea)
Known actionable genomic alterations (epidermal growth factor receptors [EGFR], anaplastic lymphoma kinase [ALK], ROS1, and BRAF V600E) for which first-line approved therapies are available. For non-squamous histology patients, actionable driver mutation testing results are required before randomization.
Known history of human immunodeficiency virus (HIV) whose viral load is not controlled
Current use of systemic corticosteroids (≥10 mg daily prednisone or equivalent)
Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by PCR on appropriate anti-viral therapy with acceptable tolerability for one month prior to randomization. All active hepatitis C patients (hepatitis C virus [HCV] antibody positive with HCV RNA levels above the lower limit of detection) are excluded.
Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies
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
Patient is breastfeeding or plans to breastfeed during the study
Other conditions where the investigator considers the patient inappropriate for enrollment
Has received any prior therapy for NSCLC in the metastatic setting. Note: Local radiation therapy (plus/minus corticosteroids) for CNS or bone metastases is allowed.
Concurrent enrollment in another clinical study, unless patient is enrolled in a non-interventional clinical study or is completing survival follow-up.
Imaging during the screening period shows that the patient has: a. Radiologically documented evidence of major blood vessel invasion (central pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery, common carotid artery, subclavian artery, superior vena cava) or tumor invading organs (heart, pericardium, trachea, esophagus, central bronchi [not including segmental bronchi]) or if there is a risk of esophagotracheal or esophagopleural fistula in the opinion of the investigator. b. Radiographic evidence of major blood vessel encasement with narrowing of the vessel or intratumor lung cavitation or necrosis that the investigator determines will pose a significantly increased risk of bleeding.
Symptomatic CNS metastases, CNS metastasis with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease Note: Patients must have stopped corticosteroids or be on stable corticosteroid therapy (prednisone ≤ 10 mg daily or equivalent).
Other prior malignancy unless the patient has undergone curative therapy with no evidence of disease recurrence within 3 years prior to randomization. The following malignancies will be allowed without the 3-year interval after adequate treatment: basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, other in situ cancers, or other local tumors (e.g. prostate cancer) that are considered cured.
Active autoimmune or lung disease requiring systemic therapy (eg, with disease- modifying 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. Use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted.
History of major diseases before randomization, specifically: a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) 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 any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event 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 12 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.

The study team makes the final eligibility decision.

Where it's taking place

Mexico
China
Japan
Turkey
Serbia
United States
United Kingdom
Canada

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Mexico; China; Japan; Turkey; Serbia; United States and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.