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Non-Small Cell Lung CancerPhase 1/2NCT07535463

A Study of Ivonescimab, Chemotherapy, and Stereotactic Radiosurgery for People With Non-Small Cell Lung Cancer

A Phase 1/2 study testing Ivonescimab and Stereotactic Radiosurgery in people with Non-Small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The researchers are doing this study to test the safety of ivonescimab given in combination with standard chemotherapy and stereotactic radiosurgery (SRS) in people with non-small cell lung cancer (NSCLC) that has spread to the brain (brain metastases). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
Ivonescimab and Stereotactic Radiosurgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
7 sitesUnited States
Study dates
10 Apr 2026to Apr 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed non-small cell lung cancer, including squamous and non-squamous histologies.
  • At least one brain metastasis measuring ≥ 1.0 cm and ≤ 3.5 cm in diameter, deemed safe for treatment with SRS by an attending radiation oncologist
  • PD-L1 tumor proportion score available
  • ECOG performance status 0-1 (See Appendix II for performance status criteria)
  • Age ≥ 18 years
  • Expected life expectancy greater than 3 months
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  • Participant or Legally Authorized Representative (LAR) able to provide written informed consent
  • Participant willing to comply with all requirements of study participation
  • Adequate Organ Function:
  • Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening CBC): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L ii. Platelet count ≥ 100 × 10^9/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 ≥30 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
  • Liver:
  • Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN, 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 prothrombin 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.
  • Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, hypothyroidism requiring medication and alopecia can be resolved to Grade ≤2)
  • Steroid treatment (dexamethasone) is allowed and patients will be eligible if patients have been tapered to a dose equivalent of ≤ 4mg dexamethasone once a day for at least one week prior to enrollment. For example, a patient who received a 10mg bolus of dexamethasone in the emergency department after an MRI demonstrated brain metastases, as long as they have been tapered to a dose of 4mg or less for at least one week prior to enrollment
  • 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 90 days after the last dose of the ivonescimab, which overlaps with the period during which patients are treated with SRS.
  • Unsterilized male patients 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 90 days after the last dose of ivonescimab.
  • 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 90 days after the last dose of ivonescimab, which overlaps with the period during which patients are treated with SRS.
  • See Appendix III - Contraceptive Guidelines

Who cannot join

  • Histologically confirmed small cell lung cancer.
  • Previous brain-directed radiotherapy will be permitted; however, direct re-treatment with SRS of a brain metastasis that had previously received SRS is not permitted; sites will be reviewed by the P.I. (L.R.G.P.).
  • Unable to undergo contrast-enhanced brain MRI.
  • Brain metastasis in a brainstem location ≥ 1.0 cm in diameter.
  • Leptomeningeal disease.
  • Previous treatment with immunotherapy. Note: for subjects who have received adjuvant/neoadjuvant immunotherapy for non-metastatic diseases for the purpose of cure, if the disease progression is reported ≥ 12 months after the end of last immunotherapy, the subjects can be enrolled in this study.
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  • Subjects who have received previous treatment with standard-of-care targeted therapies against EGFR, ALK, and ROS1 can be enrolled in this study, at the discretion of the PI.
  • Previous history of malignant tumor other than NSCLC within 3 years before enrollment.
  • Note: for subjects with malignant tumors that have been cured by local treatment (e.g.,basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast cancer in situ) or are not on any active systemic anti-tumor therapy, the subjects can be enrolled in this study in discussion with the PI.
  • Major surgical procedures or serious trauma within 4 weeks of enrollment 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 of enrollment.
  • History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to
  • Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
  • Nasal bleeding /epistaxis (bloody nasal discharge is allowed)
  • Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (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 . Blood pressure will be measured using triple blood pressure assessment to determine the average.
  • Active autoimmune or lung disease requiring systemic therapy (e.g., with disease modifying drugs, dexamethasone >4 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment, however the following will be allowed:
  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
  • Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted
  • History of major diseases before enrollment, specifically:
  • Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2 - see Appendix IV - NYHA Classification) or unstable vascular disease (e.g., aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmias, myocardial ischemia)
  • 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 enrollment.
  • 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 enrollment.
  • Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment
  • 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 enrollment.
  • Imaging during the screening period shows that the patient has:
  • 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, 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.
  • 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.
  • Previous history of intracranial hemorrhage; if one of the visible brain metastases is deemed to have a component of intratumoral hemorrhage, then they will be evaluated by the principal investigator with Neuroradiology to determine if the patient may be enrolled in this study.
  • Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrollment, 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 enrollment, 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 enrollment (excluding antiviral therapy for hepatitis B or C).
  • Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 5.
  • Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic.
  • Note: Patients managed with indwelling catheters (e.g., PleurX) are allowed.
  • History of non-infectious pneumonia requiring systemic corticosteroids (>dexamethasone 4 mg equivalent daily), or current interstitial lung disease.
  • Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
  • Known history of human immunodeficiency virus (HIV) whose viral load is not controlled.
  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • 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 polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrollment.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • 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 anticancer 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 patient'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 patient to participate, in the opinion of the treating investigator.
  • Patient is breastfeeding or plans to breastfeed during the study.

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Luke Pike, MD, PhD contact

212-639-8157

pikel@mskcc.org

Mark Awad, M.D., PhD contact

646-608-2928

7 sites in 1 country

United States7 sites, 7 recruiting

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

    Basking Ridge, New Jersey, 07920

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

    Commack, New York, 11725

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Westchester (All Protocol Activities)

    Harrison, New York, 10604

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Monmouth (All Protocol Activities)

    Middletown, New Jersey, 07748

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Bergen (All Protocol Activities)

    Montvale, New Jersey, 07645

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

  • Memorial Sloan Kettering Nassau (All Protocol Activities)

    Rockville Centre, New York, 11553

    Luke Pike, MD, PhD, 212-639-8157

    Recruiting

Other trials in United States

About this study

Official title: Safety and Efficacy of Ivonescimab and Chemotherapy Plus Stereotactic Radiosurgery (SRS) in the Treatment of Non-Small Cell Lung Cancer Brain Metastases

The researchers are doing this study to test the safety of ivonescimab given in combination with standard chemotherapy and stereotactic radiosurgery (SRS) in people with non-small cell lung cancer (NSCLC) that has spread to the brain (brain metastases). The researchers will test different doses of the study drug to find the best dose that causes few or mild side effects in participants. Once the dose is found, the researchers will test it in a new group of participants to see if it is effective in treating their NSCLC brain metastases.

Being tested
Ivonescimab, Stereotactic Radiosurgery
Keywords
Ivonescimab, Stereotactic Radiosurgery, 26-021
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvonescimabDrug

    Ivonescimab will be administered IV on Day 1 of the first cycle starting at 10 mg/kg with chemotherapy. Dose escalation will proceed to 15 mg/kg and 20 mg/kg as tolerated.

  • Stereotactic RadiosurgeryRadiation

    (9Gy x 3 fractions) starting on Days 7-10.

Study groups in NCT07535463
Study groupRoleWhat they receive
Ivonescimab, Chemotherapy, and Stereotactic RadiosurgeryExperimentalIn the Phase I portion of the study, patients with NSCLC brain metastases will receive ivonescimab at a starting dose of 10 mg/kg on Day 1 (with chemotherapy), followed by stereotactic radiosurgery (9Gy x 3 fractions) starting on Days 7-10. Following a toxicity check at Day 21, patients will receive standard dosing of ivonescimab with chemotherapy at the discretion of the medical oncologist. In the Phase II portion of the study, patients will receive the RP2D from the initial phase of ivonescimab and chemotherapy on C1D1, followed by stereotactic radiosurgery (9Gy x 3 fractions) starting on Days 7-10.
Receives: Drug: Ivonescimab; Radiation: Stereotactic Radiosurgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. identify the Recommended Phase 2 Dose (RPD2)

    per NCI CTCAE version 5.0 criteria

    Measured: 21 days

  2. intracranial progression-free survival (iPFS),

    defined as the time of treatment start to radiologically confirmed intracranial progression or death from any cause.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2026
  2. Study start10 Apr 2026
  3. Primary completionApr 2028 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single arm, phase I/II trial.
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07535463
Sponsor's protocol ID
26-021
Status last verified
Apr 2026
First submitted
10 Apr 2026
Last updated
17 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ivonescimab and Stereotactic Radiosurgery in people with Non-Small Cell Lung Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Luke Pike, MD, PhD (212-639-8157, pikel@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

identify the Recommended Phase 2 Dose (RPD2) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07535463.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.

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