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Non-Small Cell Lung CancerPhase 1/2NCT07535437

A Study of Ivonescimab in Combination With Dato-DXd or Osimertinib in People With Non-Small Cell Lung Cancer

A Phase 1/2 study testing Ivonescimab, Dato-DXd and Osimertinib 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
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Trial summary

The researchers are doing this study to find out whether ivonescimab in combination with datopotamab deruxtecan- (Dato-DXd) or osimertinib are safe and effective treatments in people with non-small cell lung cancer (NSCLC) that has an EGFR mutation. 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, Dato-DXd and Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
7 sitesUnited States
Study dates
9 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

  • Written informed consent by participant
  • Biopsy-proven metastatic non-small cell lung cancer
  • Somatic activating mutation in EGFR in pre-treatment tumor biopsy or cfDNA (including all mutations with sensitivity to osimertinib) by any CLIA certified assay.
  • Prior treatment with 3rd-generation EGFR TKI therapy and platinum-based chemotherapy (or ineligible for platinum-based chemotherapy)
  • At least one measurable (RECIST 1.1) indicator lesion not previously irradiated
  • ECOG PS 0-1
Show all 19Show fewer
  • Age ≥18 years old
  • Ability to swallow oral medications (Study Cohort B only)
  • Adequate organ function
  • AST, ALT ≤ 2.5 x ULN; For patients with liver metastases, AST and ALT ≤ 5 × ULN
  • Total bilirubin ≤ 1.5x ULN; For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN 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
  • Urine protein < 2+ or 24 hour urine protein quantification < 1.0 g
  • Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3
  • Hemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 2 weeks prior to screening assessment)
  • Platelets ≥100,000/mm3 (platelet transfusion is not allowed within 10 days prior to screening assessment)
  • 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). 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 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 90 days after the last dose of the ivonescimab and/or 3 months after last dose of Dato-DXd or 6 weeks after last dose of osimertinib
  • 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 plus spermicide) for the duration of the treatment period until 90 days after the last dose of ivonescimab and/or 6 months after the last dose of Dato-DXd or 6 weeks after last dose osimertinib. 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 and/or 3 months after the last dose of Dato-DXd or 6 weeks after last does of osimertinib.

Who cannot join

  • EGFR exon 20 insertion positive lung cancer with expected lack of sensitivity to osimertinib (Study Cohort B only).
  • Pregnant or lactating women
  • Participation in another clinical study and receiving treatment with an investigation product during the last 4 weeks before enrollment
  • Prior exposure to anti-PD-1 inhibitor therapy
  • Prior exposure to antibody drug conjugate (ADC) containing chemotherapeutic agent targeting topoisomerase I, TROP2 antibody (Study Cohort A only).
  • History of clinically significant corneal disease (Study Cohort A only)
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  • Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
  • Major surgical procedures or serious trauma within 4 weeks of study 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 prior study enrollment.
  • History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks of study 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.
  • Significant 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 first study drug treatment 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.
  • Active (eg, with disease modifying drugs, prednisone >10 mg daily or equivalent, immunosuppressant therapy) or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Short course of steroids if given for infection
  • Replacement therapy (eg, 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
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • History of major diseases before first study drug treatment, specifically:
  • 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 first study drug treatment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, 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 of study enrollment
  • History of any grade arterial 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 before first ivonescimab infusion
  • Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before first ivonescimab infusion
  • 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 before first ivonescimab infusion
  • 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.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of study drugs and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without- evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS radiation within 7 days prior to first study drug treatment, potential need for CNS radiation within the first cycle, or symptomatic leptomeningeal disease.
  • Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent).
  • Live vaccine or live attenuated vaccine within 4 weeks prior to first ivonescimab infusion, 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 first ivonescimab infusion, 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 first study drug treatment (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 (eg, PleurX) are allowed.
  • History of interstitial lung disease (ILD) requiring steroids
  • Current use of systemic corticosteroids (>10 mg daily prednisone or equivalent)
  • Known history of human immunodeficiency virus (HIV) whose viral load is not controlled.
  • 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 first study drug treatment. All patients with active hepatitis C (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 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.

Trial locations and contacts

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

Helena Yu, MD contact

646-608-3912

yuh@mskcc.org

Gregory Riely, MD, PhD contact

646-608-3913

7 sites in 1 country

United States7 sites, 7 recruiting

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

    Basking Ridge, New Jersey, 07920

    Helena Yu, MD, 646-608-3912

    Recruiting

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

    Commack, New York, 11725

    Helena Yu, MD, 646-608-3912

    Recruiting

  • Memorial Sloan Kettering Westchester (All Protocol Activities)

    Harrison, New York, 10604

    Helena Yu, MD, 646-608-3912

    Recruiting

  • Memorial Sloan Kettering Monmouth (All Protocol Activities)

    Middletown, New Jersey, 07748

    Helena Yu, MD, 646-608-3912

    Recruiting

  • Memorial Sloan Kettering Bergen (All Protocol Activities)

    Montvale, New Jersey, 07645

    Helena Yu, MD, 646-608-3912

    Recruiting

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

    Helena Yu, MD, 646-608-3912

    Gregory Riely, MD, PhD, 646-608-3913

    Recruiting

  • Memorial Sloan Kettering Nassau (All Protocol Activities)

    Uniondale, New York, 11553

    Helena Yu, MD, 646-608-3912

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1/2 Trial of Ivonescimab With Dato-DXd or Osimertinib in Patients With Metastatic EGFR-mutant Non-small Cell Lung Cancer That Progressed on EGFR TKI Therapy

The researchers are doing this study to find out whether ivonescimab in combination with datopotamab deruxtecan- (Dato-DXd) or osimertinib are safe and effective treatments in people with non-small cell lung cancer (NSCLC) that has an EGFR mutation. The researchers will test different doses of the Dato-DXd or osimertinib with an unchanging (fixed) dose of ivonescimab to find the best dose that causes few or mild side effects in participants. Once the dose is found the researchers will test ivonescimab with Dato-DXd or osimertinib in a new group of participants to see if it is effective in treating their NSCLC with an EGFR mutation.

Being tested
Ivonescimab, Dato-DXd, Osimertinib
Keywords
Ivonescimab, Dato-DXd, Osimertinib, Metastatic EGFR-Mutant, 25-366
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

    20 mg/kg

  • Dato-DXdDrug

    dose escalation

    4 mg/kg

    6 mg/kg

  • OsimertinibDrug

    dose escalation

    40mg

    80 mg

Study groups in NCT07535437
Study groupRoleWhat they receive
Cohort A (ivonescimab + Dato-DXd) Phase IAExperimental3 + 3 escalation (2 dose levels)
Receives: Drug: Ivonescimab; Drug: Dato-DXd
Cohort B (Ivonescimab + Osimertinib) Phase IBExperimental3 + 3 escalation (2 dose levels)
Receives: Drug: Ivonescimab; Drug: Osimertinib
Cohort A (ivonescimab + Dato-DXd) (Phase II)ExperimentalEvery 3 weeks
Receives: Drug: Ivonescimab; Drug: Dato-DXd
Cohort B (Ivonescimab + Osimertinib) (Phase II)ExperimentalIvonescimab every 3 weeks + Osimertinib daily
Receives: Drug: Ivonescimab; Drug: Osimertinib

What is being measured

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

  1. determine the maximum tolerated dose (MTD) (phase I)

    Three participants will be enrolled at starting dose level and assessed for dose limiting toxicities (DLTs) for 1 full cycle (21 days) in cohort A and 2 full cycles (42 days) for cohort B. Toxicity will be graded according to NCI CTCAE version 5.

    Measured: 1 year

  2. progression free survival (phase I)

    defined as the proportion of patients who remained alive and progression-free at 6 months) will be computed by Kaplan-Meier estimates and reduced to a standard sample proportion in the absence of censoring, with the follow-up starting at the initiation of therapy.

    Measured: 6 months

  3. measure objective response rate (ORR) (phase II)

    by RECIST v1.1

    Measured: 1 year

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 start9 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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07535437
Sponsor's protocol ID
25-366
Status last verified
Jul 2026
First submitted
10 Apr 2026
Last updated
13 Jul 2026
Results posted
No
Data monitoring committee
Yes
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 beginning 12 months after publication and for up to 36 months post publication. 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, Dato-DXd and Osimertinib 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 19 inclusion and 47 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 13 Jul 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 Helena Yu, MD (646-608-3912, yuh@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

determine the maximum tolerated dose (MTD) (phase I) (time frame: 1 year). The study lists 3 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 NCT07535437.

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 13 Jul 2026.

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