A Study of Ivonescimab in Combination With Dato-DXd or Osimertinib in People With Non-Small Cell Lung Cancer
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
1 other identifier
interventional
66
1 country
7
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 nonsmall-cell-lung-cancer
Started Apr 2026
Shorter than P25 for phase_1 nonsmall-cell-lung-cancer
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 9, 2026
CompletedFirst Submitted
Initial submission to the registry
April 10, 2026
CompletedFirst Posted
Study publicly available on registry
April 17, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2028
April 21, 2026
April 1, 2026
2 years
April 10, 2026
April 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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.
1 year
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.
6 months
measure objective response rate (ORR) (phase II)
by RECIST v1.1
1 year
Study Arms (4)
Cohort A (ivonescimab + Dato-DXd) Phase IA
EXPERIMENTAL3 + 3 escalation (2 dose levels)
Cohort B (Ivonescimab + Osimertinib) Phase IB
EXPERIMENTAL3 + 3 escalation (2 dose levels)
Cohort A (ivonescimab + Dato-DXd) (Phase II)
EXPERIMENTALEvery 3 weeks
Cohort B (Ivonescimab + Osimertinib) (Phase II)
EXPERIMENTALIvonescimab every 3 weeks + Osimertinib daily
Interventions
20 mg/kg
dose escalation 4 mg/kg 6 mg/kg
dose escalation 40mg 80 mg
Eligibility Criteria
You may qualify if:
- 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
- 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)
- +4 more criteria
You may not qualify if:
- 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)
- 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.
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Summit Therapeuticscollaborator
Study Sites (7)
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (All Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (All Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (All Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (All Protocol Activities)
Uniondale, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Helena Yu, MD
Memorial Sloan Kettering Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2026
First Posted
April 17, 2026
Study Start
April 9, 2026
Primary Completion (Estimated)
April 1, 2028
Study Completion (Estimated)
April 1, 2028
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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.