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

NCT07535463 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 26-021
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 7

Brief 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). 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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Ivonescimab; Stereotactic Radiosurgery; 26-021

Outcome Measures

Primary Outcomes (2)

• identify the Recommended Phase 2 Dose (RPD2)

  per NCI CTCAE version 5.0 criteria

  21 days

• intracranial progression-free survival (iPFS),

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

  3 months

Study Arms (1)

Ivonescimab, Chemotherapy, and Stereotactic Radiosurgery

EXPERIMENTAL

In 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.

Drug: Ivonescimab; Radiation: Stereotactic Radiosurgery

Interventions

Ivonescimab DRUG

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.

Ivonescimab, Chemotherapy, and Stereotactic Radiosurgery

Stereotactic Radiosurgery RADIATION

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

Ivonescimab, Chemotherapy, and Stereotactic Radiosurgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• a. 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:
• 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, 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Summit Therapeutics: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Rockville Centre, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Luke Pike, M.D., PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luke Pike, MD, PhD

CONTACT

212-639-8157; pikel@mskcc.org

Mark Awad, M.D., PhD

CONTACT

646-608-2928

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, phase I/II trial.

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 17, 2026
• Study Start: April 10, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)