Ivonescimab Alone And With Carboplatin/Pemetrexed For NSCLC

NCT07405190 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-015
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to assess the efficacy of ivonescimab monotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations who have received prior targeted therapies and chemotherapy. This clinical trial also aims to assess the efficacy of ivonescimab plus carboplatin/pemetrexed chemotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations other than epidermal growth factor receptor mutations who have received prior targeted therapies but no chemotherapy. The main questions it aims to answer are:

• Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy shrink tumors in the clinical trial's patients?
• Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy effectively influence if the patients' cancer grows, how long the treatment takes to start working, how long the treatment keeps working after it first starts to help, how long the treatment keeps the cancer from getting worse, and overall survival of patients?
• How many patients receiving ivonescimab alone or together with carboplatin/pemetrexed chemotherapy will experience treatment-emergent, treatment-related, immune-related, and especially interesting side effects? Patients receiving ivonescimab alone will receive an intravenous infusion of ivonescimab every 3 weeks for up to 24 months. Patients receiving ivonescimab together with carboplatin/pemetrexed chemotherapy will receive separate intravenous infusions of ivonescimab, pemetrexed, and carboplatin every 3 weeks for 4 cycles (each cycle is 21 days). These patients will continue to receive infusions of ivonescimab and pemetrexed every 3 weeks for up to 24 total months.

Conditions

Lung Cancer (NSCLC); Lung Cancer Non-Small Cell Cancer (NSCLC); Lung Cancer (Non-Small Cell); Lung Cancer Non Small Cell; Genomic Alterations

Keywords

NSCLC; AGAs; lung cancer; non-small cell; chemotherapy; ivonescimab

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) of Ivonescimab Monotherapy

  The objective response rate (ORR) is defined as the number of patients with confirmed best overall response or complete response or partial response (PR) divided by the number of treated patients in the cohort. ORR will be measured per investigator. BOR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.

  Day 1 of cycle 1 (each cycle is 21 days) to disease progression, loss of follow-up, withdrawal of consent, study termination, or for up to 2 years from the day the last patient is enrolled, whichever occurs first.

• Objective Response Rate (ORR) of Ivonescimab plus Carboplatin/Pemetrexed

  The objective response rate (ORR) is defined as the number of patients with confirmed best overall response or complete response or partial response (PR) divided by the number of treated patients in the cohort. ORR will be measured per investigator. BOR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.

  Day 1 of cycle 1 (each cycle is 21 days) to disease progression, loss of follow-up, withdrawal of consent, study termination, or for up to 2 years from the day the last patient is enrolled, whichever occurs first.

Secondary Outcomes (14)

• Disease Control Rate (DCR) of Ivonescimab Monotherapy

  Day 1 of cycle 1 (each cycle is 21 days) to disease progression, loss of follow-up, withdrawal of consent, study termination, or for up to 2 years from the day the last patient is enrolled, whichever occurs first.

• Disease Control Rate (DCR) of Ivonescimab plus Carboplatin/Pemetrexed

  Day 1 of cycle 1 (each cycle is 21 days) to disease progression, loss of follow-up, withdrawal of consent, study termination, or for up to 2 years from the day the last patient is enrolled, whichever occurs first.

• Time to Response (TTR) of Ivonescimab Monotherapy

  Day 1 of cycle 1 (each cycle is 21 days) to the first documentation of complete or partial response for up to 2 years from the day the last patient is enrolled.

• Time to Response (TRR) of Ivonescimab plus Carboplatin/Pemetrexed

  Day 1 of cycle 1 (each cycle is 21 days) to the first documentation of complete or partial response for up to 2 years from the day the last patient is enrolled.

• Duration of Response (DOR) of Ivonescimab Monotherapy

  First day complete or partial response is recorded to the first day progressive disease is recorded or, if no progressive disease occurs, the date of last radiological assessment up to 2 years from the day the last patient is enrolled.

Study Arms (2)

Ivonescimab Monotherapy

EXPERIMENTAL

Patients with advanced/metastatic non-small cell lung cancer harboring actionable genomic alterations with disease progression after prior targeted therapies and chemotherapy will receive ivonescimab monotherapy. Ivonescimab will be administered at the pre-determined dose every 3 weeks on day 1 of each cycle (each cycle is 21 days) until disease progression, unacceptable toxicity, withdrawal of consent, or for up to 24 months, whichever occurs first.

Drug: Ivonescimab

Ivonescimab plus Carboplatin/Pemetrexed

EXPERIMENTAL

Patients with advanced/metastatic non-small cell lung cancer harboring actionable genomic alterations other than epidermal growth factor receptor mutations with disease progression after prior targeted therapies but no prior chemotherapy will receive ivonescimab, carboplatin, and pemetrexed. Ivonescimab will be administered at the pre-determined dose with the pre-determined doses of carboplatin and pemetrexed on day 1 of the first 4 treatment cycles (each cycle is 21 days) or until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first. Patients who have stable disease or response after the first 4 treatment cycles will continue to receive pre-determined doses of ivonescimab and pemetrexed every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or for up to 24 months, whichever occurs first.

Drug: Ivonescimab; Drug: carboplatin; Drug: pemetrexed

Interventions

Ivonescimab DRUG

Ivonescimab is a specially engineered antibody that can attach to both PD-1 and VEGF-A.

Also known as: AK112, SMT112

Ivonescimab Monotherapy; Ivonescimab plus Carboplatin/Pemetrexed

carboplatin DRUG

Carboplatin is a type of chemotherapy drug that contains a special form of platinum.

Also known as: Paraplatin

Ivonescimab plus Carboplatin/Pemetrexed

pemetrexed DRUG

Pemetrexed is a type of chemotherapy drug that works by blocking specific substances, called folates, that cancer cells need to grow and multiply.

Also known as: Alimta

Ivonescimab plus Carboplatin/Pemetrexed

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 advanced or metastatic non-squamous NSCLC not amenable to curative resection or radiation.
• AGA requirements as follows:
• Ivonescimab monotherapy: Tumor harboring classical EGFR sensitizing mutation (i.e., L858R, exon 19 deletion), or ALK, ROS1, RET, or NTRK1-3 fusion, per local testing. Note: The number of patients with EGFR mutation-positive NSCLC enrolled will be capped at maximum of 10 (in order to ensure the assessment of non-EGFR disease subsets). Ivonescimab plus carboplatin/pemetrexed: Tumor harboring ALK, ROS1, RET, or NTRK1-3 fusion, per local testing.
• Prior therapy requirements as follows:
• a. Prior genotype-specific standard-of-care targeted therapy must have included at least one genotype-appropriate TKI(s) specified below: i. EGFR sensitizing mutation: a third-generation EGFR TKI such as osimertinib or lazertinib ii. ALK fusion: a third- or fourth-generation ALK TKI such as lorlatinib or neladalkib (NVL-655) iii. ROS1 fusion: crizotinib, entrectinib, repotrectinib, or taletrectinib iv. RET fusion: selpercatinib or pralsetinib v. NTRK1-3 fusion: entrectinib, larotrectinib, or repotrectinib Ivonescimab monotherapy: Must have received platinum/pemetrexed chemotherapy. No limitations on the number of prior lines of systemic therapy including the number of lines of chemotherapy or TKI(s). Ivonescimab plus carboplatin/pemetrexed: May not have received any prior chemotherapy. No limitations on the number of prior TKI(s).
• At least 1 measurable lesion as assessed by investigator per the RECIST v1.1 criteria for both cohorts.
• Participants must be willing to undergo the mandatory pre-treatment and post-progression tissue biopsies. If archival pre-treatment tissue is available from within 6 months of study enrollment, with no new intervening systemic therapy since the biopsy, a repeat pre-treatment biopsy may be omitted upon discussion with the principal investigator. On-treatment tissue biopsy (obtained within 7 days prior to Cycle 2 Day 1) will be mandatory for patients in Cohort 1 and optional for patients in Cohort 2. In select cases, if medically deemed unsafe/not feasible, exception may be granted upon discussion with the principal investigator.
• Clinically asymptomatic treated or untreated brain metastases are allowed if they have not required increasing doses of steroids within 2 weeks prior to study entry for CNS symptoms.
• Age ≥18 years old.
• ECOG performance status of 0 or 1.
• 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 (Cohorts 1 and 2) or estimated glomerular filtration rate (eGFR) value ≥ 60 mL/min (for Cohort 1) or ≥30 mL/min (for Cohort 2) using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) 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)
• × ULN; for patients with liver metastases, AST and ALT ≤ 5 × ULN d. Coagulation: prothrombin time (PT) or international normalized ratio (INR)
• 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 for at least one month prior to study enrollment.
• Female patients of childbearing age must have negative serum pregnancy test results before first ivonescimab drug dose 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.

You may not qualify if:

• Participants previously treated with immune checkpoint inhibitors or other T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents.
• Major surgical procedures or serious trauma within 4 weeks prior to first ivonescimab dose or plans for major surgical procedures within 4 weeks after the first ivonescimab dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to first ivonescimab dose.
• History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to first ivonescimab dose, 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 first ivonescimab dose is not allowed; stability of anti-coagulation dosing will be defined by remaining on the same dose for at least one month prior to study enrollment.
• 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.
• 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 first ivonescimab dose; however, the following will be allowed:
• 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.
• History of major diseases before first ivonescimab dose, 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 6 months prior to first ivonescimab dose, 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 before first ivonescimab dose
• 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) 6.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to first ivonescimab dose

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Summit Therapeutics: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Jessics J Lin, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica J. Lin, MD

CONTACT

617-724-4000; jjlin1@partners.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 12, 2026
• Study Start (Estimated): August 4, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovation team at http://www.partners.org/innovation

Locations

US (3)