Phase 1 Study Of Izalontamab Brengitecan + Adagrasib In NSCLC - The IZA-A Trial

NCT07382726 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-1306NCI-2026-00662
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to test a combination of two drugs, Izalontamab Brengitecan (iza-bren) and Adagrasib, in patients with advanced KRAS G12C-mutant NSCLC that hasn't responded to other treatments. The purpose is to see if this combination works better than existing treatments for people whose cancer keeps growing despite KRAS G12C inhibitors.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W

EXPERIMENTAL

Adagrasib will be administered at 400mg PO BID continuously. Iza-bren will be administered IV on Day 1 and Day 8 (+3 days) in a 21-day cycle.

Drug: Adagrasib; Drug: Iza-bren

Interventions

Adagrasib DRUG

Given by mouth

Also known as: Krazati

Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W

Iza-bren DRUG

Given by IV

Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed diagnosis of NSCLC or NSCLC predominant histology.
• Patients must have a diagnosis of metastatic or locally advanced NSCLC not amenable to curative therapy
• Tumor must harbor a KRAS G12C mutation. Testing available through multigene NGS panels performed in the Molecular Diagnostics Laboratory in UT MD Anderson Cancer Center and can be performed using either tissue or blood assays. Use of standard of care (SOC) results are allowed to meet this requirement.
• Patients must have progressed on a prior KRAS G12C inhibitor as monotherapy or as combination therapy.
• Patients must have received at least one prior line of therapy and up to 3 prior lines of therapy.
• Patients must have measurable disease per RECIST v1.1.
• Age ≥18 years - no dosing or adverse event data are currently available on the use of izabren and adagrasib in patients \<18 years of age; children are excluded from this study.
• ECOG performance status 0 - 1.
• Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) discontinued at least 2 weeks before first dose date.
• Most recent radiation treatment discontinued at least 1 week prior to first dose date (includes brain radiation).
• Patients must have adequate organ and marrow function as defined below:
• Hemoglobin ≥9.0g/dL Absolute neutrophil count ≥1,500/mcL Platelets ≥100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) (if associated with liver metastases or Gilbert's disease, ≤ 3 x ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN (if associated with liver metastases, ≤ 5 x ULN) Creatinine ≤ 1.5 mg/dL or CrCl ≥ 45 mL/min (calculated using a validated prediction equation - e.g., Cockcroft-Gault, MDRD, or 24-hour urine CrCl)
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable.
• Patients with a history of hepatitis C virus (HCV) infection must have documentation of undetectable HCV viral load.
• Patients with treated brain metastases are eligible if patients are neurologically stable for at least 1 week prior to the first dose of study treatment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).

You may not qualify if:

• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) except for alopecia and parameters superseded by other eligibility criteria \[e.g., laboratory parameters\]).
• Patients who are receiving any other investigational agents.
• Patients with active untreated brain metastases or carcinomatous meningitis.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to adagrasib and iza-bren.
• Patients with prior history of pneumonitis or interstitial lung disease. Patients with prior history of radiation pneumonitis which was asymptomatic or resolved with steroid treatment, and without evidence of clinically active radiation pneumonitis are eligible.
• Human immunodeficiency virus (HIV)-infected patients. Those on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and actively breastfeeding woman due to concerns for teratogenicity and infant toxicity.
• Major surgery within 4 weeks prior to first dose of study treatment.
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications.
• Prolonged QTc interval (\>470 milliseconds for women and \>450 milliseconds for men), or immediate family or medical history of congenital Long QT Syndrome.
• History of stroke or transient ischemic attack within 6 months prior to first dose of study treatment.
• History of unstable angina, myocardial infarction, and symptomatic atrial fibrillation within 6 months prior to first dose of study treatment.
• Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

adagrasib

Condition Hierarchy (Ancestors)

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

Study Officials

• Marcelo V Negrao, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcelo V Negrao, MD

CONTACT

713-745-7943; mvnegrao@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 3, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 24, 2027
• Study Completion (Estimated): December 24, 2029
• Last Updated: February 20, 2026

Record last verified: 2026-01

Locations

US (1)