Non-small Cell Lung CancerPhase 1NCT07382726
Phase 1 Study Of Izalontamab Brengitecan + Adagrasib In NSCLC - The IZA-A Trial
A Phase 1 study testing Adagrasib and Iza-bren in people with Non-small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. 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?
- Adagrasib and Iza-bren
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2026to 24 Dec 2029
- Phase
- Phase 1
- 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
- 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.
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- 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).
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
- Because adagrasib and iza-bren are known to be teratogenic, women of child-bearing potential (WCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 (men) and 7 (WCBP) months after completion of study treatment administration. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients less than 55 years of age unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of study treatment administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Marcelo V Negrao, MD, 713-745-7943, mvnegrao@mdanderson.org
Marcelo V Negrao, MD
About this study
Official title: Combination Of Izalontamab Brengitecan And Adagrasib In Advanced KRAS G12Ci-Refractory Non-Small Cell Lung Cancer - The IZA-A Trial
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.
Read the detailed description
Primary Objective:
To evaluate the safety and tolerability of iza-bren in combination with adagrasib for treatment of KRAS G12C-mutant NSCLC patients that progressed on KRAS G12C inhibitors.
Secondary Objectives:
- To evaluate the preliminary efficacy of iza-bren in combination with adagrasib for treatment of KRAS G12C-mutant NSCLC patients that progressed on KRAS G12C inhibitors.
- To evaluate the pharmacokinetics of iza-bren upon combination treatment with adagrasib.
- To evaluate immunogenicity against iza-bren upon combination treatment with adagrasib.
- To evaluate the incidence of anti-drug antibody (ADA) formation to Iza-bren when it is administered in combination with adagrasib, and to assess the potential effect of ADA on PK, PD and safety.
- To evaluate EGFR and HER3 tumor expression as determinants of clinical outcomes to study regimen.
- To evaluate circulating tumor DNA (ctDNA) as a determinant of clinical outcome to study regimen.
- To evaluate mechanisms of resistance to study regimen.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Adagrasib, Iza-bren
- 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.
AdagrasibDrug
Also called Krazati
Given by mouth
Iza-brenDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Adagrasib; Drug: Iza-bren |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2026
- Study start15 May 2026
- Primary completion24 Dec 2027 (estimated)
- Study completion24 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marcelo V Negrao, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07382726
- Sponsor's protocol ID
- 2025-1306
- Other IDs
- NCI-2026-00662
- Status last verified
- Aug 2026
- First submitted
- 26 Jan 2026
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Of Izalontamab Brengitecan And Adagrasib In Advanced KRAS G12Ci-Refractory Non-Small Cell Lung Cancer - The IZA-A Trial
- ClinicalTrials.gov ID
- NCT07382726
- Acronym / sponsor ID
- 2025-1306
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 15 May 2026 (actual)
- Primary completion
- 24 Dec 2027 (estimated)
- Study completion
- 24 Dec 2029 (estimated)
- First posted
- 3 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary Objective:
To evaluate the safety and tolerability of iza-bren in combination with adagrasib for treatment of KRAS G12C-mutant NSCLC patients that progressed on KRAS G12C inhibitors.
Secondary Objectives:
- To evaluate the preliminary efficacy of iza-bren in combination with adagrasib for treatment of KRAS G12C-mutant NSCLC patients that progressed on KRAS G12C inhibitors.
- To evaluate the pharmacokinetics of iza-bren upon combination treatment with adagrasib.
- To evaluate immunogenicity against iza-bren upon combination treatment with adagrasib.
- To evaluate the incidence of anti-drug antibody (ADA) formation to Iza-bren when it is administered in combination with adagrasib, and to assess the potential effect of ADA on PK, PD and safety.
- To evaluate EGFR and HER3 tumor expression as determinants of clinical outcomes to study regimen.
- To evaluate circulating tumor DNA (ctDNA) as a determinant of clinical outcome to study regimen.
- To evaluate mechanisms of resistance to study regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W | Experimental | Drug: Adagrasib, Drug: Iza-brenAdagrasib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdagrasibAlso: KrazatiGiven by mouth | Drug | Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W |
| Iza-brenGiven by IV | Drug | Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W |
Primary outcome
Safety and Adverse Events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marcelo V Negrao, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adagrasib and Iza-bren in people with Non-small Cell Lung Cancer, run by M.D. Anderson Cancer Center at 1 site 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 25 inclusion and 14 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 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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 Marcelo V Negrao, MD (713-745-7943, mvnegrao@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Aug 2026.