Lung Non-Small Cell CarcinomaPhase 2NCT07288034
Immunotherapy Biomarkers to Predict First-line PD(L)1-based Immunotherapy Response and Selection of Second-line Treatment in Stage IIIB-IV Non-small Cell Lung Cancer, IMMUNO-BIOMAP Trial
A Phase 2 study testing Adagrasib, Anti-PD-L1 Monoclonal Antibody and Anti-PD1 Monoclonal Antibody in people with Lung Non-Small Cell Carcinoma and Stage IIIB Lung Cancer AJCC v8, run by City of Hope Medical Center at 13 sites in United States.
Trial summary
This phase II trial tests the impact of biomarkers in predicting initial treatment (first-line) PD1 or PD-L1 (PD[L]-1)-based immunotherapy response and in selecting second-line treatment in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8
- What is being tested?
- Adagrasib, Anti-PD-L1 Monoclonal Antibody and Anti-PD1 Monoclonal Antibody
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 535 participants
- Where
- 13 sitesUnited States
- Study dates
- 1 May 2026to 8 Oct 2028
- Phase
- Phase 2
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
- Documented informed consent of the participant and/or legally authorized representative. (Adult patients lacking capacity to consent may participate if they have a caretaker that could ensure compliance.)
- Participants must have either A) HopeSeq or Tempus molecular testing results reported within 3 months prior to enrollment or currently in process OR B) archival or new biopsy tissue available (to be sent to Tempus). Acceptable sample types include: two formalin-fixed paraffin-embedded (FFPE) tissue core biopsies, or two 25um sections of 5-10mm^2 tissue, or 15-20 unstained slides at 10um thickness (a minimum of 10 unstained slides must be provided)
- Agreement to blood collection for ctDNA research
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Histologically confirmed stage IIIB or IV NSCLC
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- Absence of sensitizing EGFR mutation or ALK/ROS1 alteration
- Scheduled to begin treatment with a Food and Drug Administration (FDA) approved PD1/PDL1 antibody with or without chemotherapy. Participants who have already started treatment with anti-PD1/PDL1 in this setting may enroll if they have only received up to 4 cycles of treatment so far. Patients who have received PD1/PDL1 antibody for early-stage NSCLC are allowed to enroll if they completed the therapy at least 6 months before starting trial therapy
- Measurable disease by RECIST version (v) 1.1
- Absolute neutrophil count (ANC) ≥ 1,500/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment
- Platelets ≥ 100,000/mm^3
- NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
- Hemoglobin ≥ 9g/dL
- NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
- Alanine aminotransferase (ALT) ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
- Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
- If seropositive for HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
- PART II: Documented informed consent (for Part II) of the participant and/or legally authorized representative.
- Assent, when appropriate, will be obtained per institutional guidelines
- PART II: ECOG ≤ 2
- PART II: Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
- PART II: ANC ≥ 1,500/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment
- PART II: Platelets ≥ 100,000/mm^3
- NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
- PART II: Hemoglobin ≥ 9g/dL
- NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
- PART II: Total bilirubin ≤ 1.5 x ULN
- PART II: AST ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
- PART II: ALT ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
- PART II: Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
Who cannot join
- Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement
- Patients with a condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) within 7 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Radiation therapy within 7 days prior to day 1 of protocol therapy
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association [NYHA class] ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication
- Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs
- Symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have 1) previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug OR 2) untreated brain metastases that are asymptomatic and stable
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- Prior history of interstitial lung disease (ILD) or non-infectious pneumonitis requiring high-dose glucocorticoids
- Active infection requiring antibiotics
- Other active malignancy. Patients with concurrent malignancy other than non-melanoma skin cancer are not eligible for this trial due to potential confounding of the ctDNA results
- Females only: Pregnant or breastfeeding
- PART II: Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement
- PART II: Radiation therapy within 7 days prior to day 1 of protocol therapy
- PART II ARM A ONLY: Patients with a condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) within 7 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- PART II ARM A ONLY: Patients with prior history of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) treatment
- PART II ARM B ONLY: Patients with prior history of KRAS G12C inhibitors
- PART II: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication
- PART II ARM A ONLY: Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs
- PART II ARM B ONLY: Grade ≥ 2 proteinuria as demonstrated by ≥ 2+ protein and ≥ 1.0 g of protein with 24-hour urine collection (patients found to have ≥ 2+ protein on dipstick urinalysis must have 24-hour urine collection and demonstrate < 1g of protein in 24 hours in order to be eligible for treatment)
- PART II: Clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have 1) previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroid medication for 1 week prior to the first dose of study drug and have completed radiation 2 weeks prior to the first dose of study drug OR 2) untreated brain metastases that are asymptomatic and stable
- PART II: Clinically significant uncontrolled illness
- PART II: Active infection requiring antibiotics
- PART II: Other active malignancy
- PART II FEMALES ONLY: Pregnant or breastfeeding
- PART II: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
City of Hope Corona
Corona, California, 92882
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope Medical Center
Duarte, California, 91010
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
CTCA at Western Regional Medical Center
Goodyear, Arizona, 85338
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope Seacliff
Huntington Beach, California, 92648
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope at Irvine Lennar
Irvine, California, 92618
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope Antelope Valley
Lancaster, California, 93534
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope at Long Beach Elm
Long Beach, California, 90813
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope Atlanta Cancer Center
Newnan, Georgia, 30265
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope at Newport Beach Fashion Island
Newport Beach, California, 92660
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope South Pasadena
South Pasadena, California, 91030
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope South Bay
Torrance, California, 90503
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope Upland
Upland, California, 91786
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
- Recruiting
City of Hope at Chicago
Zion, Illinois, 60099
Ravi Salgia, 626-218-9200, rsalgia@coh.org
Ravi Salgia
About this study
Official title: Immunotherapy Biomarker Collection for Metastatic NSCLC to Inform Adaptive Personalized Models Targeting Resistance (IMMUNO-BIOMAP)
This phase II trial tests the impact of biomarkers in predicting initial treatment (first-line) PD1 or PD-L1 (PD[L]-1)-based immunotherapy response and in selecting second-line treatment in patients with stage IIIB-IV non-small cell lung cancer (NSCLC). Response and survival rates in advanced stage NSCLC, unlike other cancers, rely on response to first-line therapy. Immunotherapy with PD(L)1-based therapy, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. While immunotherapy has improved survival rate, the prognosis remains poor with most patients receiving chemotherapy after immunotherapy. Many types of tumors tend to lose cells or release different types of cellular products including their deoxyribonucleic acid (DNA) which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. The first part of this trial, studying samples of blood and tissue in the laboratory from patients receiving immunotherapy may help doctors learn more about the effects PD(L)1-based therapy on cells. It may also help doctors understand how well patients respond to treatment and may help develop new individualized treatment strategies. The second part of this trial also tests the effect of second-line immunotherapy, such as tremelimumab and durvalumab or adagrasib and bevacizumab, in treating patients with NSCLC with specific genetic mutations that is growing, spreading or getting worse (progressive). Tremelimumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adagrasib, a type of targeted therapy, may stop the growth of tumor cells by blocking a protein needed for tumor cell growth and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving second-line immunotherapy, tremelimumab and durvalumab or adagrasib with bevacizumab, may be safe, tolerable, and/or effective in treating patients with stage IIIB/IV NSCLC with specific genetic mutations.
Read the detailed description
PRIMARY OBJECTIVES:
- Develop biomarker(s) that predicts for first-line treatment failure of immunotherapy (Part I).
II. Evaluate different strategies for treatment duration for patients without early treatment failure based on ctDNA (Part I).
III. Evaluate second-line progression-free survival (PFS) for biomarker-specific treatment decisions compared to historical controls (Part II).
SECONDARY OBJECTIVES:
- Evaluate different ctDNA-guided treatment decisions on overall survival based on arm.
II. Summarize the relationship between ctDNA changes and Response Evaluation Criteria in Solid Tumors (RECIST) response throughout the trial.
III. To describe the incidence and severity of adverse events by treatment arm. IV. Demonstrate the feasibility of an adaptive design employing both dynamic treatment regimen and biomarker-specific directed therapy.
EXPLORATORY OBJECTIVE:
- Use data from ctDNA and tissue multi-omics analysis for reverse translational modeling for mechanisms of resistance to immunotherapy using ARTEMIS.
OUTLINE:
PART IA (INITIAL DISCOVERY COHORT): Patients receive physician's choice of PD(L)1-based therapy every 3 weeks (Q3W) with or without chemotherapy for up to 12-24 months per standard of care.
Patients who complete at least 12 months of PD(L)1 (but do not exceed 24 months) and achieve complete response (CR), stable disease (SD), or partial response (PR) on imaging, as well as ctDNA complete response (CCR) for at least 6 months are randomized to Arms 1 or 2.
ARM 1: After at least 12 months of treatment, patients discontinue PD(L)1 therapy and undergo monitoring. Patients who develop positive ctDNA without PD resume PD(L)1 on study.
ARM 2: After at least 12 months of treatment, patients continue PD(L)1 therapy for up to a total of 24 months from starting immunotherapy the absence of disease progression or unacceptable toxicity.
Patients who complete 24 months of immunotherapy and achieve CR, SD, or PR on imaging, but not CCR and who were not candidates for Arms 1 and 2 are randomized to Arms 3 or 4.
ARM 3: After at least 24 months of treatment, patients discontinue PD(L)1 therapy and undergo close surveillance on study.
ARM 4: After at least 24 months of treatment, patients continue to receive PD(L)1 therapy until radiographic progression or unacceptable toxicity.
PART IB (IMPLEMENTATION COHORT): Patients participate in a future implementation cohort utilizing the findings from Part 1A.
PART II (POST-PROGRESSION COHORT): Patients who experience radiographic progression on Part I are assigned to 1 of 3 arms. Patients with STK11 or KEAP1 mutations are assigned to Arm A and patients with KRAS G12C mutations are assigned to Arm B. Patients assigned to Arm X will be added based on the funding grant technical area 1 (TA1-Therapy Recommendation Techniques).
ARM A: Patients receive tremelimumab intravenously (IV) over 1 hour on day 1 of cycles 1-4 and on day 1 of cycle 6, as well as durvalumab IV over 1 hour of each cycle. Cycles repeat every 21 days for cycles 1-5 and then starting with cycle 6, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive adagrasib orally (PO) twice daily (BID) on days 1-21 and bevacizumab IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM X: Patients participate in future interventions to be added based on the funding grant TA1-Therapy Recommendation Techniques.
Patients in both Parts also undergo blood sample collection, and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) throughout the study. Additionally, patients may undergo cerebrospinal fluid (CSF), ascites and pleural fluid sample collection during routine care throughout the study. Patients in Part 1 only undergo a tumor biopsy throughout the study.
After completion of study treatment, patients are followed up at 30 days, every 3 months within 1 year of starting treatment, then every 6 months for up to 2 years.
- Conditions
- Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8
- Being tested
- Adagrasib, Anti-PD-L1 Monoclonal Antibody, Anti-PD1 Monoclonal Antibody, Bevacizumab, Biopsy Procedure
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdagrasibDrug
Also called KRAS G12C Inhibitor MRTX849, Krazati, MRTX 849, MRTX-849
Given PO
Anti-PD-L1 Monoclonal AntibodyBiological
Given PD-L1-based immunotherapy
Anti-PD1 Monoclonal AntibodyBiological
Also called Anti-PD-1 Monoclonal Antibody
Given PD1-based immunotherapy
BevacizumabBiological
Also called ABP 215, ABP-215, ABP215, Alymsys
Given IV
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood, CSF, ascites and pleural fluid sample collection
ChemotherapyDrug
Also called Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General
Given chemotherapy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
DurvalumabBiological
Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo PET
MonitoringOther
Also called monitor
Undergo monitoring
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET
SurveillanceBehavioural
Also called Epidemiology / Surveillance
Undergo close surveillance
TremelimumabBiological
Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206, CP-675
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (stop treatment, monitoring) | Experimental | Patients receive physician's choice of PD(L)1-based therapy Q3W with or without chemotherapy for up to 12-24 months per standard of care. After at least 12 months of treatment, patients discontinue PD(L)1 therapy and undergo monitoring. Patients who develop positive ctDNA without PD resume PD(L)1 on study. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care and tumor biopsy throughout the study. Receives: Biological: Anti-PD-L1 Monoclonal Antibody; Biological: Anti-PD1 Monoclonal Antibody; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Monitoring; Procedure: Positron Emission Tomography |
| Arm 2 (continue PD[L]1) | Experimental | Patients receive physician's choice of PD(L)1-based therapy Q3W with or without chemotherapy for up to 12-24 months per standard of care. After at least 12 months of treatment, patients continue PD(L)1 therapy for up to a total of 24 months from starting immunotherapy in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care and tumor biopsy throughout the study. Receives: Biological: Anti-PD-L1 Monoclonal Antibody; Biological: Anti-PD1 Monoclonal Antibody; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography |
| Arm 3 (close surveillance) | Experimental | Patients receive physician's choice of PD(L)1-based therapy Q3W with or without chemotherapy for up to 12-24 months per standard of care. After at least 24 months of treatment, patients discontinue PD(L)1 therapy and undergo close surveillance on study. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care and tumor biopsy throughout the study. Receives: Biological: Anti-PD-L1 Monoclonal Antibody; Biological: Anti-PD1 Monoclonal Antibody; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Behavioral: Surveillance |
| Arm 4 (PD[L]1) | Experimental | Patients receive physician's choice of PD(L)1-based therapy Q3W with or without chemotherapy for up to 12-24 months per standard of care. After at least 24 months of treatment, patients continue to receive PD(L)1 therapy until radiographic progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care and tumor biopsy throughout the study. Receives: Biological: Anti-PD-L1 Monoclonal Antibody; Biological: Anti-PD1 Monoclonal Antibody; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Chemotherapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography |
| Arm A (tremelimumab, durvalumab) | Experimental | Patients receive tremelimumab IV over 1 hour on day 1 of cycles 1-4 and on day 1 of cycle 6 as well as durvalumab IV over 1 hour of each cycle. Cycles repeat every 21 days for cycles 1-5 and then starting with cycle 6, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care throughout the study. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Biological: Tremelimumab |
| Arm B (adagrasib, bevacizumab) | Experimental | Patients receive adagrasib PO BID on days 1-21 and bevacizumab IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET throughout the study. Additionally, patients may undergo CSF, ascites and pleural fluid sample collection during routine care throughout the study. Receives: Drug: Adagrasib; Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) during first-line treatment (Part I)
Will be estimated using the Kaplan-Meier (KM) method. Comparisons across treatment arms will be performed using stratified log-rank tests and Cox proportional hazards models, with assessment of the proportional-hazards assumption and exploration of time-dependent hazard ratios. Dynamic treatment regimen (DTR)-specific PFS will also be estimated using inverse probability weighting (IPW) to account for multiple randomizations and treatment adaptations.
Measured: From the start of randomization to disease progression or death from any cause, whichever occurs first, assessed up to 3 years
PFS by arm for second-line treatment (Part II)
Will be estimated using the KM method. Comparisons across treatment arms will be performed using stratified log-rank tests and Cox proportional hazards models, with assessment of the proportional-hazards assumption and exploration of time-dependent hazard ratios. DTR-specific PFS will also be estimated using IPW to account for multiple randomizations and treatment adaptations.
Measured: From the start of treatment to disease progression or death from any cause, whichever occurs first, assessed up to 3 years
Secondary outcomes (9)
Development and testing of biomarkers predictive of early response to immunotherapy
Will include, but not limited to, blood based, tissue-based and imaging-based biomarkers.
Measured: At pre-treatment and Cycle 2 Day 1 (blood only) (Cycle length = 21 days)
Overall survival (OS)
Will be evaluated by arm. Will be estimated using the KM method. Comparisons across treatment arms will be performed using stratified log-rank tests and Cox proportional hazards models, with assessment of the proportional-hazards assumption and exploration of time-dependent hazard ratios. DTR-specific OS will also be estimated using IPW to account for multiple randomizations and treatment adaptations.
Measured: From randomization (by arm and from start of first-line treatment) to death due to any cause, assessed up to 3 years
Circulating tumor deoxyribonucleic acid (ctDNA) level
Joint modeling approaches will be applied, combining mixed-effects models for ctDNA trajectories with survival models for PFS or OS. All stratified efficacy analyses will incorporate randomization stratification factors.
Measured: Up to 3 years
ctDNA complete response (CCR) rate
Will be summarized by treatment sequence. Logistic regression models will evaluate associations between CCR and baseline covariates.
Measured: Up to 3 years
Objective response rate (ORR)
Will be defined as rate of participants achieving confirmed complete response or partial response, as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version (v) 1.1. ORR point estimates and 95% confidence intervals will be calculated using Clopper-Pearson methods, and logistic regression modeling will assess associations between treatment and objective response.
Measured: From start of the study treatment to disease progression or death due to any cause prior to receiving another therapy, whichever occurs first, assessed up to 3 years
Duration of response
Measured: From the time a response is experienced to progression or death, assessed up to 3 years
Incidence of, causality, and outcome of adverse events (AEs)
AEs will described using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. Will be summarized with descriptive statistics: mean, median, standard deviation, minimum, and maximum for continuous variables, and frequencies and percentages for categorical variables.
Measured: Up to 30 days after last dose of study treatment
Incidence of, causality, and outcome of serious AEs
AEs will be assessed as defined by NCI-CTCAE v 5.0. Will be summarized with descriptive statistics: mean, median, standard deviation, minimum, and maximum for continuous variables, and frequencies and percentages for categorical variables.
Measured: Up to 30 days after last dose of study treatment
Changes in vital signs and laboratory values
Will be summarized with descriptive statistics: mean, median, standard deviation, minimum, and maximum for continuous variables, and frequencies and percentages for categorical variables.
Measured: Up to 30 days after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2025
- Study start1 May 2026
- Primary completion8 Oct 2028 (estimated)
- Study completion8 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Non-Small Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Randomized Part IA, Future Part IB to replace Part IA, and a non-randomized Part II
- Masking
- None (open label)
- Enrolment
- 535 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ravi Salgia, MD, Principal investigator, City of Hope Medical CenterJyoti Malhotra [Co-PI], MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07288034
- Sponsor's protocol ID
- 24507
- Other IDs
- NCI-2025-09032, 24507, P30CA033572
- Status last verified
- Oct 2026
- First submitted
- 15 Dec 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No