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

NCT07288034 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24507NCI-2025-09032P30CA033572
• Study Type: interventional
• Target: 535
• Locations: 1 country
• Sites: 13

Brief 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). 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.

Conditions

Lung Non-Small Cell Carcinoma; Stage IIIB Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  At pre-treatment and Cycle 2 Day 1 (blood only) (Cycle length = 21 days)

• Overall survival (OS)

  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

  Up to 3 years

• ctDNA complete response (CCR) rate

  Up to 3 years

• Objective response rate (ORR)

  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

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: Adagrasib; Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Interventions

Adagrasib DRUG

Given PO

Also known as: KRAS G12C Inhibitor MRTX849, Krazati, MRTX 849, MRTX-849, MRTX849

Arm B (adagrasib, bevacizumab)

Anti-PD1 Monoclonal Antibody BIOLOGICAL

Given PD1-based immunotherapy

Also known as: Anti-PD-1 Monoclonal Antibody

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1)

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm B (adagrasib, bevacizumab)

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1)

Biospecimen Collection PROCEDURE

Undergo blood, CSF, ascites and pleural fluid sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1); Arm A (tremelimumab, durvalumab); Arm B (adagrasib, bevacizumab)

Chemotherapy DRUG

Given chemotherapy

Also known as: Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1); Arm A (tremelimumab, durvalumab); Arm B (adagrasib, bevacizumab)

Durvalumab BIOLOGICAL

Given IV

Also known as: 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, MEDI4736

Arm A (tremelimumab, durvalumab)

Magnetic Resonance Imaging PROCEDURE

Undergo PET

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1); Arm A (tremelimumab, durvalumab); Arm B (adagrasib, bevacizumab)

Monitoring OTHER

Undergo monitoring

Also known as: monitor

Arm 1 (stop treatment, monitoring)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP 675, CP 675206, CP-675, CP-675,206, CP-675206, CP675, CP675206, Imjudo, Ticilimumab, Tremelimumab-actl

Arm A (tremelimumab, durvalumab)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1); Arm A (tremelimumab, durvalumab); Arm B (adagrasib, bevacizumab)

Surveillance BEHAVIORAL

Undergo close surveillance

Also known as: Epidemiology / Surveillance

Arm 3 (close surveillance)

Anti-PD-L1 Monoclonal Antibody BIOLOGICAL

Given PD-L1-based immunotherapy

Arm 1 (stop treatment, monitoring); Arm 2 (continue PD[L]1); Arm 3 (close surveillance); Arm 4 (PD[L]1)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (13)

CTCA at Western Regional Medical Center

Goodyear, Arizona, 85338, United States

RECRUITING

City of Hope Corona

Corona, California, 92882, United States

RECRUITING

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope Seacliff

Huntington Beach, California, 92648, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

City of Hope Antelope Valley

Lancaster, California, 93534, United States

RECRUITING

City of Hope at Long Beach Elm

Long Beach, California, 90813, United States

RECRUITING

City of Hope at Newport Beach Fashion Island

Newport Beach, California, 92660, United States

RECRUITING

City of Hope South Pasadena

South Pasadena, California, 91030, United States

RECRUITING

City of Hope South Bay

Torrance, California, 90503, United States

RECRUITING

City of Hope Upland

Upland, California, 91786, United States

RECRUITING

City of Hope Atlanta Cancer Center

Newnan, Georgia, 30265, United States

RECRUITING

City of Hope at Chicago

Zion, Illinois, 60099, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

adagrasib; spartalizumab; Bevacizumab; Immunoglobulin G; Disulfides; Biopsy; Specimen Handling; Drug Therapy; durvalumab; Magnetic Resonance Spectroscopy; tremelimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ravi Salgia, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Jyoti Malhotra [Co-PI], MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Part IA, Future Part IB to replace Part IA, and a non-randomized Part II

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: April 8, 2026
• Primary Completion (Estimated): October 8, 2028
• Study Completion (Estimated): October 8, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (13)