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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Adagrasib — DRUG
  Given PO
• Anti-PD-L1 Monoclonal Antibody — BIOLOGICAL
  Given PD-L1-based immunotherapy
• Anti-PD1 Monoclonal Antibody — BIOLOGICAL
  Given PD1-based immunotherapy
• Bevacizumab — BIOLOGICAL
  Given IV
• Biopsy Procedure — PROCEDURE
  Undergo tumor biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood, CSF, ascites and pleural fluid sample collection
• Chemotherapy — DRUG
  Given chemotherapy
• Computed Tomography — PROCEDURE
  Undergo CT
• Durvalumab — BIOLOGICAL
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo PET
• Monitoring — OTHER
  Undergo monitoring
• Positron Emission Tomography — PROCEDURE
  Undergo PET
• Surveillance — BEHAVIORAL
  Undergo close surveillance
• Tremelimumab — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Apr 8, 2026

Status verified

Apr 2026

Primary completion

Oct 8, 2028

Completion

Oct 8, 2028

Study Design

Enrollment

535 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

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

Primary Outcome Measure

Progression-free survival (PFS) during first-line treatment (Part I) [ Time Frame: From the start of randomization to disease progression or death from any cause, whichever occurs first, assessed up to 3 years ]

Locations (13)

Find similar trials in Goodyear, AZ

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