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

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

Interventions

DRUG

Adagrasib

Given PO

BIOLOGICAL

Anti-PD-L1 Monoclonal Antibody

Given PD-L1-based immunotherapy

BIOLOGICAL

Anti-PD1 Monoclonal Antibody

Given PD1-based immunotherapy

BIOLOGICAL

Bevacizumab

Given IV

PROCEDURE

Biopsy Procedure

Undergo tumor biopsy

PROCEDURE

Biospecimen Collection

Undergo blood, CSF, ascites and pleural fluid sample collection

DRUG

Chemotherapy

Given chemotherapy

PROCEDURE

Computed Tomography

Undergo CT

BIOLOGICAL

Durvalumab

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo PET

OTHER

Monitoring

Undergo monitoring

PROCEDURE

Positron Emission Tomography

Undergo PET

BEHAVIORAL

Surveillance

Undergo close surveillance

BIOLOGICAL

Tremelimumab

Given IV

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Ravi Salgia, MD · City of Hope Medical Center

• Jyoti Malhotra [Co-PI], MD · City of Hope Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-08

Primary Completion

2028-10-08

Completion

2028-10-08

FDA Drug

Yes

Countries

• United States

Study Locations