Ignite Creation Date:
2025-12-25 @ 2:31 AM
Ignite Modification Date:
2025-12-26 @ 1:07 AM
Study NCT ID:
NCT07288034
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-12-17
First Post:
2025-12-15
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
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
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
Immunotherapy Biomarker Collection for Metastatic NSCLC to Inform Adaptive Personalized Models Targeting Resistance (IMMUNO-BIOMAP)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.
I. 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:
I. 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:
I. 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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2025-09032 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 24507 | OTHER | City of Hope Medical Center | View | |
| P30CA033572 | NIH | None | https://reporter.nih.gov/quic… | View |