Immunotherapy Biomarkers for Non-Small Cell Lung Cancer

Not yet recruiting at 12 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: PD1/PDL1 antibodies

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Cardiovascular disease, Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 27

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain biomarkers (biological signs) can predict responses to different immunotherapies in people with advanced non-small cell lung cancer. Researchers are testing whether biomarkers can guide the choice of first-line and second-line treatments, such as tremelimumab and durvalumab (both immunotherapy drugs) or adagrasib (a targeted therapy drug) and bevacizumab, to improve outcomes. The trial targets individuals with stage IIIB-IV non-small cell lung cancer who are beginning or have recently started immunotherapy. Participants must have measurable disease and lack specific genetic mutations like EGFR or ALK. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using tremelimumab and durvalumab together to treat non-small cell lung cancer (NSCLC) is generally safe. Studies have found that most side effects are mild. This combination also helps the immune system fight cancer.

For the combination of adagrasib and bevacizumab, data indicates that most patients experience mild side effects, though some may face more serious ones. Despite this, the treatment effectively slows cancer growth.

Overall, researchers are studying these treatments to ensure they are safe and effective for people with advanced NSCLC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they offer innovative approaches compared to current standards like chemotherapy and first-line immunotherapy with anti-PD-1/PD-L1 antibodies. Adagrasib, combined with bevacizumab, targets KRAS mutations, a frequent driver in lung cancer, potentially offering a more personalized approach. The use of tremelimumab alongside durvalumab introduces a dual checkpoint blockade, which might enhance the immune system's ability to attack cancer cells more effectively. These strategies provide hope for improved outcomes and personalized therapeutic options in a condition that traditionally has limited treatment successes.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that PD(L)1-based immunotherapy can help the immune system combat non-small cell lung cancer (NSCLC), improving survival rates. In this trial, some participants will receive treatments like durvalumab, which have increased overall survival, with some patients benefiting for extended periods. Another arm of the trial will test the combination of tremelimumab and durvalumab, which has shown promise in extending the time patients live without disease progression. In a separate arm, adagrasib has demonstrated a 42.9% response rate and has helped patients with certain genetic mutations live longer without disease progression. Bevacizumab, when combined with treatments like adagrasib in this trial, can slow tumor growth by preventing the formation of blood vessels that tumors need. Together, these treatments offer hope for better outcomes in advanced NSCLC. ^{1 6 7 8 9}

Who Is on the Research Team?

Ravi Salgia

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (stages IIIB-IV). Participants must have specific genetic mutations in their tumors and be candidates for first-line PD(L)1-based immunotherapy. They should not have received prior treatments that would affect the study's outcome.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1,500/mm^3

PART II: ALT ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)

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

Exclusion Criteria

I have previously been treated with CTLA-4 inhibitors.

I haven't had major surgery in the last 4 weeks, except for minor procedures like port placement.

I haven't taken high-dose steroids or immunosuppressants recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive PD(L)1-based therapy every 3 weeks with or without chemotherapy for up to 12-24 months

12-24 months

Every 3 weeks

Post-Progression Treatment

Patients with specific genetic mutations receive second-line treatments such as tremelimumab, durvalumab, adagrasib, and bevacizumab

Up to 3 years

Every 21-28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months within 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Adagrasib
• Anti-PD-L1 Monoclonal Antibody
• Biopsy Procedure
• Biospecimen Collection
• Computed Tomography
• Durvalumab
• Magnetic Resonance Imaging
• Positron Emission Tomography
• Tremelimumab

Trial Overview

The IMMUNO-BIOMAP trial is testing how well biomarkers predict responses to initial immunotherapies like PD1 or PD-L1 inhibitors, and it's determining the effectiveness of second-line treatments such as tremelimumab, durvalumab, adagrasib, and bevacizumab in patients whose cancer has progressed.

How Is the Trial Designed?

Group I: Arm B (adagrasib, bevacizumab) Experimental Treatment 6 Interventions

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.

Group II: Arm A (tremelimumab, durvalumab) Experimental Treatment 6 Interventions

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.

Group III: Arm 4 (PD[L]1) Experimental Treatment 8 Interventions

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.

Group IV: Arm 3 (close surveillance) Experimental Treatment 9 Interventions

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.

Group V: Arm 2 (continue PD[L]1) Experimental Treatment 8 Interventions

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.

Group VI: Arm 1 (stop treatment, monitoring) Experimental Treatment 9 Interventions

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.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

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ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20648

Clinical outcomes and safety profile of adagrasib in KRAS ...

Results: Six studies involving 400 patients were included in our analysis. Adagrasib showed a median overall survival (OS) of 14.74 months (95% ...

2.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(25)01149-3/fulltext?rss=yes

Adagrasib for KRAS G12C mutated advanced non-small- ...

The primary outcome was progression-free survival, which improved from a median of 3·8 months for patients receiving docetaxel to 5·5 months for ...

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa2204619

Adagrasib in Non–Small-Cell Lung Cancer Harboring a ...

Treatment with adagrasib led to a confirmed objective response rate of 42.9%, a median duration of response of 8.5 months, a median progression- ...

4.

lungcancerstoday.com

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KRYSTAL-7 Data on Adagrasib Plus Pembrolizumab ...

First-line adagrasib and pembrolizumab continue to demonstrate promising efficacy in patients with KRAS G12C mutated non–small cell lung cancer and PD-L1 more ...

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pmc.ncbi.nlm.nih.gov/articles/PMC12554495/

Adagrasib in the treatment of KRASG12C-mutated non- ...

In the phase II KRYSTAL-1 clinical trial, adagrasib demonstrated clinical efficacy in patients with previously treated KRASG12C-mutated non-small cell lung ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11626957/

Adagrasib in the Treatment of KRAS p.G12C Positive ...

Within the NSCLC subgroup, a confirmed anti-tumor response was observed in 53.4% of patients, the median DOR was 14.0 months, and the median PFS ...

7.

dailynews.ascopubs.org

dailynews.ascopubs.org/do/adagrasib-pembrolizumab-shows-promising-efficacy-safety-untreated-advanced-kras-g12c-

Mutated NSCLC in Phase 2 KRYSTAL-7 Trial

The addition of adagrasib to pembrolizumab offers promising efficacy and tolerability in the first-line setting among patients with KRAS G12C-mutated NSCLC.

8.

esmoiotech.org

esmoiotech.org/article/S2590-0188(22)00291-X/fulltext

LBA4 Preliminary safety and efficacy of adagrasib with ...

The combination of adagrasib (ada), a KRAS G12C inhibitor, with an immune checkpoint inhibitor (CPI) has demonstrated enhanced preclinical anti-tumor activity.

9.

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Adagrasib Improves Survival, Responses in KRAS G12C+ ...

Adagrasib improved median PFS to 5.5 months versus 3.8 months with docetaxel, reducing disease progression risk by 42%. · ORR was 32% with ...