Recruiting
Phase 2

PD1 Immunotherapy

Sponsor:

City of Hope Medical Center

Code:

NCT07288034

Conditions

Lung Non-Small Cell Carcinoma

Stage IIIB Lung Cancer AJCC v8

Stage IV Lung Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Adagrasib

Anti-PD-L1 Monoclonal Antibody

Anti-PD1 Monoclonal Antibody

Bevacizumab

Biopsy Procedure

Study Details

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

Study ID

NCT07288034

Start date

Apr 8, 2026

Status verified date

Apr, 2026

Completion date

Oct 8, 2028

Anticipated

Primary completion date

Oct 8, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
  • Alanine aminotransferase (ALT) ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
  • Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula
  • If seropositive for HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable

  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • 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
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • PART II: Documented informed consent (for Part II) of the participant and/or legally authorized representative.

  • Assent, when appropriate, will be obtained per institutional guidelines
  • PART II: ECOG ≤ 2
  • PART II: Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
  • PART II: ANC ≥ 1,500/mm\^3

  • NOTE: Growth factor is not permitted within 14 days of ANC assessment
  • PART II: Platelets ≥ 100,000/mm\^3

  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
  • PART II: Hemoglobin ≥ 9g/dL

  • NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment
  • PART II: Total bilirubin ≤ 1.5 x ULN
  • PART II: AST ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
  • PART II: ALT ≤ 3.0 x ULN (5 x ULN allowed if liver metastases)
  • PART II: Creatinine clearance of ≥ 50 mL/min per the Cockcroft-Gault formula

Exclusion Criteria:

  • 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
  • PART II: 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 class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication
  • PART II ARM A ONLY: 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
  • PART II ARM B ONLY: Grade ≥ 2 proteinuria as demonstrated by ≥ 2+ protein and ≥ 1.0 g of protein with 24-hour urine collection (patients found to have ≥ 2+ protein on dipstick urinalysis must have 24-hour urine collection and demonstrate < 1g of protein in 24 hours in order to be eligible for treatment)
  • PART II: Clinical evidence of 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
  • PART II: Clinically significant uncontrolled illness
  • PART II: Active infection requiring antibiotics
  • PART II: Other active malignancy
  • PART II FEMALES ONLY: Pregnant or breastfeeding
  • PART II: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Study Design

Enrollment

535 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

Adagrasib

Given PO

Anti-PD-L1 Monoclonal Antibody

Given PD-L1-based immunotherapy

Anti-PD1 Monoclonal Antibody

Given PD1-based immunotherapy

Bevacizumab

Given IV

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood, CSF, ascites and pleural fluid sample collection

Chemotherapy

Given chemotherapy

Computed Tomography

Undergo CT

Durvalumab

Given IV

Magnetic Resonance Imaging

Undergo PET

Monitoring

Undergo monitoring

Positron Emission Tomography

Undergo PET

Surveillance

Undergo close surveillance

Tremelimumab

Given IV

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 ]
  • PFS by arm for second-line treatment (Part II) [ Time Frame: From the start of treatment to disease progression or death from any cause, whichever occurs first, assessed up to 3 years ]

Central Contacts and Locations

Locations

CTCA at Western Regional Medical Center

Recruiting

Goodyear, Arizona, United States, 85338

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Corona

Recruiting

Corona, California, United States, 92882

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Medical Center

Recruiting

Duarte, California, United States, 91010

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Seacliff

Recruiting

Huntington Beach, California, United States, 92648

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Antelope Valley

Recruiting

Lancaster, California, United States, 93534

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope at Long Beach Elm

Recruiting

Long Beach, California, United States, 90813

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope at Newport Beach Fashion Island

Recruiting

Newport Beach, California, United States, 92660

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope South Pasadena

Recruiting

South Pasadena, California, United States, 91030

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope South Bay

Recruiting

Torrance, California, United States, 90503

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Upland

Recruiting

Upland, California, United States, 91786

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope Atlanta Cancer Center

Recruiting

Newnan, Georgia, United States, 30265

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

City of Hope at Chicago

Recruiting

Zion, Illinois, United States, 60099

Contacts

Ravi Salgia

626-218-9200rsalgia@coh.org

Principal Investigator:

Ravi Salgia

More Information

Sponsor

City of Hope Medical Center

Last update posted

Apr 15, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by City of Hope Medical Center on 2026-04-15.