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Durvalumab and Tremelimumab for the Treatment of Stage II-IIIB Non-small Cell Lung Cancer

Trial Status: Active

This clinical trial studies the effect of durvalumab and tremelimumab in treating patients with stage II-IIIB non-small cell lung cancer who have undergone surgical removal and completed after surgery treatment with or without radiation therapy and now have detectable tumor DNA in the blood. Durvalumab and tremelimumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving durvalumab and tremelimumab may help prevent cancer from returning (called cancer recurrence) when tumor DNA is detected in the blood.

Inclusion Criteria

  • Age >= 18 years
  • Patients must have pathologically confirmed NSCLC; no mixed NSCLC/small cell lung cancer (SCLC) histology allowed
  • Stage II-IIIB (8th edition) disease who have undergone surgical resection, excluding patients with N3 disease
  • Must have documentation that the tumor does not harbor an activating EGFR mutation, ALK gene rearrangement, or a ROS1 gene rearragement
  • Must have adequately recovered from the toxicity and/or complications of surgery prior to initiation of durvalumab+tremelimumab
  • Detectable ctDNA at a mutant allele frequency of > 0.1% after surgical resection and completion of adjuvant treatment
  • No evidence of clinical disease on computed tomography (CT) chest/abdomen/pelvis at the time of ctDNA detection
  • Completed standard of care adjuvant treatment at least two weeks prior to day 1 of durvalumab+tremelimumab
  • Archived tumor tissue: formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin block or at least 10 unstained slides, with an associated pathology report
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g. Health Insurance Portability and Accountability Act) must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) * Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Body weight > 30 kg
  • Must have a life expectancy of at least 12 weeks
  • Ability to comply with the study protocol, in the investigator’s judgment
  • Neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0g/dl
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (Patients with Gilbert’s disease: =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • International normalized ratio (IN) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (Unless on anticoagulation)
  • Creatinine clearance measured > 40 mL/min or calculated as > 40 mL/min

Exclusion Criteria

  • Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
  • Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non–cancer-related conditions (e.g., hormone replacement therapy) or herbal therapy is acceptable
  • History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of immune therapy and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease; malignancy undergoing active surveillance per stand of care management (e.g., chronic lymphocytic leukemia Rai stage 0, prostate cancer with Gleason score =< 6, and prostate-specific antigen [PSA] =< 10 mg/mL, etc.)
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0 grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician
  • Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on the baseline brain imaging (Response Evaluation Criteria in Solid Tumors [RECIST]) for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or tremelimumab
  • Patients with active hepatitis B or C infections or a history of human immunodeficiency virus (HIV) infection. These participants will be ineligible due to potential for worsening of infection with the use of immunotherapy. Patients with a past or resolved hepatitis B (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B surface antigen [HBsAg]) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
  • History of active primary immunodeficiency
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia; hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; any chronic skin condition that does not require systemic therapy; patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician; celiac disease controlled by diet alone
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, including tuberculosis (TB), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
  • Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure, excluding lung cancer resection, during the course of the study
  • Administration of a live, attenuated vaccine within 30 days before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study. Patients, if enrolled, should not receive live vaccine whilst receiving treatment and up to 30 days after durvalumab, tremelimumab administration
  • History of interstitial lung disease or pneumonitis of any cause
  • Pregnant women are excluded from this study because durvalumab and tremelimumab are investigational agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab and tremelimumab, breastfeeding should be discontinued if the mother is treated with durvalumab and tremelimumab
  • IMMUNOTHERAPY-RELATED EXCLUSION CRITERIA
  • Prior treatment with anti-PD-1, anti-CTLA-4, including tremelimumab or anti-PDL1including durvalumab therapeutic antibody or pathway-targeting agents
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to cycle 1, day 1. The following are exceptions to this criterion: intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection); systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Catherine Ann Shu
Phone: 212-305-3997

PRIMARY OBJECTIVE:

I. To assess the feasibility of identifying and recruiting patients for adjuvant treatment with durvalumab+tremelimumab (D+T) in the setting of molecular residual disease based on circulating tumor deoxyribonucleic acid (ctDNA) positivity after surgical resection and standard of care treatment for stage II-IIIB non small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To assess the dynamics of ctDNA in response to treatment with adjuvant D+T.

II. To determine the duration of disease free survival and overall survival with adjuvant D+T.

III. To evaluate the safety of adjuvant D+T.

OUTLINE:

Patients receive durvalumab intravenously (IV) over 1 hour and tremelimumab IV over 1 hour on day 1. Treatments repeat every 28 days for durvalumab and every 56 days for tremelimumab for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience infusion-associated symptoms may be treated symptomatically with acetaminophen, ibuprofen, diphenhydramine, and/or cimetidine or another H2 receptor antagonist, as per standard practice. Systemic corticosteroids and TNFalpha inhibitors may be administered at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 4 weeks, then every 4 months for 1 year, and then every 4-6 months for up to 3 years.

Trial Phase Phase O

Trial Type Treatment

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Catherine Ann Shu

  • Primary ID AAAT0800
  • Secondary IDs NCI-2020-11948
  • Clinicaltrials.gov ID NCT04625699