Clinical Trials /

Study of Durvalumab + Tremelimumab in NSCLC Patients After Adjuvant Treatment

NCT04625699

Description:

The purpose of this study is to determine whether it is feasible and safe to give research participants investigational treatment with durvalumab and tremelimumab after they have completed standard treatment for NSCLC and once they have detectable circulating tumor DNA (ctDNA) in the blood before there is evidence of disease recurrence on imaging studies. These investigational agents are a type of immunotherapy, which is a treatment that activates your own body's immune system to treat cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Durvalumab + Tremelimumab in NSCLC Patients After Adjuvant Treatment
  • Official Title: A Feasibility Study of Durvalumab + Tremelimumab in Resected Non Small Cell Lung Cancer (NSCLC) Patients With Detectable Circulating Tumor DNA After Adjuvant Treatment

Clinical Trial IDs

  • ORG STUDY ID: AAAT0800
  • NCT ID: NCT04625699

Conditions

  • Nonsmall Cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736, IMFINZIdurvalumab+ tremelimumab
Tremelimumabformerly CP-675,206durvalumab+ tremelimumab

Purpose

The purpose of this study is to determine whether it is feasible and safe to give research participants investigational treatment with durvalumab and tremelimumab after they have completed standard treatment for NSCLC and once they have detectable circulating tumor DNA (ctDNA) in the blood before there is evidence of disease recurrence on imaging studies. These investigational agents are a type of immunotherapy, which is a treatment that activates your own body's immune system to treat cancer.

Detailed Description

      This is an open label, single arm, pilot study of adjuvant durvalumab+ tremelimumab (D+T) for
      patients with stage II-IIIB (excluding N3) NSCLC.The trial will evaluate the feasibility of
      adjuvant D+T in patients who have undergone surgical resection and standard of care (SOC)
      adjuvant treatment and subsequently develop detectable plasma ctDNA. 15 evaluable patients
      will be enrolled. Patients with resected stage II-IIIB (excluding N3) NSCLC who have
      completed adjuvant standard of care treatment will be pre-screened and consented for the
      trial. They will undergo ctDNA testing with the Signatera assay at the completion of adjuvant
      treatment and every 4 months thereafter with standard CT imaging assessment up to 1 year.
      Patients with detectable ctDNA at a mutant allele frequency of >0.1% and no evidence of
      recurrence on CT imaging will be enrolled in the trial. They will receive durvalumab every 4
      weeks for 4 cycles and tremelimuamb on cycles 1 and 3 with concomitant plasma ctDNA
      quantification. Patients will be followed with standard CT imaging of the chest as well as
      routine and exploratory blood tests every 4 months until 1 year after completion of D+T. They
      will also be followed for up to 3 years for determination of DFS and OS.
    

Trial Arms

NameTypeDescriptionInterventions
durvalumab+ tremelimumabExperimentaldurvalumab will be administered Q4weeks and tremelimumab will be administered Q8 weeks
  • Durvalumab
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age greater than or equal to 18 years

          -  Patients must have pathologically confirmed NSCLC; no mixed NSCLC/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 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
             agespecific 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 folliclestimulating 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

          -  Adequate organ and marrow function

        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 NCI CTCAE 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 (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

          -  Patients with active hepatitis B or C infections or a history of 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 HBV infection (defined as the
             presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
             Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
             reaction is negative for HCV 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 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of evaluable patients enrolled
Time Frame:36 months
Safety Issue:
Description: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 ctDNA positivity after surgical resection and standard of care treatment for stage II-IIIB NSCLC. The target is a total of 15 with a projected accrual rate of 2-3 patients per month.

Secondary Outcome Measures

Measure:ctDNA clearance
Time Frame:36 months
Safety Issue:
Description:To assess the dynamics of ctDNA in response to treatment with adjuvant durvalumab+tremelimumab. This will be reported with 95% confidence intervals based on the exact binomial distribution.
Measure:Overall survival
Time Frame:Up to 36 months
Safety Issue:
Description:To determine the duration of overall survival with adjuvant durvalumab+tremelimumab
Measure:Disease free survival
Time Frame:Up to 36 months
Safety Issue:
Description:To determine the duration of disease free survival with adjuvant durvalumab+tremelimumab
Measure:Adverse events rate
Time Frame:36 months
Safety Issue:
Description:To evaluate the safety of adjuvant D+T, adverse events will be scored according to NCI CTCAE v5.0 and their frequency and nature will be tabulated by categories. This will be reported with 95% confidence intervals based on the exact binomial distribution.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Catherine Shu

Trial Keywords

  • II-IIIB

Last Updated

November 6, 2020