Clinical Trials /

Pembrolizumab in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer

NCT02955758

Description:

This phase II trial studies how well pembrolizumab works in treating patients with non-squamous non-small cell lung cancer which has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Patients With Metastatic Non-squamous Non-small Cell Lung Cancer
  • Official Title: A Phase 2 Trial of Pembrolizumab in Metastatic Non-squamous NSCLC Examining Circulating Tumor DNA Levels as a Surrogate Biomarker of Response

Clinical Trial IDs

  • ORG STUDY ID: IRB-37785
  • SECONDARY ID: NCI-2016-01311
  • SECONDARY ID: IRB-37785
  • SECONDARY ID: LUN0085
  • NCT ID: NCT02955758

Conditions

  • Metastatic Non-Squamous Non-Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

This phase II trial studies how well pembrolizumab works in treating patients with non-squamous non-small cell lung cancer which has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To correlate circulating tumor DNA (ctDNA) levels measured using cancer personalized
      profiling by deep sequencing (CAPP-Seq) with radiographic tumor assessments using Response
      Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria in patients with
      metastatic non-squamous non-small cell lung cancer (NSCLC) treated with pembrolizumab.

      SECONDARY OBJECTIVES:

      I. To correlate PD-L1 assessment on pre-treatment tumor samples with objective response using
      RECIST v1.1 criteria in patients with metastatic non-squamous NSCLC treated with
      pembrolizumab.

      II. To determine the overall response rate (ORR) using RECIST v1.1 criteria in patients with
      metastatic non-squamous NSCLC treated with pembrolizumab.

      III. To determine the progression-free survival (PFS) using RECIST v1.1 in patients with
      metastatic non-squamous NSCLC treated with pembrolizumab.

      IV. To determine the overall survival (OS) in patients with metastatic non-squamous NSCLC
      treated with pembrolizumab.

      V. To determine the safety and tolerability of pembrolizumab in patients with metastatic
      non-squamous NSCLC.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Has a pathologically proven recurrent or metastatic non squamous non small cell lung
             cancer

          2. (a) Previously received at least one line of prior systemic therapy for metastatic
             disease.

             i. If the patient has a sensitizing EGFR mutation or ALK rearrangement, the patient
             must have received at least one prior targeted therapy for metastatic disease (ie,
             EGFR TKI therapy or ALK TKI therapy, respectively).

             ii. There is no limit on prior therapies allowed. Patients must have completed
             previous treatment (including other investigational therapy) in greater than or equal
             to the following times prior to initiation of trial treatment:

               1. Anti cancer monoclonal antibody (mAb) therapy must be completed ≥ 3 weeks prior
                  to trial treatment

               2. Chemotherapy administered in a daily or weekly schedule must be completed ≥ 1
                  week prior to trial treatment

               3. Chemotherapy administered in an every 2 week schedule must be completed ≥ 2 weeks
                  prior to trial treatment

               4. Chemotherapy administered in an every 3 week schedule must be completed ≥ 3 weeks
                  prior to trial treatment

               5. Targeted small molecule therapy must be completed ≥ 1 week prior to trial
                  treatment OR (b) Have not received prior systemic therapy for their cancer in
                  recurrent or metastatic setting, AND have a tumor with Tumor Proportion Score
                  (TPS) ≥ 50% as measured by 22C3 PD L1 IHC test, AND no evidence of a sensitizing
                  EGFR mutation or ALK rearrangement.

          3. Prior radiation therapy allowed as long as completed in the following times prior to
             initiation of trial treatment:

               1. Definitive curative intent radiation ≥ 3 weeks prior to trial treatment

               2. Palliative body radiation ≥ 1 week prior to trial treatment

               3. Stereotactic brain radiation ≥ 1 week prior to trial treatment

               4. Whole brain radiation ≥ 2 weeks prior to trial treatment

          4. Patients with previously treated (with radiation or surgery) brain metastases that are
             stable are allowed. Patients with stable or progressing metastases must have
             metastases ≤ 1.5 cm, be asymptomatic, and either not be on steroids or be on 10 mg
             prednisone equivalent or less.

          5. Has measurable disease based on RECIST v1.1 criteria

          6. Is medically able and willing to undergo needle biopsy of a tumor lesion. PD L1
             expression is not required to enroll in the trial.

          7. Has life expectancy ≥ 3 months

          8. Ability to understand and the willingness to sign a written informed consent document.

          9. ≥ 18 years of age on day of signing informed consent

         10. ECOG performance status of 0 or 1 (Appendix A)

         11. Adequate organ function:

               1. Absolute neutrophil count (ANC) ≥ 1,000/mcL

               2. Platelets ≥ 75,000/mcL

               3. Hemoglobin ≥ 8 g/dL

               4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated
                  creatinine clearance ≥ 50 mL/min for patient with creatinine levels > 1.5 x
                  institutional ULN

               5. Serum total bilirubin ≤ 1.5 x ULN OR Direct bilirubin ≤ ULN for patients with
                  total bilirubin levels > 1.5 ULN

               6. AST (SGOT) and ALT (SGPT) ≤ 3 x ULN OR ≤ 5 x ULN for patients with liver
                  metastases

         12. Female patients of childbearing potential must have a negative urine or serum
             pregnancy test prior to the first dose of trial treatment. They must also agree to two
             barrier methods or a barrier method plus a hormonal method, or agree to abstain from
             heterosexual activity, for the course of the study through 120 days after the last
             dose of trial treatment. Females who have been surgically sterilized or are free from
             menses for > 1 year (postmenopausal) may enroll.

         13. Male patients with a female partner of childbearing potential should agree to use a
             barrier method of contraception, or agree to abstain from heterosexual activity for
             the course of the study through 120 days after the last dose of trial treatment.

        Exclusion Criteria:

          1. Is currently receiving another investigational therapy

          2. Has received prior anti PD 1 or anti PD L1 therapy

          3. Has clinically significant toxicities from previous anti cancer therapy that have not
             resolved, or have not stabilized at a new baseline

          4. Has undergone a surgical procedure involving general anesthesia within 2 weeks of
             starting trial treatment, or has inadequate healing or recovery from complications of
             surgery prior to starting trial treatment. This does not apply to low risk procedures
             such as thoracentesis; paracentesis; chest tube/PleurX catheter placement; line
             placement; needle biopsy of tumor; and bronchoscopy.

          5. Is receiving high dose systemic steroid therapy within 3 days of trial treatment.
             Topical and intraarticular steroid injections are allowed, as are physiologic doses of
             systemic steroids (≤ 10 mg of prednisone equivalent daily).

          6. Has carcinomatous meningitis as determined by positive CSF cytology

          7. Has known active additional malignancy that is undergoing active treatment.

          8. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (ie, with use of disease modifying agents, supra physiologic doses of systemic
             corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine,
             insulin; or physiologic corticosteroid replacement therapy for adrenal or pituitary
             insufficiency, etc.) is not considered a form of systemic treatment. Asthma; type I
             diabetes mellitus; hypothyroidism; and vitiligo are allowed.

          9. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the patient's
             participation for the full duration of the trial, or is not in the best interest of
             the patient to participate, in the opinion of the treating investigator. This includes
             known active tuberculosis; Grade 3 active infection; history of allogeneic bone marrow
             transplant or solid organ transplant; known history of Human Immunodeficiency Virus
             (HIV); known active Hepatitis B (eg, Hep B DNA positive in prior 3 months) or known
             active Hepatitis C (eg, HCV RNA [qualitative] is detected in prior 3 months).

         10. Known active interstitial lung disease, or current (non infectious) pneumonitis or
             history of (non infectious) pneumonitis that required oral steroids.

         11. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:ctDNA levels measured using CAPP-Seq
Time Frame:Up to 2 years
Safety Issue:
Description:Circulating tumor DNA (ctDNA) levels will be measured using Cancer personalized profiling by deep sequencing (CAPP Seq) with radiographic tumor assessments using RECIST v1.1 criteria in patients with metastatic NSCLC treated with pembrolizumab. ctDNA will be measured as percentage of total circulating free DNA.

Secondary Outcome Measures

Measure:Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 4.03
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Overal Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Overal Response Rate (ORR) defined as proportion of complete responses + partial responses will be measured using RECIST v1.1 criteria
Measure:Overall Survival (OS)
Time Frame:From the time of first treatment with pembrolizumab to the time of death, assessed up to 2 years
Safety Issue:
Description:
Measure:PFS measured using RECIST v1.1 criteria
Time Frame:From the time of first treatment with pembrolizumab to the time of progression or death from any cause, whichever comes earlier, assessed up to 2 years
Safety Issue:
Description:Progression-free survival (PFS) will be measured from the time of first treatment with pembrolizumab to the time of radiographic progression, unequivocal clinical progression, or death from any cause, whichever comes earlier

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Joel Neal

Last Updated

March 16, 2021