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Ramucirumab and Atezolizumab After Progression on Any Immune Checkpoint Blocker in NSCLC (RamAtezo-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03689855
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : July 16, 2020
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
Data suggests that combining ramucirumab with immunotherapy in non-small cell lung cancer (NSCLC) patients who have previously received immune checkpoint blockers (ICBs) may be more effective than traditional therapy. The investigators propose a pilot study to test the combination of ramucirumab and atezolizumab in patients with advanced-stage NSCLC patients previously treated with ICB.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Non Small Cell Lung Cancer NSCLC Drug: Ramucirumab Drug: Atezolizumab Procedure: Peripheral blood draw Procedure: Biopsy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ramucirumab and Atezolizumab After Progression on Any Immune Checkpoint Blocker in NSCLC (RamAtezo-1)
Actual Study Start Date : June 5, 2019
Estimated Primary Completion Date : August 31, 2021
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ramucirumab + Atezolizumab
  • Ramucirumab will be given intravenously over the course of an hour on an outpatient basis on Day 1 of each 21-day cycle at a dose of 10 mg/kg.
  • Atezolizumab will be given intravenously on an outpatient basis on Day 1 of each 21-day cycle at a dose of 1200 mg.
Drug: Ramucirumab
Ramucirumab is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient.
Other Name: Cyramza

Drug: Atezolizumab
The initial dose will be administered over 60 minutes (+/- 15 minutes). If the first infusion is tolerated without infusion-associated events, the second infusion may be delivered over 30 minutes (+/- 10 minutes).
Other Name: Tecentriq

Procedure: Peripheral blood draw
-Baseline and Cycle 2 Day 1

Procedure: Biopsy
  • If archival biopsy tissue not available, participant will undergo biopsy at baseline
  • When feasible, a repeated tumor biopsy will be obtained between Cycles 2 and 3 after the scheduled CT scan.




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 12 weeks ]
    • ORR - percentage of participants with a complete or partial response
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Through 2 years after completion of treatment (estimated to be 27 months) ]
  2. Progression-free survival (PFS) [ Time Frame: Through 2 years after completion of treatment (estimated to be 27 months) ]
    -PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  3. Clinical benefit rate (CBR) [ Time Frame: 12 weeks ]
    • CBR is defined as the percentage of patients who have achieved responses or stable disease.
    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  4. Toxicity and tolerability as measured by NCI-CTCAE version 5.0 [ Time Frame: Through 30 days after completion of treatment (estimated to be 4 months) ]
    -Toxicity and tolerability will be measured by all immune-related and serious adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed squamous or non-squamous non-small cell lung cancer. Patients with known EGFR or ALK mutations are eligible only if they have received at least one line of targeted therapy for these mutations.
  • Availability of archival biopsy tissue or willingness to undergo a "baseline" biopsy prior to initiation of the trial for biomarker analysis, including PD-L1 by IHC. Note: Results of PD-L1 testing are not required for enrollment.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • Prior use of an immune checkpoint blocker alone or in combination therapy.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/cumm
    • Platelets ≥ 100,000/cumm
    • Hemoglobin ≥ 9.0 g/dL
    • Total bilirubin ≤ 1.5 x ULN
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x ULN or 5.0 x ULN in the setting of liver metastasis
    • Serum creatinine ≤ 1.5 x ULN or CrCl ≥ 40 mL/min. if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed
  • Adequate coagulation function as defined by:

    • INR ≤ 1.5
    • PTT/aPTT < 1.5 x ULN
  • Note: Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
  • Urinary protein ≤ 1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Treatment with cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1.

    *Note: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea or premedication for contrast dye allergy) are eligible. The use of inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.

  • A history of other malignancy ≤ 3 years previous with the exception of patients with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per SOC management (e.g., Rai Stage 0 chronic lymphocytic leukemia, prostate cancer with Gleason score ≤ 6 and prostate-specific antigen (PSA ≤ 10 ng/mL, etc.).
  • Currently receiving any other investigational agents.
  • Symptomatic or untreated asymptomatic brain metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. The patient may have no evidence of Grade ≥1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before randomization).
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab, ramucirumab, any other immune checkpoint blockade, chimeric or humanized antibodies, fusion proteins, or other agents used in the study.
  • Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
  • Arterial or venous thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment.
  • Uncontrolled or poorly controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
  • Gastrointestinal perforation, and/or fistula, or risk factors for perforation within 6 months prior to enrollment.
  • Grade 3 or 4 gastrointestinal bleeding within 3 months prior to enrollment.
  • History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.

    *Note: Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible.

  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan.
  • Hemoptysis (defined as bright red blood or ≥ ½ teaspoon) within 2 months prior to Cycle 1 Day 1 or with radiographic evidence of intratumor cavitation or radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • Serious or non-healing would, ulcer, or bone fracture within 28 days prior to Cycle 1 Day 1.
  • Undergone major surgery within 28 days prior to Cycle 1 Day 1, or minor surgery/subcutaneous venous access device placement within 7 days prior to Cycle 1 Day 1, or has elective or planned major surgery to be performed during the course of the clinical trial.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis at a level of Child-Pug B or worse, cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis (defined as ascites from cirrhosis requiring diuretics or paracentesis), fatty liver, and inherited liver disease.

    --Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as, HBV surface antigen (HBsAg) positive and HBV core antibody (HbcAb) positive with reflex positive HBV DNA. Note: Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and a positive HBcAb test or treated HCV with negative HCV RNA are eligible.

  • Known HIV-positivity.
  • Active tuberculosis.
  • Administration of a live, attenuated influenza vaccine within 4 weeks before Cycle 1 Day 1 or at any time during the study.
  • Severe infections within 2 weeks prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia. Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1 Day 1. Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • History of deep venous thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to Cycle 1 Day 1.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of study entry.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689855


Contacts
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Contact: Daniel Morgensztern, M.D. (314) 747-7948 danielmorgensztern@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Daniel Morgensztern, M.D.    314-747-7948    danielmorgensztern@wustl.edu   
Principal Investigator: Daniel Morgensztern, M.D.         
Sub-Investigator: Brett Herzog, M.D., Ph.D.         
Sub-Investigator: Maria Baggstrom, M.D.         
Sub-Investigator: Siddhartha Devarakonda, M.D.         
Sub-Investigator: Ramaswamy Govindan, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Timothy Rearden, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Anna Roshal, M.D.         
Sub-Investigator: Saiama Waqar, MBBS         
Sub-Investigator: Jeff Ward, M.D., Ph.D.         
Sub-Investigator: Feng Gao, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Eli Lilly and Company
Investigators
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Principal Investigator: Daniel Morgensztern, M.D. Washington University School of Medicine
Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03689855    
Other Study ID Numbers: 201810163
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: July 16, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Atezolizumab
Ramucirumab
Antineoplastic Agents