Ramucirumab and Atezolizumab After Progression on Any Immune Checkpoint Blocker in NSCLC

NCT03689855 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201810163
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer; Non Small Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  * 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.

  At 6 weeks

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  At 6 weeks

• Toxicity and Tolerability as Measured by Number of Participants Who Experienced Adverse Events

  Through 30 days after completion of treatment (estimated to be 4 months)

• Overall Survival (OS)

  Through 2 years after completion of treatment (median length of follow-up 16.3 months, full range=2.3-45.6 months)

• Progression-free Survival (PFS)

  Through 2 years after completion of treatment (median length of follow-up 16.3 months, full range=2.3-45.6 months)

Study Arms (1)

Ramucirumab + Atezolizumab

EXPERIMENTAL

* 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; Drug: Atezolizumab; Procedure: Peripheral blood draw; Procedure: Biopsy

Interventions

Ramucirumab DRUG

Ramucirumab is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient.

Also known as: Cyramza

Ramucirumab + Atezolizumab

Atezolizumab DRUG

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).

Also known as: Tecentriq

Ramucirumab + Atezolizumab

Peripheral blood draw PROCEDURE

-Baseline and Cycle 2 Day 1

Ramucirumab + Atezolizumab

Biopsy PROCEDURE

* 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.

Ramucirumab + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Xing P, Wang M, Zhao J, Zhong W, Chi Y, Xu Z, Li J. Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy. Thorac Cancer. 2021 Oct;12(20):2825-2828. doi: 10.1111/1759-7714.14113. Epub 2021 Aug 18.

  PMID: 34409776 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ramucirumab; atezolizumab; Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Daniel Morgensztern, M.D.
• Organization: Washington University School of Medicine

danielmorgensztern@wustl.edu

314-747-7948

Study Officials

• Daniel Morgensztern, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2018
• First Posted: October 1, 2018
• Study Start: June 5, 2019
• Primary Completion: July 16, 2021
• Study Completion: April 22, 2024
• Last Updated: July 30, 2024
• Results First Posted: August 11, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)