Ramucirumab, Atezolizumab and N-803 After Progression on Any Immune Checkpoint Blocker in NSCLC

NCT05007769 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 21-x234
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators hypothesize that the addition of ramucirumab and N-803 will augment the clinical activity of atezolizumab, and in order to evaluate the exact mechanism of action of the combination, the investigators propose a comprehensive analysis of paired peripheral blood samples collected during this study.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  * ORR is defined as the proportion of participants achieving complete response or partial response measured according to RECIST 1.1 * 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. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Through completion of treatment (estimated to be 6 months)

Secondary Outcomes (7)

• Number of study treatment related adverse events as measured by NCI-CTCAE version 5.0

  From start of treatment through 30 days after completion of treatment (estimated to be 7 months)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 30 months)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 30 months)

• Immune best overall response (iBOR)

  Through completion of treatment (estimated to be 6 months)

• Immune progression-free survival (iPFS)

  Through completion of follow-up (estimated to be 30 months)

Study Arms (1)

Ramucirumab + Atezolizumab + N-803

EXPERIMENTAL

-Ramucirumab intravenously (IV) on Day 1, atezolizumab IV on Day 1, and N-803 subcutaneous (SC) on Day 1 of each cycle. Cycles are 21 days.

Drug: Ramucirumab; Drug: Atezolizumab; Drug: N-803

Interventions

Ramucirumab DRUG

Will be supplied by Lilly Oncology, free of charge to the participant

Also known as: Cyramza

Ramucirumab + Atezolizumab + N-803

Atezolizumab DRUG

Atezolizumab will be commercially available.

Also known as: Tecentriq

Ramucirumab + Atezolizumab + N-803

N-803 DRUG

Will be supplied free of charge to the participants by ImmunityBio

Ramucirumab + Atezolizumab + N-803

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 mutations, ALK or ROS1 rearrangements are not eligible.
• 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. Results of the 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. There is no limit on the number of lines of prior therapy a patient may have received.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcl
• Platelets ≥ 100,000/mcl
• 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 such as 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 fludrocortisone for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. Patients using up to 10 mg of prednisone or equivalent per day are eligible.
• 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 standard of care management including Rai Stage 0 chronic lymphocytic leukemia, prostate cancer with Gleason score ≤ 6 and prostate-specific antigen (PSA) ≤ 10 ng/mL.
• Having received any other investigational agents within 30 days or five times the half-life of the agent (whichever is sooner) of the planned start of the protocol therapy. Patients may be screened and consented but may not begin therapy within that 30 day washout period.
• 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 starting therapy.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab, ramucirumab, N-803, any other immune checkpoint blockade, chimeric or humanized antibodies, fusion proteins, or other agents used in the study.
• A history of prior severe immune-related adverse events requiring permanent discontinuation of the checkpoint inhibitors including all grade 4 toxicities and selected grade 3 toxicities such as pneumonitis, pancreatitis, neurological, cardiovascular, ocular, or renal adverse events.
• The patient is receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325mg/day) is permitted.
• The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy. Patients with unresected primary tumors or local recurrence who develop Grade 3 and 4 venous thromboembolism during the study may also receive anticoagulation and continue ramucirumab therapy provided that the tumor does not confer an excessive bleeding risk, in the opinion of the patient's physician.
• Uncontrolled or poorly controlled hypertension with blood pressure \> 160 mmHg systolic or \> 100 mmHg diastolic for \> 4 weeks despite standard medical management.
• The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
• The patient has experienced any Grade 3 or 4 gastrointestinal bleeding within 3 months prior to first dose of protocol therapy.
• 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.
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia, 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
• ImmunityBio, Inc.: collaborator

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; ALT-803

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

Study Officials

• Daniel Morgensztern, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

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: August 9, 2021
• First Posted: August 16, 2021
• Study Start: October 31, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2026
• Last Updated: November 5, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share