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Non-small Cell Lung CancerPhase 2RANNCT05007769

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

A Phase 2 study testing Ramucirumab, Atezolizumab and N-803 in people with Non-small Cell Lung Cancer and Non-small Cell Carcinoma, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ramucirumab, Atezolizumab and N-803
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
31 Oct 2021to 30 Apr 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • PTT/aPTT < 1.5 x ULN Note: Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin (LMWH) for a minimum duration of 28 days. 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 such as 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
  • Because the teratogenicity of ramucirumab is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • -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.
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  • 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.
  • Serious or non-healing would, ulcer, or bone fracture within 28 days prior to Cycle 1 Day 1.
  • Cirrhosis grade Child-Pugh B or C or cirrhosis of any degree with history of encephalopathy or clinically meaningful ascites, defined as requiring diuretics or paracentesis.
  • Undergone major surgery within 28 days prior to Cycle 1 Day 1, minor surgery or 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.
  • Active tuberculosis.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with the former 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.
  • 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 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 during the 3 months prior to Cycle 1 Day 1. Venous port or catheter thrombosis or superficial venous thrombosis are not considered significant.
  • Pregnant or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of study entry.
  • Known HIV-positivity.

About this study

Official title: A Phase II, Single-center, Open-label Study of Ramucirumab, Atezolizumab and N-803 After Progression on Any Immune Checkpoint Blocker in NSCLC (RAN)

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.

Being tested
Ramucirumab, Atezolizumab, N-803
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RamucirumabDrug

    Also called Cyramza

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

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be commercially available.

  • N-803Drug

    Will be supplied free of charge to the participants by ImmunityBio

Study groups in NCT05007769
Study groupRoleWhat they receive
Ramucirumab + Atezolizumab + N-803Experimental-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.
Receives: Drug: Ramucirumab; Drug: Atezolizumab; Drug: N-803

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Through completion of treatment (estimated to be 6 months)

Secondary outcomes (7)

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

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

  2. Overall survival (OS)

    -Defined as the duration of time from the start date of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up date.

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

  3. Progression-free survival (PFS)

    • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    • Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

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

  4. Immune best overall response (iBOR)

    • Defined as the best time point response recorded from the start of the study treatment until the end of treatment, taking into account any requirement for confirmation.
    • iBOR will be measured by iRECIST criteria

    Measured: Through completion of treatment (estimated to be 6 months)

  5. Immune progression-free survival (iPFS)

    • Defined by the first date at which progression criteria are met (i.e., the date of immune unconfirmed progression (iUPD) provided that immune confirmed progression (iCPD) is confirmed at the next assessment). If iUPD occurs, but later that patient develops immune stable disease (iSD), immune partial response (iPR), or immune complete response (iCR), then this initial iUPD date is not the date of PD. If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the iUPD date should still be used in the following scenarios: if the patient stops protocol treatment because they were not judged to be clinically stable, or no further response assessments are done (because of patient refusal, protocol noncompliance, or patient death); the next time point response are all iUPD, and iCPD never occurs; or the patient dies from their cancer.
    • Progression will be measured per iRECIST criteria

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

  6. Clinical benefit rate (CBR)

    • Defined as the percentage of participants who have achieved complete response, partial response, or stable disease 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.

    Measured: Through completion of treatment (estimated to be 6 months)

  7. Number of discontinuations due to treatment-related adverse events

    Measured: From start of treatment through completion of treatment (estimated to be 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2021
  2. Study start31 Oct 2021 (estimated)
  3. Primary completion30 Apr 2024 (estimated)
  4. Study completion30 Apr 2026 (estimated)

Why it stopped: Lost funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05007769
Sponsor's protocol ID
21-x234
Acronym
RAN
Status last verified
Oct 2021
First submitted
9 Aug 2021
Last updated
5 Nov 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ramucirumab, Atezolizumab and N-803 in people with Non-small Cell Lung Cancer and Non-small Cell Carcinoma, run by Washington University School of Medicine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: Through completion of treatment (estimated to be 6 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05007769.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.

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