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NCT03689855: RamAtezo-1

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

Completed Phase 2 Results posted Last updated 30 July 2024
What this trial tests

Phase 2 trial testing Ramucirumab in Non-small Cell Lung Cancer in 21 participants. Completed in 22 April 2024.

Timeline
5 June 2019
Primary endpoint
16 July 2021
22 April 2024

Quick facts

Lead sponsorWashington University School of Medicine
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment21
Start date5 June 2019
Primary completion16 July 2021
Estimated completion22 April 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Washington University School of Medicine

Who can join

18 and older, any sex, with Non-small Cell Lung Cancer or Non Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · At 6 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.

GroupValue95% CI
Ramucirumab + Atezolizumab1
Clinical Benefit Rate (CBR) Secondary · At 6 weeks

* CBR is defined as the percentage of patients who have achieved responses (complete or partial) 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 st

GroupValue95% CI
Ramucirumab + Atezolizumab16
Toxicity and Tolerability as Measured by Number of Participants Who Experienced Adverse Events Secondary · Through 30 days after completion of treatment (estimated to be 4 months)

-Measured by NCI-CTCAE version 5.0.

Grade 1-2 anemia
GroupValue95% CI
Ramucirumab + Atezolizumab8
Grade 3-5 atrial fibrillation
GroupValue95% CI
Ramucirumab + Atezolizumab1
Grade 3-5 pericardial effusion
GroupValue95% CI
Ramucirumab + Atezolizumab1
Grade 1-2 ear pain
GroupValue95% CI
Ramucirumab + Atezolizumab1
Grade 1-2 hypothyroidism
GroupValue95% CI
Ramucirumab + Atezolizumab4
Grade 1-2 eye pain
GroupValue95% CI
Ramucirumab + Atezolizumab1
Grade 1-2 abdominal pain
GroupValue95% CI
Ramucirumab + Atezolizumab1
Grade 3-5 ascites
GroupValue95% CI
Ramucirumab + Atezolizumab1
Overall Survival (OS) Secondary · Through 2 years after completion of treatment (median length of follow-up 16.3 months, full range=2.3-45.6 months)
GroupValue95% CI
Ramucirumab + Atezolizumab16.37.1 – 20.9
Progression-free Survival (PFS) Secondary · Through 2 years after completion of treatment (median length of follow-up 16.3 months, full range=2.3-45.6 months)

-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

GroupValue95% CI
Ramucirumab + Atezolizumab1.01.0 – 2.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from start of treatment through 30 days after the last administration of the study treatment. All-cause mortality was collected from start of treatment until completion of follow-up. The median length of treatment was 92 days (full range 49 days-812 days). The median length of follow-up was 16.3 months (full range 2.3 months-45.6 months).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ramucirumab + Atezolizumab
Serious: 10/21 (48%)
Deaths: 15/21

Serious adverse events (17 terms)

ReactionSystemRamucirumab + Atezolizumab
COVID-19Infections and infestations
Atrial fibrillationCardiac disorders
Pericardial effusionCardiac disorders
AscitesGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Portal hypertensionHepatobiliary disorders
Urinary tract infectionInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
HyponatremiaMetabolism and nutrition disorders
HeadacheNervous system disorders
StrokeNervous system disorders
Transient ischemic attacksNervous system disorders
Vocal cord paralysisNervous system disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
HypotensionVascular disorders
Other adverse events (92 terms — click to expand)

ReactionSystemRamucirumab + Atezolizumab
HypertensionVascular disorders
ProteinuriaRenal and urinary disorders
NauseaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
AnorexiaMetabolism and nutrition disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Thyroid stimulating hormone increasedInvestigations
DiarrheaGastrointestinal disorders
Weight lossInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Lymphocyte count decreasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
ChillsGeneral disorders
Alkaline phosphatase increasedInvestigations
Creatinine increasedInvestigations
Platelet count decreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HematuriaRenal and urinary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Edema limbsGeneral disorders
Upper respiratory infectionInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
Serum amylase increasedInvestigations
White blood cell decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Allergic rhinitisRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
Non-cardiac chest painGeneral disorders
PainGeneral disorders
Hemoglobin increasedInvestigations

Most-reported serious reactions: COVID-19, Atrial fibrillation, Pericardial effusion, Ascites, Non-cardiac chest pain, Portal hypertension, Urinary tract infection, Infusion related reaction.

Data from ClinicalTrials.gov NCT03689855 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.
    Naimi A, Mohammed RN, Raji A, Chupradit S, et al · · 2022 · cited 350× · PMID 35392976 · DOI 10.1186/s12964-022-00854-y
  2. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  3. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
    Vafaei S, Zekiy AO, Khanamir RA, Zaman BA, et al · · 2022 · cited 190× · PMID 34980128 · DOI 10.1186/s12935-021-02407-8
  4. VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment.
    Zhao Y, Guo S, Deng J, Shen J, et al · · 2022 · cited 166× · PMID 35813484 · DOI 10.7150/ijbs.70958
  5. The Combination of Immune Checkpoint Blockade and Angiogenesis Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer.
    Ren S, Xiong X, You H, Shen J, et al · · 2021 · cited 78× · PMID 34149730 · DOI 10.3389/fimmu.2021.689132
  6. Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness.
    Barnestein R, Galland L, Kalfeist L, Ghiringhelli F, et al · · 2022 · cited 66× · PMID 36117524 · DOI 10.1080/2162402x.2022.2120676
  7. Immunotherapy resistance in non-small-cell lung cancer: From mechanism to clinical strategies.
    Zhou S, Yang H. · · 2023 · cited 64× · PMID 37090727 · DOI 10.3389/fimmu.2023.1129465
  8. Prospect of immunotherapy combined with anti-angiogenic agents in patients with advanced non-small cell lung cancer.
    Liang H, Wang M. · · 2019 · cited 43× · PMID 31616186 · DOI 10.2147/cmar.s212238

Verify or expand the search:

Other trials of Ramucirumab

Trials testing the same drug.

Other recruiting trials for Non-small Cell Lung Cancer

Currently open trials in the same condition.

Other Washington University School of Medicine trials

Trials by the same sponsor.

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