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NCT03738228

Atezolizumab Before and/or With Chemoradiotherapy in Immune System Activation in Patients With Node Positive Stage IB2, II, IIIB, or IVA Cervical Cancer

Completed Phase 1 Results posted Last updated 12 November 2025
What this trial tests

Phase 1 trial testing Atezolizumab in Cervical Adenocarcinoma in 40 participants. Completed in 12 September 2025.

Timeline
7 January 2019
Primary endpoint
1 May 2022
12 September 2025

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment40
Start date7 January 2019
Primary completion1 May 2022
Estimated completion12 September 2025
Sites16 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, female only, with Cervical Adenocarcinoma or Cervical Adenosquamous Carcinoma. 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.

Immune Response Primary · Arm A: 42 days from the first dose of Atezolizumab Arm B: 21 days from the first dose of Atezolizumab

The immune response is measured by total T cell receptor beta (TCRB) clonal expansion in peripheral blood at day 21 from baseline using Adaptive Biotechnologies' immunoSEQ platform from Day -21 to Day 21 for group 1 (i.e., Arm A), and from Day 0 to Day 21 for group 2 (i.e., Arm B). The higher number of total TCR clonal expansion indicates better immune response.

GroupValue95% CI
Arm A132.7± 175.7
Arm B192.8± 174.4
Percentage of Participants With Dose Limiting Toxicities Secondary · Arm A: 111 days, i.e., from start of the priming dose of atezolizumab until 30 days after the completion of CRT Arm B: 90 days, i.e., from start of CRT until 30 days after the completion of CRT(Chemoradiation therapy).

A DLT is defined as any drug related adverse effects that occur during treatment period until 30 days after the completion of CRT and meet the criteria as evaluated by NCI CTCAE v.5 unless clearly unrelated to study therapy (e.g., disease progression).

GroupValue95% CI
Arm A00 – 17.07
Arm B21.436.11 – 46.57
Post-treatment 3-month PET/CT Metabolic Response Secondary · 3 months after completion of study treatment

Percentage of participants with complete post-treatment 3-month PET/CT metabolic response. The post-treatment 3-month PET/CT metabolic response is evaluated based on the ratio of post-treatment week-12 PET-CT SUVmax to base-line PET-CT scan SUV max, and the response will be classified as complete metabolic response for the ratio \< 0.34, or classified as partial metabolic response for 0.34 \<= the ratio \< 0.76, or classified as stable metabolic response for 0.76 \<= the ratio \< 1.25, or classified as progressive metabolic disease for the ratio \>= 1.25.

GroupValue95% CI
Arm A71.434.1 – 94.7
Arm B5024.5 – 75.5
Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)5 Secondary · Arm A: 111 days, i.e., from start of the priming dose of atezolizumab until 30 days after the completion of CRT Arm B 90 days, i.e., from start of CRT until 30 days after the completion of CRT

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v5.0.

Blood and lymphatic system disorders
GroupValue95% CI
Arm A4
Arm B6
Cardiac Disorders
GroupValue95% CI
Arm A1
Arm B0
Gastrointestinal Disorders
GroupValue95% CI
Arm A2
Arm B4
General disorders and administrative site conditions
GroupValue95% CI
Arm A1
Arm B0
Infections and Infestations
GroupValue95% CI
Arm A3
Arm B2
Investigations
GroupValue95% CI
Arm A2
Arm B7
Metabolism and Nutrition Disorders
GroupValue95% CI
Arm A0
Arm B4
Musculoskeletal and Connective Tissue Disorders
GroupValue95% CI
Arm A0
Arm B2
T Cell Receptor (TCR) Simpson Clonality Secondary · Arm A: 42 days from the first dose of Atezolizumab Arm B: 21 days from the first dose of Atezolizumab

TCR Simpson clonality in peripheral blood is measured at day 21 using Adaptive Biotechnologies' immunoSEQ platform. It quantitates the extent of mono- or oligoclonal dominance within a TCR repertoire by measuring the shape of the clone frequency distribution ranging from 0 to 1, where values approaching 1 indicate a nearly monoclonal population.

GroupValue95% CI
Arm A0.05050.0102 – 0.2305
Arm B0.04480.0112 – 0.1355
Pre-treatment PD-L1 Expression Secondary · Within 3 days after randomization but before start of study treatment

Pre-treatment PD-L1 SP142 positive immune cells in tumor area in formalin-fixed paraffin-embedded (FFPE) biopsy primary tumor tissues

GroupValue95% CI
Arm A0.750 – 8
Arm B0.50 – 3
Disease-free Survival (DFS) at 2 Years Secondary · Up to 2 years

Percentage of participants who survive disease-free at 2 years, where DFS is defined as the duration of time from study entry to date of first documented recurrence or progression of disease or death, whichever occurs first. Progression is assessed by RECIST 1.1.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
Arm A68.447 – 85.3
Arm B52.931.1 – 74
T Cell Receptor (TCR) Diversity Secondary · Arm A: 42 days from the first dose of Atezolizumab Arm B: 21 days from the first dose of Atezolizumab

TCR diversity in peripheral blood is measured at day 21 by counting the number of unique rearrangements to a common number of T cells using Adaptive Biotechnologies' immunoSEQ platform. A higher TCR diversity indicates a richer TCR repertoire.

GroupValue95% CI
Arm A121184448 – 14740
Arm B122378366 – 14906

Adverse events — posted to ClinicalTrials.gov

Time frame: Arm A: 111 days, i.e., from start of the priming dose of atezolizumab until 30 days after the completion of CRT Arm B: 90 days, i.e., from start of CRT until 30 days after the completion of CRT. All-Cause Mortality monitored/assessed up to 2 years.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A
Serious: 6/19 (32%)
Deaths: 4/19
Arm B
Serious: 7/17 (41%)
Deaths: 2/17

Serious adverse events (13 terms)

ReactionSystemArm AArm B
DiarrheaGastrointestinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
Myocardial InfarctionCardiac disorders
Small Intestinal ObstructionGastrointestinal disorders
NauseaGastrointestinal disorders
Flu Like SymptomsGeneral disorders
FeverGeneral disorders
Urinary Tract InfectionInfections and infestations
HypokalemiaMetabolism and nutrition disorders
Musculoskeletal And Connective Tissue Disorder - OMusculoskeletal and connective tissue disorders
Vaginal HemorrhageReproductive system and breast disorders
Pelvic PainReproductive system and breast disorders
Other adverse events (102 terms — click to expand)

ReactionSystemArm AArm B
NauseaGastrointestinal disorders
DiarrheaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
Platelet Count DecreasedInvestigations
HypokalemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
Neutrophil Count DecreasedInvestigations
White Blood Cell DecreasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
TinnitusEar and labyrinth disorders
Abdominal PainGastrointestinal disorders
PainGeneral disorders
Urinary Tract InfectionInfections and infestations
AnorexiaMetabolism and nutrition disorders
DizzinessNervous system disorders
Vaginal HemorrhageReproductive system and breast disorders
Hot FlashesVascular disorders
FeverGeneral disorders
Creatinine IncreasedInvestigations
Aspartate Aminotransferase IncreasedInvestigations
Alanine Aminotransferase IncreasedInvestigations
HeadacheNervous system disorders
DysuriaRenal and urinary disorders
FloatersEye disorders
Lymphocyte Count DecreasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
Neck PainMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
AgitationPsychiatric disorders
Urinary UrgencyRenal and urinary disorders
Vaginal DischargeReproductive system and breast disorders
Pelvic PainReproductive system and breast disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
BloatingGastrointestinal disorders
Rectal HemorrhageGastrointestinal disorders
Gastroesophageal Reflux DiseaseGastrointestinal disorders

Most-reported serious reactions: Diarrhea, Febrile Neutropenia, Anemia, Myocardial Infarction, Small Intestinal Obstruction, Nausea, Flu Like Symptoms, Fever.

Data from ClinicalTrials.gov NCT03738228 adverse events section.

Sponsor's own description

This phase I trial studies how well atezolizumab before and/or with standard of care chemoradiotherapy works in immune system activation in patients with stage IB2, II, IIIB, or IVA cervical cancer that has spread to the lymph nodes. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before and/or with chemoradiotherapy may lower the chance of tumors growing or spreading.

Publications & conference data

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

  1. Global challenges of radiotherapy for the treatment of locally advanced cervical cancer.
    Mayadev JS, Ke G, Mahantshetty U, Pereira MD, et al · · 2022 · cited 140× · PMID 35256434 · DOI 10.1136/ijgc-2021-003001
  2. Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer.
    Mayadev JS, Enserro D, Lin YG, Da Silva DM, et al · · 2020 · cited 71× · PMID 31774464 · DOI 10.1001/jamaoncol.2019.3857
  3. Advances in immunotherapy for cervical cancer.
    Wendel Naumann R, Leath CA. · · 2020 · cited 63× · PMID 32740092 · DOI 10.1097/cco.0000000000000663
  4. Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety.
    Williamson CW, Sherer MV, Zamarin D, Sharabi AB, et al · · 2021 · cited 49× · PMID 33620731 · DOI 10.1002/cncr.33424
  5. Kickstarting Immunity in Cold Tumours: Localised Tumour Therapy Combinations With Immune Checkpoint Blockade.
    Appleton E, Hassan J, Chan Wah Hak C, Sivamanoharan N, et al · · 2021 · cited 46× · PMID 34733287 · DOI 10.3389/fimmu.2021.754436
  6. Keynote-158 study, FDA granted accelerated approval of pembrolizumab for the treatment of patients with advanced PD-L1-positive cervical cancer.
    Borcoman E, Le Tourneau C. · · 2020 · cited 34× · PMID 33437810 · DOI 10.21037/atm-20-2656
  7. Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer.
    Mayadev J, Zamarin D, Deng W, Lankes H, et al · · 2020 · cited 34× · PMID 31871115 · DOI 10.1136/ijgc-2019-001012
  8. Immunotherapy for Gynecologic Cancer: Current Applications and Future Directions.
    Lynam S, Lugade AA, Odunsi K. · · 2020 · cited 29× · PMID 31833846 · DOI 10.1097/grf.0000000000000513

Verify or expand the search:

Other trials of Atezolizumab

Trials testing the same drug.

Other recruiting trials for Cervical Adenocarcinoma

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03738228.

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