NCT03191786: IPSOS

A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy

Completed Phase 3 Results posted Last updated 23 October 2024

What this trial tests

Phase 3 trial testing Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody in Non-Small Cell Lung Cancer in 453 participants. Completed in 25 October 2023.

Timeline

11 September 2017

Primary endpoint
30 April 2022

25 October 2023

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	453
Start date	11 September 2017
Primary completion	30 April 2022
Estimated completion	25 October 2023
Sites	91 locations across Italy, Colombia, Kazakhstan, Ireland, Vietnam, Poland, Denmark, Belgium

Drugs / interventions tested

• Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody — full drug profile →
• Vinorelbine (vinorelbine) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →

Conditions studied

• Non-Small Cell Lung Cancer — all drugs for Non-Small Cell Lung Cancer →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with 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 Survival (OS) Primary · From randomization up to death from any cause (up to approximately 55 months)

OS was defined as the time between the date of randomization and the date of death due to any cause. Kaplan-Meier (KM) estimates were used to calculate median.

Group	Value	95% CI
Atezolizumab	10.3	9.4 – 11.9
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	9.2	5.9 – 11.2

OS Rates at the 6, 12, 18, 24-Months Timepoints Secondary · 6, 12, 18 and 24 months

OS was defined as the time between the date of randomization and the date of death due to any cause. OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm using Kaplan Meier methodology. Percentages were rounded off to the nearest decimal point.

6 Months

Group	Value	95% CI
Atezolizumab	64.0	58.6 – 69.5
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	57.5	49.4 – 65.7

12 Months

Group	Value	95% CI
Atezolizumab	43.7	37.9 – 49.4
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	38.6	30.5 – 46.7

18 Months

Group	Value	95% CI
Atezolizumab	31.4	26.0 – 36.8
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	24.0	16.8 – 31.2

24 Months

Group	Value	95% CI
Atezolizumab	24.3	19.3 – 29.4
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	12.4	6.7 – 18.0

Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Secondary · From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

Objective response rate (ORR)=best overall response (BOR) of either complete response (CR)/partial response (PR), as determined by investigator with use of RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 millimeters (mm). PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. A minimum interval of 6 weeks (42 days) was considered for stable disease (SD) to be assigned as BOR, i.e. in case the single response is SD, PR or

Group	Value	95% CI
Atezolizumab	16.9	12.8 – 21.6
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	7.9	4.2 – 13.5

Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 Secondary · From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

PFS was defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first. Progressive disease (PD) was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. KM estimates were used to calculate median.

Group	Value	95% CI
Atezolizumab	4.2	3.7 – 5.5
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	4.0	2.9 – 5.4

Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1 Secondary · Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

DOR was defined as the time from the first tumor assessment that supports the participants' objective response (CR or PR, whichever is first reported) to documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first, among participants who have a best overall response as CR or PR. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target

Group	Value	95% CI
Atezolizumab	14.0	8.1 – 20.3
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	7.8	4.8 – 9.7

Percentage of Participants With At Least One Adverse Event (AE) Secondary · Baseline up to 90 days after last dose of atezolizumab (approximately 62 months)

An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).

Group	Value	95% CI
Atezolizumab	91.7
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	97.3

Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score Secondary · Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)

EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of patient functioning (physical, emotional, role, cognitive, and social), 3 symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). It was scored according to EORTC scoring manual (Fayers et al. 2001). All EORTC scales \& single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high/healthy level of

GHS/HRQoL Scale Score, Baseline

Group	Value	95% CI
Atezolizumab	54.70	± 22.00
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	55.25	± 21.06

GHS/HRQoL Scale Score, Week 6

Group	Value	95% CI
Atezolizumab	2.09	± 24.11
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	0.29	± 22.94

GHS/HRQoL Scale Score, Week 12

Group	Value	95% CI
Atezolizumab	2.76	± 23.42
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	1.85	± 19.94

GHS/HRQoL Scale Score, Week 18

Group	Value	95% CI
Atezolizumab	4.20	± 24.27
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	-0.42	± 19.52

GHS/HRQoL Scale Score, Week 24

Group	Value	95% CI
Atezolizumab	4.92	± 23.90
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	-1.72	± 18.82

GHS/HRQoL Scale Score, Week 30

Group	Value	95% CI
Atezolizumab	4.32	± 21.12
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	2.65	± 13.70

GHS/HRQoL Scale Score, Week 36

Group	Value	95% CI
Atezolizumab	8.20	± 23.55
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	-0.52	± 22.25

GHS/HRQoL Scale Score, Week 42

Group	Value	95% CI
Atezolizumab	6.17	± 24.98
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	1.19	± 19.02

Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score Secondary · Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)

The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 was scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or it

Dyspnoea, Baseline

Group	Value	95% CI
Atezolizumab	34.30	± 25.69
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	36.67	± 25.35

Dyspnoea, Week 6

Group	Value	95% CI
Atezolizumab	1.13	± 19.90
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	0.92	± 24.25

Dyspnoea, Week 12

Group	Value	95% CI
Atezolizumab	-0.23	± 24.28
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	-2.87	± 24.55

Dyspnoea, Week 18

Group	Value	95% CI
Atezolizumab	-4.78	± 18.93
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	0.90	± 23.33

Dyspnoea, Week 24

Group	Value	95% CI
Atezolizumab	-5.05	± 22.91
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	2.68	± 23.13

Dyspnoea, Week 30

Group	Value	95% CI
Atezolizumab	-5.34	± 22.00
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	1.52	± 25.03

Dyspnoea, Week 36

Group	Value	95% CI
Atezolizumab	-3.90	± 26.85
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	5.56	± 19.85

Dyspnoea, Week 42

Group	Value	95% CI
Atezolizumab	-11.11	± 26.63
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	-6.84	± 22.01

Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score Secondary · From baseline up to approximately 55 months

TTD with use of the EORTC was defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms was defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC sc

Dyspnoea

Group	Value	95% CI
Atezolizumab	NA	19.0 – NA
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	NA	8.3 – NA

Fatigue

Group	Value	95% CI
Atezolizumab	13.5	8.3 – NA
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	8.4	5.6 – NA

TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score Secondary · From baseline up to approximately 55 months

TTD with use of the EORTC was defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms was defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC sc

Cough

Group	Value	95% CI
Atezolizumab	NA	NA – NA
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	21.4	13.9 – NA

Chest Pain

Group	Value	95% CI
Atezolizumab	NA	NA – NA
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	NA	6.8 – NA

Dyspnoea

Group	Value	95% CI
Atezolizumab	17.3	9.6 – 34.2
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	8.3	5.5 – NA

Arm and/or Shoulder Pain

Group	Value	95% CI
Atezolizumab	21.3	13.6 – NA
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	13.9	8.6 – NA

Composite of Cough, Dyspnea and Chest Pain

Group	Value	95% CI
Atezolizumab	8.3	5.5 – 17.3
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	4.2	2.9 – 5.6

OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status Secondary · From randomization up to death from any cause (up to approximately 55 months)

OS was defined as the time between the date of randomization and the date of death due to any cause. OS was assessed in participants whose tumors express PD-L1 protein (i.e., tumor cell (TC) ≥1%) as measured by PD-L1 SP263 immunohistochemistry (IHC) assay. KM estimates were used to calculate the median.

Group	Value	95% CI
Atezolizumab	9.4	7.0 – 11.3
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	10.3	7.1 – 12.3

PFS as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status Secondary · From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)

PFS was defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first. PD was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. Investigator-assessed PFS was assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay. KM estimates were used to calculate the median.

Group	Value	95% CI
Atezolizumab	4.2	2.9 – 5.8
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	3.0	2.8 – 5.4

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 1 up to 90 days after last atezolizumab dose (up to approximately 62 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Atezolizumab

Serious: 147/300 (49%)

Deaths: 248/300

Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Serious: 54/147 (37%)

Deaths: 129/147

Serious adverse events (135 terms)

Reaction	System	Atezolizumab	Single Agent Chemotherapy …
Pneumonia	Infections and infestations	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Death	General disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	—	—
Lower respiratory tract infection	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Pyrexia	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Myelosuppression	Blood and lymphatic system disorders	—	—
Acute coronary syndrome	Cardiac disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Sudden cardiac death	General disorders	—	—
Immune-mediated hepatitis	Hepatobiliary disorders	—	—
Bronchitis	Infections and infestations	—	—

Other adverse events (33 terms — click to expand)

Reaction	System	Atezolizumab	Single Agent Chemotherapy …
Decreased appetite	Metabolism and nutrition disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Fatigue	General disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Weight decreased	Investigations	—	—
Hypothyroidism	Endocrine disorders	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Neutrophil count decreased	Investigations	—	—
Insomnia	Psychiatric disorders	—	—
Pneumonia	Infections and infestations	—	—
Blood creatinine increased	Investigations	—	—
White blood cell count decreased	Investigations	—	—
Headache	Nervous system disorders	—	—
Dizziness	Nervous system disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—

Most-reported serious reactions: Pneumonia, Pleural effusion, Pneumonitis, Death, Chronic obstructive pulmonary disease, Dyspnoea, Infective exacerbation of chronic obstructive airways disease, Lower respiratory tract infection.

Data from ClinicalTrials.gov NCT03191786 adverse events section.

Sponsor's own description

This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group \[ECOG\] performance status of 2-3).

Publications & conference data

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

1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
   Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
2. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
   Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
3. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.
   Lee SM, Schulz C, Prabhash K, Kowalski D, et al · · 2023 · cited 119× · PMID 37423228 · DOI 10.1016/s0140-6736(23)00774-2
4. Current Clinical Progress of PD-1/PD-L1 Immunotherapy and Potential Combination Treatment in Non-Small Cell Lung Cancer.
   Li JX, Huang JM, Jiang ZB, Li RZ, et al · · 2019 · cited 45× · PMID 31838881 · DOI 10.1177/1534735419890020
5. The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer.
   Low JL, Walsh RJ, Ang Y, Chan G, et al · · 2019 · cited 45× · PMID 31497071 · DOI 10.1177/1758835919870360
6. Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.
   Ferrara R, Imbimbo M, Malouf R, Paget-Bailly S, et al · · 2021 · cited 44× · PMID 33930176 · DOI 10.1002/14651858.cd013257.pub3
7. Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.
   Ferrara R, Imbimbo M, Malouf R, Paget-Bailly S, et al · · 2020 · cited 41× · PMID 33316104 · DOI 10.1002/14651858.cd013257.pub2
8. Current Trends in Cancer Immunotherapy.
   Filin IY, Solovyeva VV, Kitaeva KV, Rutland CS, et al · · 2020 · cited 35× · PMID 33348704 · DOI 10.3390/biomedicines8120621