Phase 3
N=438
A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03735121 ↗Enrolled (actual)
438
Serious AEs
22.6%
Results posted
Jun 2023
Primary outcome: Primary: Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1 — 121; 77.5; 78.3 micrograms per milliliter (μg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (Drug); rHuPH20 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1 |
121; 77.5; 78.3 | — |
| PRIMARY Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1 |
85.4; 89.4 | — |
| PRIMARY Part 2: Area Under the Concentration-Time Curve From Time Zero to 21 Days (AUC 0-21 d) at Cycle 1 |
3327.9; 2907.1 | — |
| SECONDARY Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab |
251; 129; 181 | — |
| SECONDARY Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab |
3.02; 3.45; 3.92 | — |
| SECONDARY Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab |
3870; 1410; 2820 | — |
| SECONDARY Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration |
NA; NA; NA; 116; 61.7; 108 | — |
| SECONDARY Part 1: Percentage of Participants With Adverse Events (AEs) |
100; 86.7; 84.6 | — |
| SECONDARY Part 2: Percentage of Participants With AEs |
85.5; 89.9 | — |
| SECONDARY Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1 |
88.7; 97.2 | — |
| SECONDARY Part 2: Model Predicted Ctrough at Steady State (Ctrough,ss) of Atezolizumab |
179; 205 | — |
| SECONDARY Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab |
6107; 6163 | — |
| SECONDARY Part 2: Objective Response Rate (ORR) |
10.5; 11.0 | 0.8757 |
| SECONDARY Part 2: Progression-free Survival (PFS) |
2.9; 2.8 | 0.6906 |
| SECONDARY Part 2: Overall Survival (OS) |
10.1; 10.9 | 0.9766 |
| SECONDARY Part 2: Duration of Response (DOR) |
11.2; 15.1 | 0.8375 |
| SECONDARY Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL) 57 Physical Functioning Score |
74.53; 72.15; -6.23; -4.23; -4.55; -4.99 | — |
| SECONDARY Part 2: Change From Baseline in EORTC IL57 Role Functioning Score |
74.93; 74.86; 0.31; -4.36; -3.29; -4.67 | — |
| SECONDARY Part 2: Change From Baseline in EORTC IL57 Global Health Status Score |
66.52; 63.50; -3.54; -2.48; -2.91; -1.83 | — |
| SECONDARY Part 2: Overall Satisfaction With Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ) |
77.29; 75.56; 50.67; 61.21 | — |
| SECONDARY Part 2: Percentage of Participants by Their Responses to AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57 |
49.6; 56.7; 36.3; 28.6; 8.0; 10.1 | — |
| SECONDARY Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration |
14.3; 20.6 | — |
| SECONDARY Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration |
5.7 | — |
| SECONDARY Part 2: Percentage of Health Care Professionals (HCPs) by Their Response to Question 2 of HCP SC Versus IV Perspective Questionnaire |
24.0; 16.0; 26.0; 12.0; 22.0 | — |
| SECONDARY Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Versus IV Perspective Questionnaire |
74.0; 14.0; 12.0 | — |
| SECONDARY Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Versus IV Perspective Questionnaire |
32.0; 38.0; 30.0 | — |
| SECONDARY Part 2: Percentage of HCPs by Their Response to Question 2 of the HCP SC Perspective Questionnaire |
78.6; 14.3; 7.1 | — |
| SECONDARY Part 2: Percentage of HCPs by Their Response to Question 3 of the HCP SC Perspective Questionnaire |
54.8; 34.5; 10.7 | — |
| SECONDARY Part 2: Percentage of HCPs by Their Response to Question 4 of the HCP SC Perspective Questionnaire |
34.5; 50.0; 13.1; 2.4 | — |
Summary
This study will evaluate the pharmacokinetics, safety, and efficacy of atezolizumab subcutaneous (SC) compared with atezolizumab intravenous (IV) in participants with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who have not been exposed to cancer immunotherapy (CIT) and for whom prior platinum-based therapy has failed. The study is comprised of two parts, as follows: A dose-finding part (Part 1, Phase Ib) will aim to identify the dose of atezolizumab SC to be tested in Part 2. A dose-confirmation part (Part 2, Phase III, randomized) will aim to confirm that the dose moved forward from Part 1 yields drug exposure that is comparable to that of atezolizumab IV.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically documented locally advanced or metastatic NSCLC
- Prior platinum-containing regimen or disease recurrence ≤ 6 months since prior platinum-based adjuvant/neoadjuvant regimen.
- Measurable disease as defined by RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy ≥12 weeks
- Adequate hematologic and end-organ function
Additional Inclusion Criteria (Part 2 Only) • Availability of tissue and known epidermal growth factor receptor (EGFR) status
Exclusion Criteria
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Uncontrolled or symptomatic hypercalcemia
- Pregnancy or breastfeeding
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
- Severe infection ≤ 4 weeks
- Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to study treatment
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with a live, attenuated vaccine ≤ 4 weeks
- Treatment with systemic immunostimulatory agents ≤ 4 weeks or 5 half-lives of the drug
- Treatment with systemic immunosuppressive medication ≤ 2 weeks
Additional Exclusion Criteria (Part 2 Only)
- Tested tumor programmed death-ligand-1 (PD-L1) expression status with an intention to treat the patient if positive
Data sourced from ClinicalTrials.gov (NCT03735121). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.