Clinical trial NCT03735121: A Study to Investigate Atezolizumab Subcutaneous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Randomized, Multicenter, Phase Ib/III Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous Compared With Atezolizumab Intravenous in Patients With Previously Treated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-11-08
Enrollment: 438
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Intervention study model can be sequential or in parallel.
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1
timeFrame: Pre-dose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
measure: Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1
timeFrame: Predose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
measure: Part 2: Area Under the Concentration-Time Curve From Time Zero to 21 Days (AUC 0-21 d) at Cycle 1
timeFrame: From start of dosing up to Day 21 in Cycle 1 (Cycle length= 21 days)
Secondary outcomes:
measure: Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab
timeFrame: Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
measure: Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab
timeFrame: Predose and post dose on Day 1 of Cycle 1 and post dose on Days 3 and 8 of Cycle 1 (Cycle length = 21 days for cohorts 1 and 3 and 14 days for cohort 2)
measure: Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab
timeFrame: Predose and up to 21 days post dose in Cycle 1 for cohorts 1 and 3 and from predose up to 14 days post last dose in Cycle 1 for cohort 2 (Cycle length= 21 days for cohorts 1 and 3 and 14 days for cohort 2)
measure: Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration
timeFrame: Cohort 1: Pre&postdose:D1 &postdose: D3,8 of C1; Cohort 2: Pre&postdose: D1 of C1,3 & postdose: D3,8 of C1, Predose: D1 of C2; Cohort 3: Pre& postdose: D1 of C1,2 & postdose: D3,8 of C1, D2,4& 9 of C2& pre dose:D1 of C3
measure: Part 1: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to data cutoff date for primary analysis, April 26, 2022 (up to approximately 17 months)
measure: Part 2: Percentage of Participants With AEs
timeFrame: From signing of informed consent form (ICF) until 30 days after last dose of study drug administration in Part 2 (Up to approximately 72 months)
measure: Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1
timeFrame: Cycle 1 (Cycle length=21 days)
measure: Part 2: Model Predicted Ctrough at Steady State (Cthrough,ss) of Atezolizumab
timeFrame: Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)
measure: Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab
timeFrame: Atezo SC: Pre&postdose C1D1, postdose C1 Days 2,4,8, Pre&postdose C2,D1 and Predose on D1 of C3,4,8,12 and 16 ; Atezo IV: Pre&postdose on C1D1, postdose C1 Days 2,4,8; Pre&postdose C2D1, Predose on D1 of C3,4,8,12, and 16 (up to approximately 16 months)
measure: Part 2: Objective Response Rate (ORR)
timeFrame: From treatment initiation until disease progression or loss of clinical benefit (Up to approximately 72 months).
measure: Part 2: Progression-Free Survival (PFS)
timeFrame: From study start to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 72 months).
measure: Part 2: Overall Survival (OS)
timeFrame: From study start to death from any cause (Up to approximately 72 months)
measure: Part 2: Duration of Response (DOR)
timeFrame: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 72 months)
measure: Part 2: Functioning and Global Health Status Over Time, as Assessed by European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)57
timeFrame: From Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
measure: Part 2: Overall Satisfaction With Treatment Over Time, Assessed by the Modified Satisfaction With Therapy (SWT) Scale of the Cancer Therapy Satisfaction Questionnaire (CTSQ)
timeFrame: Day 1 Cycle 3 or at treatment discontinuation visit (Up to approximately 72 months)
measure: Part 2: Overall Patient-reported AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57
timeFrame: Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
measure: Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration
timeFrame: From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months).
measure: Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration Relative to the Prevalence of ADAs at Baseline
timeFrame: From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months)
measure: Part 2: Convenience, Potential Time Savings, and Overall Satisfaction With Atezolizumab SC Compared With Atezolizumab IV as Assessed by the Health Care Professional (HCP) SC Versus IV Perspective Questionnaire
timeFrame: After HCP has completed administering at least 3 doses of atezolizumab SC and IV across all participants in Part 2 (Up to approximately 72 months)
measure: Part 2: Convenience, Ease of Administration, and Overall Satisfaction With Atezolizumab SC Assessed Using HCP Subcutaneous Perspective Questionnaire
timeFrame: After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 72 months)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Salta
country: Argentina
facility: Consultorio Dr. Miguel Angel Escudero
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: Rio de Janeiro
country: Brazil
facility: INCA 1- Instituto Nacional de Câncer X
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: Temuco
country: Chile
facility: James Lind Centro de Investigación Del Cáncer
city: Vina Del Mar
country: Chile
facility: Oncocentro Apys
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Chengdu City
country: China
facility: West China Hospital - Sichuan University
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University
city: Jinan City
country: China
facility: Jinan Central Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: San Jose
country: Costa Rica
facility: Clinica CIMCA
city: San Jose
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Marseille
country: France
facility: APHM
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau
city: Asvestochori
country: Greece
facility: General Hospital "G.Papanikolaou"
city: Athens
country: Greece
facility: Sotiria Hospital
city: Ciudad de Guatemala
country: Guatemala
facility: INTEGRA Cancer Institute
city: Ciudad de Guatemala
country: Guatemala
facility: Hospital El Pilar
city: Guatemala City
country: Guatemala
facility: Grupo Angeles
city: Guatemala
country: Guatemala
facility: Oncomedica
city: Matrahaza
country: Hungary
facility: Matrai Gyogyintezet
city: Törökbálint
country: Hungary
facility: Református Pulmonológiai Centrum
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
state: Lombardia
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centre
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital Latvian Oncology Centre
city: Querétaro
country: Mexico
facility: Cuidados oncologicos
state: Queretaro
city: Auckland
country: New Zealand
facility: Auckland City Hospital, Cancer and Blood Research
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust Ltd
city: Hamilton
country: New Zealand
facility: Waikato Hospital - Cancer and Blood Research Trials Unit
city: Tauranga
country: New Zealand
facility: Tauranga Hospital, Clinical Trials Unit
city: Arequipa
country: Peru
facility: Centro Medico Monte Carmelo
city: Lima
country: Peru
facility: Clínica San Gabriel
city: Lima
country: Peru
facility: Oncosalud Sac
city: Lima
country: Peru
facility: Clinica Internacional, Sede San Borja
city: Grudzi?dz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. W. Bieganskiego
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
city: Saransk
country: Russian Federation
facility: Mordovia State University
state: Mordovija
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Oncology Dispensary
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: MEDSI Clinical Hospital on Pyatnitsky Highway
state: Moskovskaja Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod
state: Niznij Novgorod
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Clinical Hospital named after P.A. Bayandin
city: Samara
country: Russian Federation
facility: Multidisciplinary clinic Reaviz
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital ( Uni of Capetown )
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre
city: Sandton
country: South Africa
facility: Sandton Oncology Medical Group
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Rajavithi Hospital
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital
city: ChiangMai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Hat Yai
country: Thailand
facility: Prince of Songkla University
city: Muang,Udonthani
country: Thailand
facility: Udonthani Cancer Hospital, Udonthani
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Ankara
country: Turkey
facility: Ankara Bilkent City Hospital
city: Istanbul
country: Turkey
facility: Kartal Dr Lutfi Kirdar Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital
city: Dnipropetrovsk
country: Ukraine
facility: Municipal Institution City Clinical Hospital #4 of Dnipro City Council
state: Katerynoslav Governorate
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Felip E, Burotto M, Zvirbule Z, Herraez-Baranda LA, Chanu P, Kshirsagar S, Maiya V, Chan P, Pozzi E, Marchand M, Monchalin M, Tanaka K, Tosti N, Wang B, Restuccia E. Results of a Dose-Finding Phase 1b Study of Subcutaneous Atezolizumab in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1142-1155. doi: 10.1002/cpdd.936. Epub 2021 Mar 31.