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 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03735121
• Other study ID #: BP40657
• Secondary ID: 2018-002328-18
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 14, 2018
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 438
• Est. completion date: December 31, 2024
• Est. primary completion date: April 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered as per the schedule specified in arm or cohort.
• rHuPH20
rHuPH20 will be administered as per the scheduled specified in the cohort for Part 1.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Consultorio Dr. Miguel Angel Escudero	Salta
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	INCA 1- Instituto Nacional de Câncer X	Rio de Janeiro	RJ
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Chile	Bradford Hill Centro de Investigaciones Clinicas	Recoleta
Chile	James Lind Centro de Investigación Del Cáncer	Temuco
Chile	ONCOCENTRO APYS; Oncología	Vina Del Mar
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	West China Hospital - Sichuan University	Chengdu City
China	Cancer Center of Guangzhou Medical University	Guangzhou
China	Sir Run Run Shaw Hospital Zhejiang University	Hangzhou City
China	Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department	Hangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Jinan Central Hospital	Jinan City
China	Tianjin Cancer Hospital	Tianjin
China	Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center	Wuhan
China	Henan Cancer Hospital	Zhengzhou
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
France	Aphm; Cpcet	Marseille
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
Greece	General Hospital "G.Papanikolaou"; Pulmonogy Clinic	Asvestochori
Greece	Sotiria Hospital	Athens
Guatemala	Hospital El Pilar	Ciudad de Guatemala
Guatemala	INTEGRA Cancer Institute	Ciudad de Guatemala
Guatemala	Oncomedica	Guatemala
Guatemala	Grupo Angeles	Guatemala City
Hungary	Matrai Gyogyintezet	Matrahaza
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Székesfehérvár
Hungary	Református Pulmonológiai Centrum; Oncology Department	Törökbálint
Italy	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia
Italy	IRCCS Istituto Clinico Humanitas; Oncologia	Rozzano (MI)	Lombardia
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Centre; Medical Oncology	Seoul
Latvia	Riga East Clinical University Hospital Latvian Oncology Centre	Riga
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Cuidados oncologicos	Querétaro	Queretaro
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
New Zealand	Christchurch Clinical Studies Trust Ltd	Christchurch
New Zealand	Waikato Hospital - Cancer and Blood Research Trials Unit; Regional Cancer Centre	Hamilton
New Zealand	Tauranga Hospital, Clinical Trials Unit; BOP Clinical School	Tauranga
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional	Lima
Peru	Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel	Lima
Peru	Oncosalud Sac; Oncología	Lima
Poland	Regionalny Szpital Specjalistyczny im. W. Bieganskiego; Oddzial Onkologii Klinicznej	Grudzi?dz
Poland	Centrum Terapii Wspolczesnej	Lodz
Poland	Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy; Dept of Pulmonology & subdiv. of oncology	Otwock
Poland	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz	Warszawa
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk	Moskovskaja Oblast
Russian Federation	SBIH Kaluga Region Clinical Oncology Dispensary	Kaluga
Russian Federation	FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF	Moscow	Moskovskaja Oblast
Russian Federation	MEDSI Clinical Hospital on Pyatnitsky Highway; Department of antitumor drug therapy	Moscow	Moskovskaja Oblast
Russian Federation	Murmansk Regional Clinical Hospital named after P.A. Bayandin	Murmansk
Russian Federation	Filial #1 Regional Oncology Dispensary of Nizhniy Novgorod	Nizhny Novgorod	Niznij Novgorod
Russian Federation	Multidisciplinary clinic Reaviz	Samara
Russian Federation	Mordovia State University	Saransk	Mordovija
South Africa	Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept	Cape Town
South Africa	Richards Bay Oncology Centre	KwaZulu Natal
South Africa	Wilgers Oncology Centre	Pretoria
South Africa	Sandton Oncology Medical Group	Sandton
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Vajira Hospital	Bangkok
Thailand	Prapokklao Hospital	Chanthaburi
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Medicine	ChiangMai
Thailand	Prince of Songkla University; Division of Pulmonary Disease, Department of Medicine	Hat Yai
Thailand	Khonkaen Hospital	Khonkaen
Thailand	Udonthani Cancer Hospital, Udonthani	Muang,Udonthani
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department	Istanbul
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Ukraine	Municipal Institution City Clinical Hospital #4 of Dnipro City Council	Dnipropetrovsk	Katerynoslav Governorate
Ukraine	Ivano-Frankivsk Regional Oncology Center	Ivano-Frankivsk
Ukraine	Communal Non profit Enterprise Regional Center of Oncology; Oncosurgical dept of thoracic organs	Kharkiv	Kharkiv Governorate
Ukraine	RCI Sumy Regional Clinical Oncological Dispensary	Sumy
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	St James Hospital; Dept of Oncology/Hematology	Leeds

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Brazil,  Chile,  China,  Costa Rica,  France,  Greece,  Guatemala,  Hungary,  Italy,  Korea, Republic of,  Latvia,  Mexico,  New Zealand,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Serum Trough Concentration (Ctrough) of Atezolizumab at Cycle 1		Pre-dose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
Primary	Part 2: Observed Serum Ctrough of Atezolizumab at Cycle 1		Predose on Day 1 of Cycle 2 (Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2)
Primary	Part 2: Area Under the Concentration-Time Curve From Time Zero to 21 Days (AUC 0-21 d) at Cycle 1		From start of dosing up to Day 21 in Cycle 1 (Cycle length= 21 days)
Secondary	Part 1: Maximum Observed Serum Concentration (Cmax) of Atezolizumab		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)
Secondary	Part 1: Time to Maximum Serum Concentration (Tmax) of Atezolizumab		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)
Secondary	Part 1: Area Under the Concentration-time Curve (AUClast) of Atezolizumab		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)
Secondary	Part 1: Serum Atezolizumab Concentration at Specified Timepoint During SC Administration	Cycle length =21 days for cohorts 1 and 3 and 14 days for cohort 2. Day=D; Cycle=C.	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
Secondary	Part 1: Percentage of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0).	Baseline up to data cutoff date for primary analysis, April 26, 2022 (up to approximately 17 months)
Secondary	Part 2: Percentage of Participants With AEs	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 5.0 (NCI-CTCAE, v5.0).	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)
Secondary	Part 2: Model Predicted Ctrough of Atezolizumab at Cycle 1		Cycle 1 (Cycle length=21 days)
Secondary	Part 2: Model Predicted Ctrough at Steady State (Cthrough,ss) of Atezolizumab	1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo.	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)
Secondary	Part 2: Model Predicted AUC at Steady State (AUCss) of Atezolizumab	1 cycle=21 days Abbreviations used-Cycle=C; Day =D; Atezolizumab=atezo	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)
Secondary	Part 2: Objective Response Rate (ORR)	ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR.	From treatment initiation until disease progression or loss of clinical benefit (Up to approximately 72 months).
Secondary	Part 2: Progression-Free Survival (PFS)	PFS is defined as the time from study start to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or or death from any cause (whichever occurs first).	From study start to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 72 months).
Secondary	Part 2: Overall Survival (OS)	OS defined as the time from study entry to death from any cause.	From study start to death from any cause (Up to approximately 72 months)
Secondary	Part 2: Duration of Response (DOR)	DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. Objective response is defined as the percentage of participants having a CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters in the absence of CR.	From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 72 months)
Secondary	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	EORTC IL57 questionnaire has10 items and covers 3 scales: physical functioning (PF), role functioning (RF) & global health status/quality of life (GHS/QoL) & 1 item from EORTC Item Library. PF scale has 5 items evaluating the extent to which participants have trouble doing strenuous activities; taking long walks & short walks; need to stay in bed or a chair; need help with eating, dressing, bathing/using toilet. RF scale has 2 items evaluating extent to which participants are limited in doing work & pursuing leisure activities in previous week. GHS/QoL scale has 2 items evaluating participants' overall health & QoL in previous week. Questions are answered on a 4-point Likert scale (where 1="Not at all" to 4="Very much") for physical and role functioning & a 7-point scale (where 1="Very poor" to 7="Excellent") for GHS/QoL. For each scale, mean of the items are linearly transformed to obtain scores from 0-100, where 100 =best possible score. Higher score = better outcome.	From Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
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)	Modified SWT scale of the CTSQ consist of seven items that measures seven domains related to satisfaction with cancer therapy. These include worthwhile, difficulty, benefits, feelings about side effects, form of therapy, overall satisfaction, and if participants would choose the therapy taking everything into consideration. Each domain is rated on a 5-point scale, with 1 representing the worst response and 5 representing the best response, except in the case of one reverse-scored item. mean of the items are linearly transformed to obtain scores from 0-100, where 100 =best possible score Higher scores are associated with higher satisfaction.	Day 1 Cycle 3 or at treatment discontinuation visit (Up to approximately 72 months)
Secondary	Part 2: Overall Patient-reported AE's Burden Over Time, Assessed by the Treatment-related Symptom Burden Item From the EORTC IL57	The overall patient-reported AE burden was assessed using the a single item from the EORTC IL57 questionnaire i.e To what extent have you been troubled with side-effects from your treatment?. The questions is answered on a 4-point Likert scale where 1="Not at all" to 4="Very much". Higher scores indicates greater AE burden.	Day 1 of Cycles 1-6 and then every other cycle up to treatment discontinuation visit (Up to approximately 72 months)
Secondary	Part 2: Percentage of Participants With Ant-Drug Antibodies (ADAs) to Atezolizumab After SC or IV Administration		From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months).
Secondary	Part 2: Percentage of Participants With ADAs to rHuPH20 After SC Administration Relative to the Prevalence of ADAs at Baseline		From first dose of atezolizumab up to treatment discontinuation visit (Up to approximately 72 Months)
Secondary	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	The HCP Subcutaneous Versus IV Perspective Questionnaire consists of five items evaluating the number of atezolizumab SC and IV administrations done, convenience, potential time savings, and overall satisfaction with atezolizumab SC and atezolizumab IV, as well as reasons for HCP-reported satisfaction or dissatisfaction.	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)
Secondary	Part 2: Convenience, Ease of Administration, and Overall Satisfaction With Atezolizumab SC Assessed Using HCP Subcutaneous Perspective Questionnaire	The HCP Subcutaneous Perspective Questionnaire consists of five items evaluating the convenience, ease of administration and overall satisfaction with atezolizumab SC, as well as reasons for HCP-reported satisfaction or dissatisfaction.	After HCP has completed administering at least 3 doses of atezolizumab SC across all participants in Part 2 (Up to approximately 72 months)