Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy

NCT ID: NCT04471428

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 366 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2025-01-17

Brief Summary

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab given in combination with cabozantinib compared with docetaxel monotherapy in patients with metastatic NSCLC, with no sensitizing EGFR mutation or ALK translocation, who have progressed following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab + Cabozantinib

Participants received atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on Days 1-21 of each cycle.

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Cabozantinib will be administered orally, once daily at a dose of 40 mg on Days 1-21 of each cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Docetaxel

Participants received docetaxel on Day 1 of each 21-day cycle.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Docetaxel will be administered by IV infusion at a starting dose of 75mg/m2 on Day 1 of each 21-day cycle.

Interventions

Cabozantinib

Cabozantinib will be administered orally, once daily at a dose of 40 mg on Days 1-21 of each cycle.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Docetaxel

Docetaxel will be administered by IV infusion at a starting dose of 75mg/m2 on Day 1 of each 21-day cycle.

Intervention Type: DRUG

Other Intervention Names

Tecentriq

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed metastatic NSCLC
• Documented radiographic disease progression during or following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially for metastatic NSCLC
• Measurable disease per RECIST v1.1 outside CNS as assessed by investigator
• Known PD-L1 status or availability of tumor tissue for central PD-L1 testing
• ECOG Performance Status score of 0 or 1
• Recovery to baseline or Grade <=1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable on supportive therapy in the opinion of the investigator
• Adequate hematologic and end-organ function
• Negative HIV test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs,
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.

Exclusion Criteria

• Prior therapy with the following agents for NSCLC: Cabozantinib, Docetaxel, Combination of an anti-PD-L1/PD-1 antibody concurrently with a vascular endothelial growth factor (VEGF)R targeting tyrosine kinase inhibitor (TKI)
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Documentation of known sensitizing mutation in the EGFR gene or ALK fusion oncogene
• Patients with known ROS1 rearrangements, BRAF V600E mutations, or other actionable oncogenes with approved therapies if available
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more frequently than once monthly)
• Severe hepatic impairment
• Uncontrolled or symptomatic hypercalcemia
• Any other active malignancy at the time of initiation of study treatment or diagnosis of another malignancy within 3 years prior to initiation of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, incidental prostate cancer, or carcinoma in situ of the prostate, cervix, or breast
• Stroke, transient ischemic attack, myocardial infarction or other symptomatic ischemic events within 6 months of initiation of study treatment
• Significant vascular disease within 6 months of initiation of study treatment
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion on the investigator, could impact patient safety
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
• Current treatment with anti-viral therapy for HBV
• Major surgical procedure, other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Pregnant or lactating females, or intention of becoming pregnant during the treatment with atezolizumab in combination with cabozantinib in the experimental arm or during the treatment with docetaxel in the control arm, or within 5 months after the final dose of atezolizumab and/or 4 months after the final dose of cabozantinib, whichever is later.
• Ongoing Grade >= 2 sensory or motor neuropathy
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions: Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: Rash must cover < 10% of body surface area.
• Pharmacologically uncompensated, symptomatic hypothyroidism
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplantation
• Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor confirmation has been obtained. Patients who received mineralocorticoids, inhaled or low-dose systemic corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• Known allergy or hypersensitivity to any component of the cabozantinib formulation
• History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80
• Concomitant anticoagulation with coumarin agents, direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors
• History of risk factors for torsades de pointes
• Corrected QT interval corrected through use of Fridericia's formula (QTcF) > 480 ms per ECG within 14 days before initiation of study treatment
• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal antihypertensive treatment
• Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
• Abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess within 6 months before initiation of study treatment
• Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation
• Lesions invading major pulmonary blood vessels
• Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, coagulopathy, or other history of significant bleeding within 3 months before initiation of study treatment
• Serious non-healing wound/ulcer/bone fracture
• Malabsorption syndrome
• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption are also excluded.
• Requirement for hemodialysis or peritoneal dialysis
• Inability to swallow tablets

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Exelixis

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Stanford University

Palo Alto, California, United States

Kaiser Permanente - San Diego

San Diego, California, United States

Sansum Clinic

Santa Barbara, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Regional Cancer Care Associates

Bethesda, Maryland, United States

Minnesota Oncology Hematology

Saint Paul, Minnesota, United States

Consultants in Medical Oncology and Hematology

Broomall, Pennsylvania, United States

Charleston Oncology, P .A

Charleston, South Carolina, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah, United States

Oncology and Hematology Associates of Southwest Virginia, Inc.,-Blacksburg

Blacksburg, Virginia, United States

Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia, United States

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Townsville Hospital

Townsville, Queensland, Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia

Austin Hospital Olivia Newton John Cancer Centre

Heidelberg, Victoria, Australia

Affinity Oncology

Nedlands, Western Australia, Australia

Lkh-Univ. Klinikum Graz

Graz, , Austria

Ordensklinikum Linz Elisabethinen

Linz, , Austria

Lhk Feldkirch

Rankweil, , Austria

Lkh Salzburg - Univ. Klinikum Salzburg

Salzburg, , Austria

Medizinische Universität Wien

Vienna, , Austria

Institut Jules Bordet

Anderlecht, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

Clinique Ste-Elisabeth

Namur, , Belgium

CHU Angers,Service de Pneumologie

Angers, , France

CHU de Grenoble

Grenoble, , France

Hopital Dupuytren

Limoges, , France

Hôpital Saint Joseph

Marseille, , France

Centre Regional de Lutte contre le Cancer Val d Aurelle - Paul Lamarque

Montpellier, , France

Hopital Tenon

Paris, , France

Zentralklinik Bad Berka GmbH

Bad Berka, , Germany

Klinikum Koeln-Merheim

Cologne, , Germany

Universitaetsklinikum Giessen und Marburg GmbH

Giessen, , Germany

KRH Klinikum Siloah-Oststadt-Heidehaus

Hanover, , Germany

Universitaetsklinikum Giessen und Marburg

Marburg, , Germany

Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

Uoa Sotiria Hospital

Athens, , Greece

Henri Dunant Hospital

Athens, , Greece

Univ General Hosp Heraklion

Heraklion, , Greece

Euromedical General Clinic of Thessaloniki

Thessaloniki, , Greece

Ospedale Vito Fazzi

Lecce, Apulia, Italy

AORN Ospedali dei Colli Ospedale Monaldi

Napoli, Campania, Italy

Azienda Ospedaliero Universitaria di Parma

Parma, Emilia-Romagna, Italy

Ospedale Provinciale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, Italy

Irccs Centro Di Riferimento Oncologico (CRO)

Aviano, Friuli Venezia Giulia, Italy

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, Italy

Policlinico Umberto I, Oncologia B

Rome, Lazio, Italy

IRCCS AOU San Martino - IST

Genoa, Liguria, Italy

ASST Spedali Civili di Brescia

Brescia, Lombardy, Italy

Instituto Europeo di Oncologia

Milan, Lombardy, Italy

A.O.U Careggi

Florence, Tuscany, Italy

Hyogo Cancer Center

Hyōgo, , Japan

Sendai Kousei Hospital

Miyagi, , Japan

Osaka International Cancer Institute

Osaka, , Japan

National Cancer Center Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

Bydgoszcz, , Poland

SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4

Bytom, , Poland

Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice

Gliwice, , Poland

Szpital Wojewódzki im. Miko?aja Kopernika

Koszalin, , Poland

Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy

Otwock, , Poland

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, , Portugal

Hospital CUF Porto

Porto, , Portugal

IPO do Porto

Porto, , Portugal

CHVNG/E_Unidade 1

Vila Nova de Gaia, , Portugal

MEDSI Clinical Hospital on Pyatnitsky Highway

Moscow, Moscow Oblast, Russia

GBUZ Leningradskaya state clinical hospital

Saint Petersburg, Sankt-Peterburg, Russia

S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)

Saint Petersburg, Sankt-Peterburg, Russia

Regional Clinical Oncology Hospital

Yaroslavl, Yaroslavl Oblast, Russia

Chungbuk National University Hospital

Cheongju-si, , South Korea

National Cancer Center

Goyang-si, , South Korea

St. Vincent's Hospital

Gyeonggi-do, , South Korea

Ajou University Medical Center

Gyeonggi-do, , South Korea

Samsung Changwon Hospital

Gyeongsangnam-do, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Seoul St Mary's Hospital

Seoul, , South Korea

Ulsan University Hosiptal

Ulsan, , South Korea

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, , Spain

Institut Catala d Oncologia Hospital Duran i Reynals

L'Hospitalet de LLobegat, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Univ. Nuestra Señora de Valme

Seville, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Addenbrookes Hospital

Cambridge, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Barts & London School of Med

London, , United Kingdom

University College London Hospital

London, , United Kingdom

Chelsea & Westminster Hospital

London, , United Kingdom

Countries

United States; Australia; Austria; Belgium; France; Germany; Greece; Italy; Japan; Poland; Portugal; Russia; South Korea; Spain; United Kingdom

References

Neal J, Pavlakis N, Kim SW, Goto Y, Lim SM, Mountzios G, Fountzilas E, Mochalova A, Christoph DC, Bearz A, Quantin X, Palmero R, Antic V, Chun E, Edubilli TR, Lin YC, Huseni M, Ballinger M, Graupner V, Curran D, Vervaet P, Newsom-Davis T. CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy. J Clin Oncol. 2024 Jul 10;42(20):2393-2403. doi: 10.1200/JCO.23.02166. Epub 2024 Mar 29.

Reference Type: DERIVED

PMID: 38552197 (View on PubMed)

Xing P, Wang M, Zhao J, Zhong W, Chi Y, Xu Z, Li J. Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy. Thorac Cancer. 2021 Oct;12(20):2825-2828. doi: 10.1111/1759-7714.14113. Epub 2021 Aug 18.

Reference Type: DERIVED

PMID: 34409776 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://forpatients.roche.com/en/trials/cancer/lung-cancer/study-of-atezolizumab-in-combination-with-cabozantinib--77103.html

Related Info

Other Identifiers

GO41892

Identifier Type: -

Identifier Source: org_study_id