CONTACT-01: 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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04471428
Collaborator
Exelixis (Industry)
366
107
2
26
3.4
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
366 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Atezolizumab Given in Combination With Cabozantinib Versus Docetaxel Monotherapy in Patients With Metastatic Non-Small Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
Actual Study Start Date :
Oct 1, 2020
Actual Primary Completion Date :
May 10, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Atezolizumab + Cabozantinib

Participants will receive atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on days 1-21 of each cycle.

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

Drug: Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq
  • Active Comparator: Docetaxel

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

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

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 43 months]

      Overall survival (OS) after randomization, defined as the time from randomization to death from any cause.

    Secondary Outcome Measures

    1. PFS, as Determined by Investigator [Up to approximately 43 months]

      PFS after randomization, defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first).

    2. Confirmed Objective Response Rate (ORR), as Determined by Investigator [Up to approximately 43 months]

      Confirmed objective response rate (ORR), defined as the proportion of participants with a complete or partial response on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.

    3. Duration of response (DOR), as Determined by Investigator [Up to approximately 43 months]

      Duration of response (DOR) for participants with confirmed ORR, defined as the time from the 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).

    4. Time to Confirmed Deterioration in Patient-Reported Physical Functioning (PF) [Up to approximately 43 months]

      Time to confirmed deterioration in patient-reported physical functioning (PF) as measured by the corresponding scores from the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30).

    5. Time to Confirmed Deterioration in Patient-Reported Global Health Status (GHS) [Up to approximately 43 months]

      Time to confirmed deterioration in patient-reported Global Health Status (GHS) as measured by the corresponding scores from the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30).

    6. PFS Rates Assessed by Investigator [6 months and 1 year]

    7. OS Rates [1 and 2 years]

    8. Percentage of Participants With Adverse Events [Up to approximately 43 months]

    9. Minimum Serum Concentration (Cmin) of Atezolizumab [Predose and postdose on Day 1 of Cycle 1; and Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)]

    10. Maximum Serum Concentration (Cmax) of Atezolizumab [Predose and postdose on Day 1 of Cycle 1; and Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)]

    11. Minimum Serum Concentration (Cmin) of Cabozantinib [Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)]

    12. Maximum Serum Concentration (Cmax) of Cabozantinib [Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)]

    13. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [Predose on Day 1 of Cycle 1 (each cycle is 21 days)]

    14. Number of ADAs to Atezolizumab After Treatment [Predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 (each cycle is 21 days)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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, Wegener granulomatosis, 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford University Palo Alto California United States 94305
    2 Kaiser Permanente - San Diego San Diego California United States 92120
    3 Sansum Clinic Santa Barbara California United States 93105
    4 Rocky Mountain Cancer Centers Denver Colorado United States 80220
    5 Regional Cancer Care Associates Bethesda Maryland United States 20817
    6 Karmanos Cancer Center Detroit Michigan United States 48201
    7 Minnesota Oncology Hematology Saint Paul Minnesota United States 55102
    8 Oncology Associates of Oregon, P.C Eugene Oregon United States 97401
    9 Consultants in Medical Oncology and Hematology Broomall Pennsylvania United States 19008
    10 Charleston Oncology, P .A Charleston South Carolina United States 29414
    11 Texas Oncology - Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    12 Huntsman Cancer Institute at The University of Utah Salt Lake City Utah United States 84112
    13 Virginia Cancer Specialists (Fairfax) - USOR Fairfax Virginia United States 22031
    14 Oncology and Hematology Associates of Southwest Virginia, Inc.,-Blacksburg Roanoke Virginia United States 24014
    15 Royal North Shore Hospital; Oncology St. Leonards New South Wales Australia 2065
    16 Townsville Hospital Townsville Queensland Australia 4810
    17 Flinders Medical Centre Bedford Park South Australia Australia 5042
    18 Austin Hospital Olivia Newton John Cancer Centre Heidelberg Victoria Australia 3084
    19 Affinity Oncology Nedlands Western Australia Australia 6009
    20 LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie Graz Austria 8036
    21 Ordensklinikum Linz Elisabethinen Linz Austria 4020
    22 Lhk Feldkirch; Interne Medizin Abt. Rankweil Austria 6830
    23 Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt. Salzburg Austria 5020
    24 Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie Wien Austria 1090
    25 Institut Jules Bordet Anderlecht Belgium 1070
    26 Cliniques Universitaires St-Luc Bruxelles Belgium 1200
    27 UZ Gent Gent Belgium 9000
    28 Clinique Ste-Elisabeth Namur Belgium 5000
    29 Clinique de l'Europe Amiens France 80090
    30 CHU Angers,Service de Pneumologie Angers France 49933
    31 CHU de Grenoble Grenoble France 38043
    32 Hopital Dupuytren; Pneumologie Limoges France 87042
    33 Hôpital Saint Joseph; Oncologie Medicale Marseille France 13285
    34 Centre Regional de Lutte contre le Cancer Val d Aurelle - Paul Lamarque; Service d oncologie Montpellier France 34298
    35 Centre Hospitalier de Mulhouse - Hopital Emile Muller Mulhouse France 68070
    36 Hopital Tenon;Pneumologie Paris France 75970
    37 Zentralklinik Bad Berka GmbH; Pneumologie Bad Berka Germany 99437
    38 Kliniken Essen Mitte Evang. Huyssens Stiftung/Knappschaft GmbH Essen Germany 45136
    39 Universitaetsklinikum Giessen und Marburg GmbH; Medizinische Klinik IV und V Gießen Germany 35392
    40 KRH Klinikum Siloah-Oststadt-Heidehaus Hannover Germany 30459
    41 Klinikum Koeln-Merheim; Lungenklinik Köln Germany 51109
    42 Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik Mainz Germany 55131
    43 Universitaetsklinikum Giessen und Marburg Marburg Germany 35043
    44 Brüderkrankenhaus St. Josef Paderborn Paderborn Germany 33098
    45 Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine Athens Greece 115 22
    46 Henri Dunant Hospital; Oncology Dept. Athens Greece 115 26
    47 Uoa Sotiria Hospital; Oncology Athens Greece 115 27
    48 Univ General Hosp Heraklion; Medical Oncology Heraklion Greece 711 10
    49 Euromedical General Clinic of Thessaloniki; Oncology Department Thessaloniki Greece 546 45
    50 AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico Napoli Campania Italy 80131
    51 Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica Bologna Emilia-Romagna Italy 40138
    52 Azienda Ospedaliero Universitaria di Parma Parma Emilia-Romagna Italy 43126
    53 Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica Ravenna Emilia-Romagna Italy 48100
    54 Irccs Centro Di Riferimento Oncologico (CRO) Aviano Friuli-Venezia Giulia Italy 33081
    55 Azienda Ospedaliera San Camillo Forlanini Roma Lazio Italy 00152
    56 Policlinico Umberto I, Oncologia B Roma Lazio Italy 00161
    57 IRCCS AOU San Martino - IST Genova Liguria Italy 16132
    58 ASST Spedali Civili di Brescia Brescia Lombardia Italy 25123
    59 Instituto Europeo di Oncologia Milan Lombardia Italy 20141
    60 Istituto Clinico Humanitas Rozzano (MI) Lombardia Italy 20089
    61 Ospedale Vito Fazzi Lecce Puglia Italy 73100
    62 A.O.U Careggi Florence Toscana Italy 50124
    63 Hyogo Cancer Center Hyogo Japan 673-0021
    64 Sendai Kousei Hospital Miyagi Japan 980-0873
    65 Osaka International Cancer Institute Osaka Japan 541-8567
    66 National Cancer Center Hospital Tokyo Japan 104-0045
    67 The Cancer Institute Hospital of JFCR Tokyo Japan 135-8550
    68 Chungbuk National University Hospital Cheongju-si Korea, Republic of 28644
    69 National Cancer Center Goyang-si Korea, Republic of 10408
    70 St. Vincent's Hospital Gyeonggi-do Korea, Republic of 16247
    71 Ajou University Medical Center Gyeonggi-do Korea, Republic of 16499
    72 Samsung Changwon Hospital Gyeongsangnam-do Korea, Republic of 51353
    73 Gachon University Gil Medical Center Incheon Korea, Republic of 21565
    74 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    75 Korea University Anam Hospital Seoul Korea, Republic of 02841
    76 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    77 Asan Medical Center Seoul Korea, Republic of 05505
    78 Seoul St Mary's Hospital Seoul Korea, Republic of 06591
    79 Ulsan University Hosiptal Ulsan Korea, Republic of 44033
    80 Centrum Onkologii im. Prof. Franciszka Łukaszczyka; Ambulatorium Chemioterapii Bydgoszcz Poland 85-796
    81 SP ZOZ Wojewódzki Szpital Specjalistyczny nr 4; Oddzial Onkologii Klinicznej Bytom Poland 41-902
    82 Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter. Gliwice Poland 44-101
    83 Szpital Wojewódzki im. Mikołaja Kopernika; Oddział Dzienny Chemioterapii Koszalin Poland 75-581
    84 Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii Otwock Poland 05-400
    85 Hospital Pulido Valente; Servico de Pneumologia Lisboa Portugal 1796-001
    86 Centro Hospitalar do Porto - Hospital de Santo António; Oncologia Porto Portugal 4099-001
    87 Hospital CUF Porto; Servico Pneumologia Porto Portugal 4100-180
    88 IPO do Porto; Servico de Oncologia Medica Porto Portugal 4200-072
    89 CHVNG/E_Unidade 1; Servico de Pneumologia Vila Nova de Gaia Portugal 4434-502
    90 Regional Clinical Oncology Hospital Yaroslavl Jaroslavl Russian Federation 150054
    91 MEDSI Clinical Hospital on Pyatnitsky Highway; Department of antitumor drug therapy Moscow Moskovskaja Oblast Russian Federation 143422
    92 S-Pb clinical scientific practical center of specialized kinds of medical care (oncological) Saint-Petersburg Russian Federation 197758
    93 GBUZ Leningradskaya state clinical hospital St. Petersburg Russian Federation 194291
    94 Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia A Coruña LA Coruña Spain 15006
    95 Vall d´Hebron Institute of Oncology (VHIO), Barcelona Barcelona Spain 08035
    96 Institut Catala d Oncologia Hospital Duran i Reynals Barcelona Spain 08908
    97 Hospital Universitario La Paz; Servicio de Oncologia Madrid Spain 28046
    98 Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia Sevilla Spain 41014
    99 Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia Valencia Spain 46015
    100 Hospital Universitari i Politecnic La Fe; Oncologia Valencia Spain 46026
    101 Addenbrookes Hospital Cambridge United Kingdom CB2 0QQ
    102 Beatson West of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    103 Huddersfield Royal Infirmary; The Learning Centre Huddersfield United Kingdom HD3 3EA
    104 Barts & London School of Med; Medical Oncology London United Kingdom EC1A 7BE
    105 University College London Hospital London United Kingdom NW1 - 2PG
    106 Royal Free Hospital London United Kingdom NW3 2QS
    107 Chelsea & Westminster Hospital London United Kingdom SW10 9NH

    Sponsors and Collaborators

    • Hoffmann-La Roche
    • Exelixis

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04471428
    Other Study ID Numbers:
    • GO41892
    First Posted:
    Jul 15, 2020
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022