A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT03563716
• Recruitment Status: Active, not recruiting
• First Posted: June 20, 2018
• Results First Posted: July 9, 2020
• Last Update Posted: May 25, 2023
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: April 17, 2018
• First Posted Date: June 20, 2018
• Results First Submitted Date: June 19, 2020
• Results First Posted Date: July 9, 2020
• Last Update Posted Date: May 25, 2023
• Actual Study Start Date: August 10, 2018
• Actual Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2020)

• Objective Response Rate (ORR) [ Time Frame: From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months) ]
  ORR, defined as a complete response (CR) or partial response (PR) on two consecutive occasions >/=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
• Progression Free Survival (PFS) [ Time Frame: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months) ]
  PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).

Original Primary Outcome Measures (submitted: June 19, 2018)

• Objective response rate (ORR) [ Time Frame: Up to 5 years ]
  ORR, defined as a complete response or partial response on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1
• Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
  PFS, 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

Current Secondary Outcome Measures (submitted: December 14, 2020)

• Duration of Objective Response (DOR) [ Time Frame: Up to 5 years ]
  DOR, defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  OS, defined as the time from randomization to death from any cause.
• Percentage of Participants With Adverse Events [ Time Frame: Up to 5 years ]
  An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event 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.
• Serum Concentrations of Tiragolumab [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years). ]
• Serum Concentrations of Atezolizumab [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years). ]
• Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years). ]

Original Secondary Outcome Measures (submitted: June 19, 2018)

• Duration of Objective Response (DOR) [ Time Frame: Up to 5 years ]
  DOR, 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
• Overall Survival (OS) [ Time Frame: Up to 5 years ]
  OS, defined as the time from randomization to death from any cause
• Percentage of Participants With Adverse Events [ Time Frame: Up to 5 years ]
• Serum concentrations of MTIG7192A or atezolizumab [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years). ]
• Perecentage of treatment-emergent anti-drug antibody-positive participants and anti-drug antibody-negative participants [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days), at treatment discontinuation visit (up to 5 years). ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• Official Title: A Phase II, Randomized, Blinded, Placebo-Controlled Study of Tiragolumab, An Anti-TIGIT Antibody, In Combination With Atezolizumab In Chemotherapy-Naïve Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
• Brief Summary: This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• Drug: Atezolizumab
  Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.
  Other Name: Tecentriq
• Drug: Tiragolumab
  Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
  Other Name: MTIG7192A
• Drug: Placebo
  Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Study Arms

• Placebo Comparator: Placebo + Atezolizumab
  Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Placebo
• Experimental: Tiragolumab + Atezolizumab
  Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab

• Publications *: Cho BC, Abreu DR, Hussein M, Cobo M, Patel AJ, Secen N, Lee KH, Massuti B, Hiret S, Yang JCH, Barlesi F, Lee DH, Ares LP, Hsieh RW, Patil NS, Twomey P, Yang X, Meng R, Johnson ML. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022 Jun;23(6):781-792. doi: 10.1016/S1470-2045(22)00226-1. Epub 2022 May 13.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 7, 2019): 135
• Original Estimated Enrollment (submitted: June 19, 2018): 120
• Estimated Study Completion Date: March 31, 2024
• Actual Primary Completion Date: June 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ECOG Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology
• No prior systemic treatment for locally advanced unresectable or metastatic NSCLC
• Tumor PD-L1 expression
• Measurable disease, as defined by RECIST v1.1
• Life expectancy >=12 weeks
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

Cancer-Specific Exclusions:

• Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to screening
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome

General Medical Exclusions:

• Pregnant and lactating women
• Significant cardiovascular disease
• Severe infections within 4 weeks prior to randomization
• Major surgical procedure other than for diagnosis within 4 weeks prior to randomization

Treatment-Specific Exclusions:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogeneic bone marrow transplantation or solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis
• Administration of a live, attenuated vaccine within 4 weeks prior to randomization

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Korea, Republic of, Serbia, Spain, Taiwan, United States
• Removed Location Countries: Brazil, Poland, Romania

Administrative Information

• NCT Number: NCT03563716
• Other Study ID Numbers: GO40290; 2018-000280-81 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: May 2023