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A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

NCT04619797

Description:

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase:- Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer
  • Official Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: BO42592
  • SECONDARY ID: 2020-002851-39
  • NCT ID: NCT04619797

Conditions

  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
TiragolumabMTIG7192ATiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
AtezolizumabTecentriqTiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin
PemetrexedPlacebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
CarboplatinPlacebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
CisplatinPlacebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
Tiragolumab Matching PlaceboPlacebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin
PembrolizumabPlacebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin

Purpose

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase:- Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).

Trial Arms

NameTypeDescriptionInterventions
Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or CisplatinExperimentalInduction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.
  • Tiragolumab
  • Atezolizumab
  • Pemetrexed
  • Carboplatin
  • Cisplatin
Placebo+Pembrolizumab+Pemetrexed+Carboplatin or CisplatinPlacebo ComparatorInduction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.
  • Pemetrexed
  • Carboplatin
  • Cisplatin
  • Tiragolumab Matching Placebo
  • Pembrolizumab

Eligibility Criteria

        Key Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Histologically or cytologically documented locally advanced unresectable or metastatic
             non-squamous NSCLC

          -  No prior systemic treatment for metastatic non-squamous NSCLC

          -  Known tumor programmed death-ligand 1 (PD-L1) status

          -  Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors,
             version 1.1 (RECIST v1.1)

          -  Life expectancy >= 12 weeks

          -  Adequate hematologic and end-organ function

          -  Negative human immunodeficiency virus (HIV) test at screening

          -  Serology test negative for active hepatitis B virus or active hepatitis C virus at
             screening

        Key Exclusion Criteria:

          -  Mutations in epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma
             kinase (ALK) fusion oncogene

          -  Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC

          -  Symptomatic, untreated, or actively progressing central nervous system (CNS)
             metastases

          -  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

          -  History of malignancy other than NSCLC within 5 years prior to randomization, with the
             exception of malignancies with a negligible risk of metastasis or death

          -  Severe infection within 4 weeks prior to initiation of study treatment

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and
             anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents 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

          -  Women who are pregnant, or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Investigator-Assessed Confirmed Objective Response Rate (ORR)
Time Frame:From randomization up to 5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:From randomization to death from any cause (up to 5 years)
Safety Issue:
Description:
Measure:Investigator-Assessed Duration of Response (DOR)
Time Frame:From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 5 years)
Safety Issue:
Description:
Measure:Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30
Time Frame:From randomization until the first confirmed clinically meaningful deterioration (up to 5 years)
Safety Issue:
Description:TTCD using EORTC Quality-of-Life Questionnaire Core 30 (QLQ-C30) is an initial 10-point decrease in GHS and physical functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea/vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
Measure:TTCD in Participant-Reported Lung Cancer Symptoms for Cough, Dyspnea, and Chest Pain, as Measured by EORTC QLQ-LC13
Time Frame:From randomization until the first confirmed clinically meaningful deterioration (up to 5 years)
Safety Issue:
Description:TTCD using EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13) is an initial 10-point increase in symptom score from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-LC13 consists of 13 lung cancer specific items and includes 11 disease-specific scales/items (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication). Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates worsening of symptoms.
Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Participants' Response to Side Effects of Treatment as Assessed by EORTC IL46
Time Frame:Up to 5 years
Safety Issue:
Description:EORTC Item List 46 (IL46) is a validated single-item question that assesses overall side effect impact. Each item is scored on a 4-point scale of 1=Not at all to 4=Very much. Scores will be linearly transformed to a score range of 0 to 100. Higher score indicates a worse outcome.
Measure:Serum Concentration of Tiragolumab
Time Frame:Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to 5 years)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 h postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at TD visit (up to 5 years)
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Time Frame:Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to 5 years)
Safety Issue:
Description:
Measure:Percentage of Participants With ADAs to Atezolizumab
Time Frame:Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to 5 years)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 5, 2020