Clinical Trials /

Safety and Pharmacokinetics (PK) of Escalating Doses of MTIG7192A as a Single Agent and in Combination With Atezolizumab With and Without Chemotherapy in Locally Advanced or Metastatic Tumors

NCT02794571

Description:

This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of MTIG7192A alone or in combination with atezolizumab administered with and without chemotherapy in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Pharmacokinetics (PK) of Escalating Doses of MTIG7192A as a Single Agent and in Combination With Atezolizumab in Locally Advanced or Metastatic Tumors
  • Official Title: A Phase Ia/Ib Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MTIG7192A as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Tumors

Clinical Trial IDs

  • ORG STUDY ID: GO30103
  • SECONDARY ID: 2016-000944-33
  • NCT ID: NCT02794571

Conditions

  • Advanced/Metastatic Tumors

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280APhase Ib Dose-Escalation Stage: MTIG7192A+Atezolizumab
MTIG7192ARO7092284, tiragolumabPhase Ia Dose-Escalation Stage: MTIG7192A

Purpose

This first-in-human open-label, multicenter, dose-escalation study is designed to evaluate the safety, tolerability, and PK of MTIG7192A alone or in combination with atezolizumab in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.

Trial Arms

NameTypeDescriptionInterventions
Phase Ia Dose-Escalation Stage: MTIG7192AExperimentalCohorts of at least 3 participants each will be treated with escalating doses of MTIG7192A to determine the MTD or maximum administered dose (MAD).
  • MTIG7192A
Phase Ia Expansion Stage: MTIG7192AExperimentalApproximately 20 to 40 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of MTIG7192A in different cancer types.
  • MTIG7192A
Phase Ib Dose-Escalation Stage: MTIG7192A+AtezolizumabExperimentalCohorts of at least 3 participants each will be treated with escalating doses of MTIG7192A in combination with a fixed dose of atezolizumab to determine the MTD or MAD.
  • Atezolizumab
  • MTIG7192A
Phase Ib Expansion Stage: MTIG7192A+AtezolizumabExperimentalAt least approximately 160 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of MTIG7192A in combination with atezolizumab in different cancer types.
  • Atezolizumab
  • MTIG7192A

Eligibility Criteria

        Inclusion Criteria:

          -  Adults 18 years of age or older

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy at least 12 weeks

          -  Adequate hematologic and end organ function

          -  Histologic documentation of locally advanced, recurrent, or metastatic incurable
             malignancy that has progressed after at least one available standard therapy; or for
             which standard therapy has proven ineffective, intolerable, or considered
             inappropriate; or for which a clinical trial of an investigational agent is a
             recognized standard of care

          -  Confirmed availability of representative tumor specimens

          -  Measurable disease according to RECIST Version 1.1

        Exclusion Criteria:

          -  Any anti-cancer therapy, whether investigational or approved, including chemotherapy,
             hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study
             treatment

          -  Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1

          -  Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases

          -  Leptomeningeal disease

          -  History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or
             evidence of active pneumonitis on Screening chest computed tomograph (CT) scan

          -  History of autoimmune disease

          -  Positive human immunodeficiency virus (HIV) test

          -  Active hepatitis B or C, or tuberculosis

          -  Severe infection within 4 weeks prior to randomization

          -  Prior allogeneic bone marrow or solid organ transplant

          -  Significant cardiovascular disease

          -  Known clinically significant liver disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:From Baseline to the end of Cycle 1 (up to 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area Under the Concentration-Time Curve (AUC) of MTIG7192A during Phase Ia Dose-Escalation Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-7 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:AUC of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-4 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Maximum Serum Concentration (Cmax) of MTIG7192A during Phase Ia Dose-Escalation Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-7 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Cmax of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-4 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) of MTIG7192A during Phase Ia Dose-Escalation Stage
Time Frame:Pre-dose (0 h) Day 1 of Cycles 1-8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Cmin of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Time Frame:Pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Clearance (CL) of MTIG7192A during Phase Ia Dose-Escalation Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-7 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:CL of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-4 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of MTIG7192A during Phase Ia Dose-Escalation Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-7 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Vss of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-4 (cycle = 21 days); post-dose (24 h) Day 2 of Cycle 1; on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) According to RECIST Version 1.1
Time Frame:From Baseline until disease progression (up to 3 years)
Safety Issue:
Description:
Measure:Cmax of Atezolizumab during Phase Ib Dose-Escalation Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1-4 (cycle = 21 days); on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Cmax of Atezolizumab during Phase Ib Expansion Stage
Time Frame:Post-dose (0.5 h) Day 1 of Cycles 1, 4 (cycle = 21 days); on Days 8, 15 of Cycle 1; pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Cmin of Atezolizumab during Phase Ib Stages
Time Frame:Pre-dose (0 h) Day 1 of Cycles 1-4, 8; then Q8C until/at DC (up to 3 years); every 30 days up to 120 days (up to 3 years overall)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:From Baseline until disease progression (up to 3 years)
Safety Issue:
Description:
Measure:Duration of Objective Response (DOR) According to RECIST Version 1.1
Time Frame:From Baseline until disease progression (up to 3 years)
Safety Issue:
Description:
Measure:Maximum Tolerated Dose (MTD) in mg of MTIG7192A as a Single Agent and in Combination with Atezolizumab
Time Frame:From Baseline to the end of Cycle 1 (up to 21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

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