The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02794571




Registration number
NCT02794571
Ethics application status
Date submitted
6/06/2016
Date registered
9/06/2016
Date last updated
15/07/2019

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2016-000944-33
Secondary ID [2] 0 0
GO30103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - MTIG7192A

Experimental: Phase Ia Dose-Escalation Stage: MTIG7192A - Cohorts of at least 3 participants each will be treated with escalating doses of MTIG7192A to determine the MTD or maximum administered dose (MAD).

Experimental: Phase Ia Expansion Stage: MTIG7192A - Approximately 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.

Experimental: Phase Ib Dose-Escalation Stage: MTIG7192A+Atezolizumab - Cohorts 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.

Experimental: Phase Ib Expansion Stage: MTIG7192A+Atezolizumab - At 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.


Treatment: Drugs: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle in combination with MTIG7192A. Combination treatment may continue until disease progression or loss of clinical benefit.

Treatment: Drugs: MTIG7192A
Several dose levels will be evaluated for MTIG7192A administered as a single agent and in combination with atezolizumab. MTIG7192A will be given via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent MTIG7192A may receive combination treatment with MTIG7192A plus atezolizumab. Combination treatment may continue until disease progression or loss of clinical benefit.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
From Baseline to the end of Cycle 1 (up to 21 days)
Primary outcome [2] 0 0
Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
Timepoint [2] 0 0
From Baseline up to 90 days after last dose of study treatment or until initiation of another systemic anti-cancer therapy (up to approximately 3 years)
Primary outcome [3] 0 0
Number of Cycles with MTIG7192A
Timepoint [3] 0 0
From Baseline to last dose (up to approximately 3 years)
Primary outcome [4] 0 0
Dosage in Milligrams (mg) of MTIG7192A
Timepoint [4] 0 0
From Baseline to last dose (up to approximately 3 years)
Primary outcome [5] 0 0
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to MTIG7192A
Timepoint [5] 0 0
From Baseline to last ATA measurement; drawn pre-dose (0 hours [h]) Day 1 of Cycles 1-4, 8 (cycle = 21 days); then every eight cycles (Q8C) until/at discontinuation (DC) (up to 3 years); every 30 days thereafter up to 120 days (up to 3 years overall)
Primary outcome [6] 0 0
Percentage of Participants with ATAs to Atezolizumab
Timepoint [6] 0 0
From Baseline to last ATA measurement; drawn pre-dose (0 h) Day 1 of Cycles 1-4, 8 (cycle = 21 days); then Q8C until/at DC (up to 3 years); every 30 days thereafter up to 120 days (up to 3 years overall)
Secondary outcome [1] 0 0
Area Under the Concentration-Time Curve (AUC) of MTIG7192A during Phase Ia Dose-Escalation Stage
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
AUC of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Maximum Serum Concentration (Cmax) of MTIG7192A during Phase Ia Dose-Escalation Stage
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
Cmax of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Minimum Serum Concentration (Cmin) of MTIG7192A during Phase Ia Dose-Escalation Stage
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Cmin of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Clearance (CL) of MTIG7192A during Phase Ia Dose-Escalation Stage
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
CL of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Volume of Distribution at Steady State (Vss) of MTIG7192A during Phase Ia Dose-Escalation Stage
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Vss of MTIG7192A during Phase Ia Expansion Stage and Phase Ib Stages
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Progression-Free Survival (PFS) According to RECIST Version 1.1
Timepoint [11] 0 0
From Baseline until disease progression (up to 3 years)
Secondary outcome [12] 0 0
Cmax of Atezolizumab during Phase Ib Dose-Escalation Stage
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Cmax of Atezolizumab during Phase Ib Expansion Stage
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Cmin of Atezolizumab during Phase Ib Stages
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [15] 0 0
From Baseline until disease progression (up to 3 years)
Secondary outcome [16] 0 0
Duration of Objective Response (DOR) According to RECIST Version 1.1
Timepoint [16] 0 0
From Baseline until disease progression (up to 3 years)
Secondary outcome [17] 0 0
Maximum Tolerated Dose (MTD) in mg of MTIG7192A as a Single Agent and in Combination with Atezolizumab
Timepoint [17] 0 0
From Baseline to the end of Cycle 1 (up to 21 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
France
State/province [10] 0 0
Bordeaux
Country [11] 0 0
France
State/province [11] 0 0
Lyon
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Toulouse
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Spain
State/province [16] 0 0
Barcelona
Country [17] 0 0
Spain
State/province [17] 0 0
Navarra
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Spain
State/province [19] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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 website
https://clinicaltrials.gov/show/NCT02794571
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications