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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03005782




Registration number
NCT03005782
Ethics application status
Date submitted
18/11/2016
Date registered
29/12/2016
Date last updated
1/05/2024

Titles & IDs
Public title
Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers
Scientific title
A Phase 1, Open-Label, Dose-Escalation and Cohort Expansion First-in-Human Study of the Safety, Tolerability, Activity and Pharmacokinetics of REGN3767 (Anti-LAG-3 mAb) Administered Alone or in Combination With REGN2810 (Anti-PD-1 mAb) in Patients With Advanced Malignancies
Secondary ID [1] 0 0
2016-002789-30
Secondary ID [2] 0 0
R3767-ONC-1613
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignancies 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Monotherapy (REGN3767) - Group A will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition 1 tumor-specific cohort will be treated at the recommended phase 2 dose (RP2D) during dose expansion.

Experimental: Combination Therapy (REGN3767+cemiplimab) - Group B will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition, 9 tumor-specific cohorts will be treated at the RP2D during dose expansion
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of dose limiting toxicities (Dose Escalation Phase)
Timepoint [1] 0 0
Baseline to 28 days
Primary outcome [2] 0 0
Rate of adverse events (Dose Escalation Phase)
Timepoint [2] 0 0
Baseline to 51 weeks
Primary outcome [3] 0 0
Rate of serious adverse events (Dose Escalation Phase)
Timepoint [3] 0 0
Baseline to 51 weeks
Primary outcome [4] 0 0
Occurrence of death (Dose Escalation Phase)
Timepoint [4] 0 0
Baseline to 51 weeks
Primary outcome [5] 0 0
Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase)
Timepoint [5] 0 0
Baseline to 51 weeks
Primary outcome [6] 0 0
Area under the curve (AUC) computed from time zero to the time of the last concentration [AUCall] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [6] 0 0
Baseline to 51 weeks
Primary outcome [7] 0 0
AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [7] 0 0
Baseline to 51 weeks
Primary outcome [8] 0 0
AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [8] 0 0
Baseline to 51 weeks
Primary outcome [9] 0 0
AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [9] 0 0
Baseline to 51 weeks
Primary outcome [10] 0 0
AUC computed from time zero to the time of the last positive concentration [AUClast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [10] 0 0
Baseline to 51 weeks
Primary outcome [11] 0 0
AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [11] 0 0
Baseline to 51 weeks
Primary outcome [12] 0 0
Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [12] 0 0
Baseline to 51 weeks
Primary outcome [13] 0 0
Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [13] 0 0
Baseline to week 51
Primary outcome [14] 0 0
Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [14] 0 0
Baseline to 51 weeks
Primary outcome [15] 0 0
Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [15] 0 0
Baseline to 51 weeks
Primary outcome [16] 0 0
Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)
Timepoint [16] 0 0
Baseline to 51 weeks
Primary outcome [17] 0 0
Mean residence time when the drug concentration profile is based on values up to and including the last positive concentration [MRTlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [17] 0 0
Baseline to 51 weeks
Primary outcome [18] 0 0
Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [18] 0 0
Baseline to 51 weeks
Primary outcome [19] 0 0
t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [19] 0 0
Baseline to 51 weeks
Primary outcome [20] 0 0
Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [20] 0 0
Baseline to 51 weeks
Primary outcome [21] 0 0
Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [21] 0 0
Baseline to 51 weeks
Primary outcome [22] 0 0
Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [22] 0 0
Baseline to 51 weeks
Primary outcome [23] 0 0
Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
Timepoint [23] 0 0
Baseline to 51 weeks
Primary outcome [24] 0 0
Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)
Timepoint [24] 0 0
Baseline to 51 weeks
Primary outcome [25] 0 0
Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)
Timepoint [25] 0 0
Baseline to 51 weeks
Secondary outcome [1] 0 0
Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)
Timepoint [1] 0 0
Baseline to week 51
Secondary outcome [2] 0 0
Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)
Timepoint [2] 0 0
Baseline to week 51
Secondary outcome [3] 0 0
Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)
Timepoint [3] 0 0
Baseline to 51 weeks
Secondary outcome [4] 0 0
Best overall response based on irRECIST criteria (Dose Escalation Phase)
Timepoint [4] 0 0
Baseline to 51 weeks
Secondary outcome [5] 0 0
Best overall response based on Lugano criteria (Dose Escalation Phase)
Timepoint [5] 0 0
Baseline to 51 weeks
Secondary outcome [6] 0 0
Duration of response based on RECIST criteria (Dose Escalation Phase)
Timepoint [6] 0 0
Baseline to week 51
Secondary outcome [7] 0 0
Duration of response based on irRECIST criteria (Dose Escalation Phase)
Timepoint [7] 0 0
Baseline to week 51
Secondary outcome [8] 0 0
Duration of response based on Lugano criteria (Dose Escalation Phase)
Timepoint [8] 0 0
Baseline to week 51
Secondary outcome [9] 0 0
Disease control rate based on RECIST criteria (Dose Escalation Phase)
Timepoint [9] 0 0
Baseline to 51 weeks
Secondary outcome [10] 0 0
Disease control rate based on irRECIST criteria (Dose Escalation Phase)
Timepoint [10] 0 0
Baseline to 51 weeks
Secondary outcome [11] 0 0
Disease control rate based on Lugano criteria (Dose Escalation Phase)
Timepoint [11] 0 0
Baseline to 51 weeks
Secondary outcome [12] 0 0
Progression free survival based on RECIST (Dose Escalation Phase)
Timepoint [12] 0 0
Baseline to 51 weeks
Secondary outcome [13] 0 0
Progression free survival based on irRECIST (Dose Escalation Phase)
Timepoint [13] 0 0
Baseline to 51 weeks
Secondary outcome [14] 0 0
Progression free survival based on Lugano criteria (Dose Escalation Phase)
Timepoint [14] 0 0
Baseline to 51 weeks
Secondary outcome [15] 0 0
Incidence of adverse events (Dose Expansion Phase)
Timepoint [15] 0 0
Baseline to 51 weeks
Secondary outcome [16] 0 0
Incidence of serious adverse events (Dose Expansion Phase)
Timepoint [16] 0 0
Baseline to 51 weeks
Secondary outcome [17] 0 0
Incidence of death (Dose Expansion Phase)
Timepoint [17] 0 0
From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months
Secondary outcome [18] 0 0
Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase)
Timepoint [18] 0 0
Baseline to 51 weeks
Secondary outcome [19] 0 0
Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)
Timepoint [19] 0 0
Baseline to 51 weeks

Eligibility
Key inclusion criteria
Key

* Dose escalation cohorts: Patients with histologically or cytologically confirmed diagnosis of malignancy (including lymphoma) with demonstrated progression of a tumor for whom there is no available therapy likely to convey clinical benefit AND who have not been previously treated with a PD-1/PD-L1 inhibitor. These patients do not require measurable disease
* Dose expansion cohorts: Patients with histologically or cytologically confirmed diagnosis of 1 of specified tumors with measurable disease per RECIST 1.1 or Lugano criteria. Some patients may have been previously treated with a PD-1 or PD-L1 inhibitor
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Adequate organ and bone marrow function

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any LAG-3 targeting biologic or small molecule
* Radiation therapy within 2 weeks prior to randomization and not recovered to baseline from any AE due to radiation
* Untreated or active central nervous system metastases - Ongoing or recent (within 5 years) evidence of significant autoimmune disease
* Corticosteroid therapy (>10 mg prednisone/day or equivalent) within 1 week prior to the first dose of study drug
* Myocardial infarction within 6 months

Note: Other protocol defined Inclusion / Exclusion criteria apply

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/04/2024
Sample size
Target
Accrual to date
Final
333
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH) - Perth
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [3] 0 0
Peter Maccallum Cancer Centre (PMCC) - Melbourne
Recruitment postcode(s) [1] 0 0
06009 - Perth
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New Mexico
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Rhode Island
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Ireland
State/province [21] 0 0
Dublin
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Europe
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03005782