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/NCT03005782




Registration number
NCT03005782
Ethics application status
Date submitted
18/11/2016
Date registered
29/12/2016
Date last updated
30/04/2020

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
Treatment: Drugs - REGN3767
Treatment: Drugs - cemiplimab

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


Treatment: Drugs: REGN3767


Treatment: Drugs: cemiplimab


Intervention code [1] 0 0
Treatment: Drugs
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
Gender
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
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)
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Peter Maccallum Cancer Centre (PMCC) - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 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
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Rhode Island
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
Ireland
State/province [22] 0 0
Dublin
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Europe
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Regeneron Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives in the dose escalation phase are to evaluate safety and
pharmacokinetics (PK) in order to determine the selected dose level(s) for expansion of
REGN3767 as monotherapy and in combination with cemiplimab in patients with advanced
malignancies, including lymphoma.

The primary objectives in the dose expansion phase are to assess preliminary anti-tumor
activity of REGN3767 alone and in combination with cemiplimab (separately by cohort) as
measured by objective response rate (ORR).
Trial website
https://clinicaltrials.gov/show/NCT03005782
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
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
clinicaltrials@regeneron.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03005782