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Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers

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ClinicalTrials.gov Identifier: NCT03005782
Recruitment Status : Recruiting
First Posted : December 29, 2016
Last Update Posted : June 18, 2018
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 18, 2016
First Posted Date  ICMJE December 29, 2016
Last Update Posted Date June 18, 2018
Actual Study Start Date  ICMJE November 7, 2016
Estimated Primary Completion Date September 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Rate of dose limiting toxicities (Dose Escalation Phase) [ Time Frame: Baseline to 28 days ]
  • Rate of adverse events (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Rate of serious adverse events (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Occurrence of death (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • 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) [ Time Frame: Baseline to 51 weeks ]
  • AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • AUC computed from time zero to the time of the last positive concentration [AUClast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to week 51 ]
  • Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • 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) [ Time Frame: Baseline to 51 weeks ]
  • Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase) [ Time Frame: Baseline to 51 weeks ]
  • Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 23, 2016)
  • Rate of dose limiting toxicities (Dose Escalation Phase) [ Time Frame: Baseline to 28 days ]
  • Rate of adverse events (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Rate of serious adverse events (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Occurrence of death (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Maximum Plasma Concentration [Cmax] (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Area Under the Curve [AUC] (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase) [ Time Frame: Baseline to 51 weeks ]
  • Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
Change History Complete list of historical versions of study NCT03005782 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Best overall response based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Best overall response based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Duration of response based on RECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Duration of response based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Duration of response based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Disease control rate based on RECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Disease control rate based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Disease control rate based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on RECIST (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on irRECIST (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of adverse events (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of serious adverse events (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of death (Dose Expansion Phase) [ Time Frame: From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months ]
  • Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2016)
  • Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Best overall response based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Best overall response based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Duration of response based on RECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Duration of response based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Duration of response based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to week 51 ]
  • Disease control rate based on RECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Disease control rate based on irRECIST criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Disease control rate based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on RECIST (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on irRECIST (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Progression free survival based on Lugano criteria (Dose Escalation Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of adverse events (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of serious adverse events (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of death (Dose Expansion Phase) [ Time Frame: From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months ]
  • Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Maximum Plasma Concentration [Cmax] (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Area Under the Curve [AUC] (Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
  • Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase) [ Time Frame: Baseline to 51 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers
Official Title  ICMJE 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
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 REGN2810 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 REGN2810 (separately by cohort) as measured by objective response rate (ORR).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignancies
Intervention  ICMJE
  • Drug: REGN3767
  • Drug: REGN2810
Study Arms  ICMJE
  • 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.
    Intervention: Drug: REGN3767
  • Experimental: Combination Therapy (REGN3767+REGN2810)
    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
    Interventions:
    • Drug: REGN3767
    • Drug: REGN2810
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 13, 2018)
546
Original Estimated Enrollment  ICMJE
 (submitted: December 23, 2016)
283
Estimated Study Completion Date  ICMJE March 29, 2022
Estimated Primary Completion Date September 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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 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
  • Documented allergic or acute hypersensitivity reaction attributed to antibody treatments

Note: Other protocol defined Inclusion / Exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Korea, Republic of,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03005782
Other Study ID Numbers  ICMJE R3767-ONC-1613
2016-002789-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Regeneron Pharmaceuticals
Study Sponsor  ICMJE Regeneron Pharmaceuticals
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP