We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Pharmacokinetics of REGN2810 (Cemiplimab) Anti-programmed Death-ligand 1 (Anti-PD-1) in Japanese Adult Patients With Advanced Malignancies

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03233139
Recruitment Status : Recruiting
First Posted : July 28, 2017
Last Update Posted : September 1, 2022
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE July 25, 2017
First Posted Date  ICMJE July 28, 2017
Last Update Posted Date September 1, 2022
Actual Study Start Date  ICMJE June 21, 2017
Estimated Primary Completion Date May 24, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2022)
  • Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with cemiplimab [ Time Frame: Up to 136 weeks ]
  • PK of cemiplimab: Cmax [ Time Frame: Up to 136 weeks ]
    Peak serum concentration
  • PK of cemiplimab: tmax [ Time Frame: Up to 136 weeks ]
    Time to Cmax
  • PK of cemiplimab: Ctrough [ Time Frame: Up to 136 weeks ]
    Drug concentration in serum at the end of a dosing interval
  • PK of cemiplimab: Area under the drug concentration-time curve in serum (AUC3w) [ Time Frame: Up to 136 weeks ]
    AUC over a 3-week dosing interval
  • PK of cemiplimab: t½ estimated over a 3-week dosing interval [ Time Frame: Up to 136 weeks ]
    Observed terminal half-life
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
  • Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with REGN2810 [ Time Frame: Up to 82 weeks ]
  • PK of REGN2810: Cmax [ Time Frame: Up to 82 weeks ]
    Peak serum concentration
  • PK of REGN2810: tmax [ Time Frame: Up to 82 weeks ]
    Time to Cmax
  • PK of REGN2810: Ctrough [ Time Frame: Up to 82 weeks ]
    Drug concentration in serum at the end of a dosing interval
  • PK of REGN2810: Area under the drug concentration-time curve in serum AUC3w [ Time Frame: Up to 82 weeks ]
    AUC over a 3-week dosing interval
  • PK of REGN2810: t½ estimated over a 3-week dosing interval [ Time Frame: Up to 82 weeks ]
    Observed terminal half-life
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2021)
  • Immunogenicity against cemiplimab [ Time Frame: Up to 136 weeks ]
    Evaluate the immunogenicity of cemiplimab after single-dose administration
  • Objective Response Rate (ORR) [ Time Frame: Up to 135 weeks ]
    As assessed by an Independent Review Committee (IRC) using RECIST 1.1 (Eisenhauer 2009) in Part 2, Cohorts A and C
  • Duration of Response (DOR) [ Time Frame: Up to 136 weeks ]
    As assessed by an IRC (per RECIST1.1) in Part 2, Cohorts A and C
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
Immunogenicity against REGN2810 [ Time Frame: Up to 82 weeks ]
Evaluate the immunogenicity of REGN2810 after single-dose administration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacokinetics of REGN2810 (Cemiplimab) Anti-programmed Death-ligand 1 (Anti-PD-1) in Japanese Adult Patients With Advanced Malignancies
Official Title  ICMJE A Phase 1 Study to Investigate the Safety and Pharmacokinetics of REGN2810 (Anti-PD-1) in Japanese Patients With Advanced Malignancies
Brief Summary

The primary objective of the study is to assess the safety, tolerability, and Pharmacokinetics (PK) of cemiplimab in Japanese patients with advanced malignancies.

The secondary objectives are:

  • To assess the immunogenicity of cemiplimab
  • To evaluate tumor response (objective response rate [ORR] and duration of response [DOR] to cemiplimab monotherapy as first line treatment of Japanese patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand 1 (PD-L1) in ≥50% of tumor cells (PD-L1^hi). (Part 2, Cohort A)
  • To evaluate tumor response ORR and DOR to cemiplimab plus chemotherapy as first line treatment of Japanese patients with advanced squamous or non-squamous NSCLC whose tumors express any level of PD-L1 (PD-L1^any). (Part 2, Cohort C)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Malignancies
Intervention  ICMJE
  • Drug: Cemiplimab
    Patients will be administered cemiplimab as per protocol. For Cohort A Only, patients with confirmed progressive disease may opt to receive up to 4 cycles of platinum doublet chemotherapy in addition to cemiplimab per investigator's judgement.
    Other Names:
    • REGN2810
    • Libtayo
  • Drug: Ipilimumab
    To be administered per protocol
  • Drug: Platinum-doublet chemotherapy
    To be administered per protocol
  • Drug: Gemcitabine
    To be administered per protocol
    Other Name: Gemzar
  • Drug: Pemetrexed
    To be administered per protocol
    Other Name: Alimta
  • Drug: Paclitaxel
    To be administered per protocol
    Other Name: Taxol
Study Arms  ICMJE
  • Experimental: Cemiplimab
    Part 1
    Intervention: Drug: Cemiplimab
  • Experimental: Cohort A
    Part 2
    Intervention: Drug: Cemiplimab
  • Experimental: Cohort B
    Part 2
    Interventions:
    • Drug: Cemiplimab
    • Drug: Ipilimumab
    • Drug: Platinum-doublet chemotherapy
    • Drug: Gemcitabine
    • Drug: Pemetrexed
    • Drug: Paclitaxel
  • Experimental: Cohort C
    Part 2
    Interventions:
    • Drug: Cemiplimab
    • Drug: Platinum-doublet chemotherapy
    • Drug: Pemetrexed
    • Drug: Paclitaxel
Publications * Kitano S, Shimizu T, Koyama T, Ebata T, Iwasa S, Kondo S, Shimomura A, Fujiwara Y, Yamamoto N, Paccaly A, Li S, Rietschel P, Sims T. Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies. Cancer Chemother Pharmacol. 2021 Jan;87(1):53-64. doi: 10.1007/s00280-020-04161-6. Epub 2020 Nov 4.

*   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: November 4, 2021)
117
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2017)
6
Estimated Study Completion Date  ICMJE May 24, 2026
Estimated Primary Completion Date May 24, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Disease types under study:

    • Part 1: Histologically or cytologically confirmed diagnosis of malignancy with no alternative standard-of-care therapeutic option
    • Part 2: Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC or stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC.
    • Patients in Part 2 NSCLC cohorts must have available archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated.
  2. ECOG (Eastern Cooperative Oncology Group) PS (Performance status) ≤1 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature [eg, light house work or office work]). Note: Patients with ECOG PS >1 are ineligible.
  3. Patients must have been born in Japan, and their biological parents and grandparents must all have been of Japanese origin
  4. Willing and able to comply with clinic visits and study-related procedures

Key Exclusion Criteria:

  1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires treatment with systemic immunosuppressive treatments, which may suggest risk for Immune-related adverse event (irAE)s. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement or psoriasis that does not require systemic treatment.
  2. Untreated brain metastasis (es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable, there is no evidence of new or enlarging brain metastases, and the patient does not require any systemic corticosteroids for management of brain metastases within 4 weeks prior to the first dose of cemiplimab.
  3. Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab.
  4. Any positive test (ribonucleic acid (RNA) or Deoxyribonucleic acid (DNA) by polymerase chain reaction) for hepatitis B, hepatitis C, or human immunodeficiency virus indicating uncontrolled active or chronic infection.
  5. History of pneumonitis or interstitial lung disease
  6. Surgery within 1 month of first dose and radiation therapy within 2 weeks of first dose
  7. Completed palliative radiation therapy within the prior 2 weeks or has not recovered from any medically significant radiation-related Adverse Event (AE)
  8. Patients that have never smoked, defined as smoking ≤100 cigarettes in a lifetime (Part 2)
  9. Patients with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS1 fusions (Part 2)

Note: Other protocol defined inclusion/exclusion criteria apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 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 Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03233139
Other Study ID Numbers  ICMJE R2810-ONC-1622
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Regeneron Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Regeneron Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date August 2022

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