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

A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Cemiplimab (Anti-PD-1) and Other Agents in Japanese Patients With Advanced Malignancies

Part 2 Cohorts A and C This study is being conducted to test the safety and pharmacokinetics of cemiplimab in patients with lung cancer. The study is also being conducted to test if cemiplimab, alone or in combination, can reduce the size of your tumor by helping the immune system destroy the tumor.

Part 2 Cohorts D and E This study is being conducted to test the safety and pharmacokinetics of fianlimab and cemiplimab in patients with lung cancer. The study is also being conducted to test if fianlimab and cemiplimab, with or without chemotherapy, can reduce the size of your tumor by helping the immune system destroy the tumor.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: Cemiplimab; Drug: Ipilimumab; Drug: Platinum-doublet chemotherapy; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Fianlimab

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Japan
  • Gunma, Japan, 373-8550
    • Recruiting
    • Gunma Prefectural Cancer Center
  • Hiroshima, Japan, 730-8518
    • Recruiting
    • Hiroshima City Hiroshima Citizens Hospital
  • Nagasaki, Japan, 852-8501
    • Recruiting
    • Nagasaki University Hospital
  • Osaka, Japan, 545-8586
    • Recruiting
    • Osaka City University Hospital
  • Osaka, Japan, 541-8567
    • Recruiting
    • Osaka International Cancer Center
  • Tokushima, Japan, 770-8503
    • Recruiting
    • Tokushima University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • Recruiting
      • Nagoya Medical Center
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Recruiting
      • Kurume University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Recruiting
      • Kobe City Medical Center General Hospital
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Recruiting
      • Kanazawa University Hospital
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Recruiting
      • Kitasato University Hospital
    • Yokohama, Kanagawa, Japan, 236-0051
      • Recruiting
      • Kanagawa Cardiovascular and Respiratory Center
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa cancer center
  • Nagasaki
    • Sasebo, Nagasaki, Japan, 857-8511
      • Recruiting
      • Sasebo City General Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8515
      • Recruiting
      • Kurashiki Central Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Recruiting
      • Kansai Medical University Hospital
    • Sakai, Osaka, Japan, 591-8555
      • Recruiting
      • Kinki-chuo Chest Medical Center
    • Takatsuki, Osaka, Japan, 569-8686
      • Recruiting
      • Osaka Medical College Hospital
  • Saitama
    • Kita Adachi, Saitama, Japan, 362-0806
      • Recruiting
      • Saitama Cancer Center
  • Tokyo
    • Cho-Ku, Tokyo, Japan, 104-0055
      • Active, not recruiting
      • National Cancer Center Hospital
    • Shinjuku, Tokyo, Japan, 160-0023
      • Withdrawn
      • Tokyo Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 housework 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
5. For Part 2, Cohorts D and E: Available tissue for retrospective testing using assay performed by a central laboratory, as specified in the study manual.

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-mediated adverse event (imAE)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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cemiplimab; Part 1	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
Experimental: Cohort A; Part 2	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
Experimental: Cohort B; Part 2	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 Names: Gemzar; Drug: Pemetrexed; To be administered per protocol; Other Names: Alimta; Drug: Paclitaxel; To be administered per protocol; Other Names: Taxol
Experimental: Cohort C; Part 2	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: Platinum-doublet chemotherapy; To be administered per protocol; Drug: Pemetrexed; To be administered per protocol; Other Names: Alimta; Drug: Paclitaxel; To be administered per protocol; Other Names: Taxol
Experimental: Cohort D; Part 2	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: Fianlimab; To be administered per protocol
Experimental: Cohort E; Part 2	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: Platinum-doublet chemotherapy; To be administered per protocol; Drug: Pemetrexed; To be administered per protocol; Other Names: Alimta; Drug: Paclitaxel; To be administered per protocol; Other Names: Taxol; Drug: Fianlimab; To be administered per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of cemiplimab: Cmax	Peak serum concentration	Up to 136 weeks
PK of cemiplimab: tmax	Time to Cmax	Up to 136 weeks
PK of cemiplimab: Ctrough	Drug concentration in serum at the end of a dosing interval	Up to 136 weeks
PK of cemiplimab: Area under the drug concentration-time curve in serum (AUC3w)	AUC over a 3-week dosing interval	Up to 136 weeks
PK of cemiplimab: t½ estimated over a 3-week dosing interval	Observed terminal half-life	Up to 136 weeks
Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with cemiplimab as monotherapy		Up to 136 weeks
Incidence and severity of TEAEs in patients treated with cemiplimab in combination with other agents		Up to 136 weeks
Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab without chemotherapy		Up to 136 weeks
Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab with chemotherapy		Up to 136 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	As assessed by an Independent Review Committee (IRC) using RECIST 1.1 (Eisenhauer 2009) in Part 2, Cohorts A and C	Up to 135 weeks
Duration of Response (DOR)	As assessed by an IRC (per RECIST1.1) in Part 2, Cohorts A and C	Up to 136 weeks
Immunogenicity against cemiplimab and fianlimab	Evaluate the immunogenicity of cemiplimab and fianlimab after single-dose administration	Up to 136 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2017
• Primary Completion (Estimated): December 22, 2027
• Study Completion (Estimated): March 27, 2030

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (Actual): July 28, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Japanese patients
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Paclitaxel; Pemetrexed; Ipilimumab; Cemiplimab; Gemcitabine
• Other Study ID Numbers: R2810-ONC-1622

Drug and device information, study documents

• 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