Safety and Pharmacokinetics of Cemiplimab Anti-programmed Death-ligand 1 (Anti-PD-1) and Other Agents in Japanese Adult Patients With Advanced Malignancies
- Conditions
- Advanced Malignancies
- Interventions
- Drug: Platinum-doublet chemotherapy
- Registration Number
- NCT03233139
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 146
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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.
-
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.
-
Patients must have been born in Japan, and their biological parents and grandparents must all have been of Japanese origin
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Willing and able to comply with clinic visits and study-related procedures
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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
- 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.
- 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.
- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab.
- 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.
- History of pneumonitis or interstitial lung disease
- Surgery within 1 month of first dose and radiation therapy within 2 weeks of first dose
- Completed palliative radiation therapy within the prior 2 weeks or has not recovered from any medically significant radiation-related Adverse Event (AE)
- Patients that have never smoked, defined as smoking ≤100 cigarettes in a lifetime (Part 2)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A Cemiplimab Part 2 Cohort C Cemiplimab Part 2 Cohort B Ipilimumab Part 2 Cohort B Platinum-doublet chemotherapy Part 2 Cohort B Cemiplimab Part 2 Cohort B Gemcitabine Part 2 Cohort B Pemetrexed Part 2 Cohort C Platinum-doublet chemotherapy Part 2 Cohort C Pemetrexed Part 2 Cohort C Paclitaxel Part 2 Cohort D Cemiplimab Part 2 Cohort D Fianlimab Part 2 Cohort E Platinum-doublet chemotherapy Part 2 Cohort E Paclitaxel Part 2 Cohort E Fianlimab Part 2 Cemiplimab Cemiplimab Part 1 Cohort B Paclitaxel Part 2 Cohort E Cemiplimab Part 2 Cohort E Pemetrexed Part 2
- Primary Outcome Measures
Name Time Method 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 PK of cemiplimab: tmax Up to 136 weeks Time to Cmax
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 fianlimab in combination with cemiplimab with chemotherapy Up to 136 weeks PK of cemiplimab: Cmax Up to 136 weeks Peak serum concentration
PK of cemiplimab: Ctrough 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) Up to 136 weeks AUC over a 3-week dosing interval
PK of cemiplimab: t½ estimated over a 3-week dosing interval Up to 136 weeks Observed terminal half-life
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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) Up to 136 weeks As assessed by an IRC (per RECIST1.1) in Part 2, Cohorts A and C
Immunogenicity against cemiplimab and fianlimab Up to 136 weeks Evaluate the immunogenicity of cemiplimab and fianlimab after single-dose administration
Trial Locations
- Locations (20)
National Cancer Center Hospital - Tsukiji Campus
🇯🇵Chuo ku, Tokyo, Japan
Saitama Cancer Center
🇯🇵Ina, Saitama, Japan
National Hospital Organization Nagoya Medical Center
🇯🇵Nagoya, Aichi, Japan
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Gunma Prefectural Cancer Center
🇯🇵Ota, Gunma, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Kanagawa, Japan
Kanagawa Cancer Center - Thora
🇯🇵Yokohama-shi, Kanagawa, Japan
Kanagawa Cardiovascular and Respiratory Center
🇯🇵Yokohama, Kanagawa, Japan
Sasebo City General Hospital
🇯🇵Sasebo, Nagasaki, Japan
Kurashiki Central Hospital
🇯🇵Kurashiki, Okayama, Japan
Kansai Medical University Hirakata Hospital
🇯🇵Hirakata, Osaka, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka City, Osaka, Japan
National Hospital Organization Kinki-chuo Chest Medical Center
🇯🇵Sakai-shi, Osaka, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Takatsuki, Osaka, Japan
Hiroshima City Hiroshima Citiz
🇯🇵Hiroshima, Japan
Nagasaki University Hospital
🇯🇵Nagasaki, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan