Advanced Malignancies
Conditions
Keywords
Japanese patients
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.
Interventions
DRUGCemiplimab
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.
DRUGIpilimumab
To be administered per protocol
To be administered per protocol
DRUGGemcitabine
To be administered per protocol
DRUGPemetrexed
To be administered per protocol
DRUGPaclitaxel
To be administered per protocol
DRUGFianlimab
To be administered per protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| PK of cemiplimab: Cmax | Up to 136 weeks | Peak serum concentration |
| PK of cemiplimab: tmax | Up to 136 weeks | Time to Cmax |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity against cemiplimab and fianlimab | Up to 136 weeks | Evaluate the immunogenicity of cemiplimab and fianlimab after single-dose administration |
| 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 |
Countries
Japan
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed