Clinical trial NCT03233139: Safety and Pharmacokinetics of Cemiplimab Anti-programmed Death-ligand 1 (Anti-PD-1) and Other Agents in Japanese Adult Patients With Advanced Malignancies
Official title: A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Cemiplimab (Anti-PD-1) and Other Agents in Japanese Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Malignancies
Keywords: Japanese patients
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-07-28
Enrollment: 146
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility 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/exclusion criteria apply.

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with cemiplimab as monotherapy
timeFrame: Up to 136 weeks
measure: Incidence and severity of TEAEs in patients treated with cemiplimab in combination with other agents
timeFrame: Up to 136 weeks
measure: Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab without chemotherapy
timeFrame: Up to 136 weeks
measure: Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab with chemotherapy
timeFrame: Up to 136 weeks
measure: PK of cemiplimab: Cmax
timeFrame: Up to 136 weeks
measure: PK of cemiplimab: tmax
timeFrame: Up to 136 weeks
measure: PK of cemiplimab: Ctrough
timeFrame: Up to 136 weeks
measure: PK of cemiplimab: Area under the drug concentration-time curve in serum (AUC3w)
timeFrame: Up to 136 weeks
measure: PK of cemiplimab: t½ estimated over a 3-week dosing interval
timeFrame: Up to 136 weeks
Secondary outcomes:
measure: Immunogenicity against cemiplimab and fianlimab
timeFrame: Up to 136 weeks
measure: Objective Response Rate (ORR)
timeFrame: Up to 135 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 136 weeks
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center - Thora
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cardiovascular and Respiratory Center
state: Kanagawa
city: Sasebo
country: Japan
facility: Sasebo City General Hospital
state: Nagasaki
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Hirakata
country: Japan
facility: Kansai Medical University Hirakata Hospital
state: Osaka
city: Osaka City
country: Japan
facility: Osaka Metropolitan University Hospital
state: Osaka
city: Sakai-shi
country: Japan
facility: National Hospital Organization Kinki-chuo Chest Medical Center
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
state: Osaka
city: Ina
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Chuo ku
country: Japan
facility: National Cancer Center Hospital - Tsukiji Campus
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citiz
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokushima
country: Japan
facility: Tokushima University Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.