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

Advanced Malignancies Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03233139
• Other study ID #: R2810-ONC-1622
• Status: Recruiting
• Phase: Phase 1
• Start date: June 21, 2017
• Est. completion date: March 27, 2030

Study information

• Verified date: September 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 145
• Est. completion date: March 27, 2030
• Est. primary completion date: December 22, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms

Intervention

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.
• Ipilimumab
To be administered per protocol
• Platinum-doublet chemotherapy
To be administered per protocol
• Gemcitabine
To be administered per protocol
• Pemetrexed
To be administered per protocol
• Paclitaxel
To be administered per protocol
• Fianlimab
To be administered per protocol

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Cho-Ku	Tokyo
Japan	Gunma Prefectural Cancer Center	Gunma
Japan	Kansai Medical University Hospital	Hirakata	Osaka
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	Saitama Cancer Center	Kita Adachi	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Kurashiki Central Hospital	Kurashiki	Okayama
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Nagasaki University Hospital	Nagasaki
Japan	Nagoya Medical Center	Nagoya	Aichi
Japan	Osaka City University Hospital	Osaka
Japan	Osaka International Cancer Center	Osaka
Japan	Kitasato University Hospital	Sagamihara	Kanagawa
Japan	Kinki-Chuo Chest Medical Center	Sakai	Osaka
Japan	Sasebo City General Hospital	Sasebo	Nagasaki
Japan	Tokyo Medical University Hospital	Shinjuku	Tokyo
Japan	Osaka Medical College Hospital	Takatsuki	Osaka
Japan	Tokushima University Hospital	Tokushima
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Japan	Kanagawa Cardiovascular and Respiratory Center	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with cemiplimab as monotherapy		Up to 136 weeks
Primary	Incidence and severity of TEAEs in patients treated with cemiplimab in combination with other agents		Up to 136 weeks
Primary	Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab without chemotherapy		Up to 136 weeks
Primary	Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab with chemotherapy		Up to 136 weeks
Primary	PK of cemiplimab: Cmax	Peak serum concentration	Up to 136 weeks
Primary	PK of cemiplimab: tmax	Time to Cmax	Up to 136 weeks
Primary	PK of cemiplimab: Ctrough	Drug concentration in serum at the end of a dosing interval	Up to 136 weeks
Primary	PK of cemiplimab: Area under the drug concentration-time curve in serum (AUC3w)	AUC over a 3-week dosing interval	Up to 136 weeks
Primary	PK of cemiplimab: t½ estimated over a 3-week dosing interval	Observed terminal half-life	Up to 136 weeks
Secondary	Immunogenicity against cemiplimab and fianlimab	Evaluate the immunogenicity of cemiplimab and fianlimab after single-dose administration	Up to 136 weeks
Secondary	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
Secondary	Duration of Response (DOR)	As assessed by an IRC (per RECIST1.1) in Part 2, Cohorts A and C	Up to 136 weeks