Clinical Trials List
Protocol NumberTCD14678
NCT Number(ClinicalTrials.gov Identfier)NCT03192345
2020-07-01 - 2022-01-17
Phase I
Recruiting1
Terminated2
ICD-10C45.9
Mesothelioma, unspecified
ICD-10C79.9
Secondary malignant neoplasm of unspecified site
ICD-10C7A.00
Malignant carcinoid tumor of unspecified site
ICD-10C7A.094
Malignant carcinoid tumor of the foregut NOS
ICD-10C7A.095
Malignant carcinoid tumor of the midgut NOS
ICD-10C7A.096
Malignant carcinoid tumor of the hindgut NOS
ICD-10C7A.1
Malignant poorly differentiated neuroendocrine tumors
ICD-10C7A.8
Other malignant neuroendocrine tumors
ICD-10C7B.00
Secondary carcinoid tumors, unspecified site
ICD-10C80.1
Malignant (primary) neoplasm, unspecified
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9199.1
Malignant neoplasm of unspecified site (primary) (secondary)
A Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination With Cemiplimab in Adult Patients With Advanced Solid Tumors
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Trial Applicant
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Sponsor
Sanofi
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ann-Lii Cheng Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
- YEN-TING LIN Division of Hematology & Oncology
- James Chih-Hsin Yang Division of Hematology & Oncology
- Ying-Chun Shen Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- 吳尚俊 Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
- Chong-Jen Yu Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- 蔡子修 Division of Hematology & Oncology
- TSUNG-HAO LIU Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
- 楊景堯 Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shang-Yin Wu Division of General Internal Medicine
- 劉奕廷 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chia-Yen Dai Digestive System Department
- Wan-Long Chuang Digestive System Department
- Chung-Feng Huang Digestive System Department
- Shinn-Cherng Chen Digestive System Department
- 黃駿逸 Digestive System Department
- Jee-Fu Huang Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Malignant Solid Tumor
Objectives
Primary Objectives:
Dose escalation (Part 1)
Part 1A (SAR439459 monotherapy)
To determine the maximum tolerated dose (MTD) and/or maximum administered dose (MAD) of SAR439459 when administered intravenously as monotherapy in adult patients with advanced solid tumors.
Part 1B (SAR439459 and cemiplimab combination therapy)
To determine the MTD and/or MAD of SAR439459 administered intravenously in combination with cemiplimab administered intravenously in adult patients with advanced solid tumors.
Dose expansion (Part 2)
Part 2A (SAR439459 monotherapy)
To determine optimal dose of SAR439459 administered intravenously in adult patients with advanced melanoma who have failed a prior therapy based on anti-PD-1 (programmed cell death-1) or anti-PD-L1.
Part 2B (SAR439459 and cemiplimab combination therapy)
To determine the objective response rate (ORR) of SAR439459 in combination with cemiplimab in adult patients with selected advanced solid tumors by evaluation of antitumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).
Secondary Objectives:
Pharmacokinetic (PK) profile SAR439459 monotherapy and combined with cemiplimab, PK profile of cemiplimab combined with SAR439459.
Immunogenicity of SAR439459 monotherapy and combined with cemiplimab.
Dose escalation (Part 1)
Overall safety/tolerability profile of SAR439459 monotherapy and combined with cemiplimab.
Preliminary recommended phase 2 dose (pRP2D) of SAR439459 as monotherapy or combined with cemiplimab.
Dose expansion (Part 2)
Progression free survival (PFS), time to progression (TTP), ORR, and safety of SAR439459 as monotherapy and PFS, TTP, duration of response (DOR), disease control rate (DCR) and safety in combination with cemiplimab.
To confirm the optimal dose of SAR439459 administered in combination with cemiplimab.
Test Drug
SAR439459
Active Ingredient
SAR439459
Dosage Form
Vial
Dosage
22.5
Endpoints
Primary Outcome Measures :
Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Through the end of 1 or 2 cycles, total duration up to 6 weeks (for Part 1A each cycle is 2 weeks; for Part 1B each cycle is 2 or 3 weeks) ]
Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B.
Objective Response Rate (ORR) for Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2B).
Secondary Outcome Measures :
Overall safety profile [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The overall safety profile of SAR439459 administered in monotherapy (Part 1A and Part 2A) or in combination with cemiplimab (Part 1B and Part 2B).
Progression free survival (PFS) [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).
Time to progression (TTP) [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The time from first IMP administration until objective tumor progression (Part 2A and 2B).
Objective Response Rate (ORR) Part 2A [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2A).
Duration of response Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Time from initial response to the first documented tumor progression.
Disease Control Rate Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Sum of complete response, partial response and stable disease rates
Immunogenicity evaluation [ Time Frame: Up to approximately 1 year ]
Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B).
Cmax for SAR439459 and for cemiplimab [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Maximum plasma concentration observed.
AUC for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Area under the serum concentration versus time curve extrapolated to infinity.
AUC0-tau for SAR439459 and for cemiplimab [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 14 or 21 days post-dose.
t1/2z for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Terminal half-life associated with the terminal slope (λz).
CL for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.
Vss for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Estimate of Volume of distribution at the steady state after single intravenous dose.
Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Through the end of 1 or 2 cycles, total duration up to 6 weeks (for Part 1A each cycle is 2 weeks; for Part 1B each cycle is 2 or 3 weeks) ]
Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B.
Objective Response Rate (ORR) for Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2B).
Secondary Outcome Measures :
Overall safety profile [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The overall safety profile of SAR439459 administered in monotherapy (Part 1A and Part 2A) or in combination with cemiplimab (Part 1B and Part 2B).
Progression free survival (PFS) [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).
Time to progression (TTP) [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
The time from first IMP administration until objective tumor progression (Part 2A and 2B).
Objective Response Rate (ORR) Part 2A [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2A).
Duration of response Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Time from initial response to the first documented tumor progression.
Disease Control Rate Part 2B [ Time Frame: Continuous throughout study assessment (up to approximately 1 year) ]
Sum of complete response, partial response and stable disease rates
Immunogenicity evaluation [ Time Frame: Up to approximately 1 year ]
Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B).
Cmax for SAR439459 and for cemiplimab [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Maximum plasma concentration observed.
AUC for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Area under the serum concentration versus time curve extrapolated to infinity.
AUC0-tau for SAR439459 and for cemiplimab [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 14 or 21 days post-dose.
t1/2z for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Terminal half-life associated with the terminal slope (λz).
CL for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.
Vss for SAR439459 [ Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22 ]
Estimate of Volume of distribution at the steady state after single intravenous dose.
Inclution Criteria
Inclusion criteria:
Dose escalation (Part 1A and Part 1B)
Patients with histologically confirmed, advanced unresectable or metastatic solid tumor whom in the opinion of the Investigator does not have a suitable alternative therapy.
Dose expansion (Part 2A)
Patients with histologically confirmed, advanced unresectable or metastatic melanoma whom in the opinion of the Investigator does not have a suitable alternative therapy.
Patients must have failed after any prior therapy based on anti-PD-1 or anti-PD-L1 as defined by disease progression within 26 weeks of initiating anti-PD-1 or anti-PD-L1 based therapy without any evidence of a response (primary resistance to anti-PD-1 or anti-PD-L1).
Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. Patients must be able and willing to provide mandatory tumor biopsies prior to and during study treatment.
Dose expansion (Part 2B)
Patients with disease location amenable to mandatory tumor biopsy at baseline with histologically confirmed advanced unresectable or metastatic melanoma, colorectal adenocarcinoma, urothelial cancer, hepatocellular carcinoma (HCC), or non-small cell lung cancer (NSCLC).
Melanoma patients must have failed one prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with colorectal cancer must have progressed after last line of therapy.
Patients with urothelial cancer must have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Patients must not have received >2 lines of therapy for advanced disease. Patients must not have received prior treatment with anti-PD-1 or anti-PD-L1.
Patients with HCC must have failed after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with NSCLC must have failed during or after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with histologically confirmed, advanced unresectable or metastatic melanoma, or colorectal cancer or NSCLC whom in the opinion of the Investigator do not have a suitable alternative therapy.
Dose expansion parts 2A and 2B
At least 1 measurable lesion by RECIST v1.1.
All cohorts
Patient understands and has signed Informed Consent form and is willing and able to comply with the requirements of the trial.
Dose escalation (Part 1A and Part 1B)
Patients with histologically confirmed, advanced unresectable or metastatic solid tumor whom in the opinion of the Investigator does not have a suitable alternative therapy.
Dose expansion (Part 2A)
Patients with histologically confirmed, advanced unresectable or metastatic melanoma whom in the opinion of the Investigator does not have a suitable alternative therapy.
Patients must have failed after any prior therapy based on anti-PD-1 or anti-PD-L1 as defined by disease progression within 26 weeks of initiating anti-PD-1 or anti-PD-L1 based therapy without any evidence of a response (primary resistance to anti-PD-1 or anti-PD-L1).
Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. Patients must be able and willing to provide mandatory tumor biopsies prior to and during study treatment.
Dose expansion (Part 2B)
Patients with disease location amenable to mandatory tumor biopsy at baseline with histologically confirmed advanced unresectable or metastatic melanoma, colorectal adenocarcinoma, urothelial cancer, hepatocellular carcinoma (HCC), or non-small cell lung cancer (NSCLC).
Melanoma patients must have failed one prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with colorectal cancer must have progressed after last line of therapy.
Patients with urothelial cancer must have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Patients must not have received >2 lines of therapy for advanced disease. Patients must not have received prior treatment with anti-PD-1 or anti-PD-L1.
Patients with HCC must have failed after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with NSCLC must have failed during or after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
Patients with histologically confirmed, advanced unresectable or metastatic melanoma, or colorectal cancer or NSCLC whom in the opinion of the Investigator do not have a suitable alternative therapy.
Dose expansion parts 2A and 2B
At least 1 measurable lesion by RECIST v1.1.
All cohorts
Patient understands and has signed Informed Consent form and is willing and able to comply with the requirements of the trial.
Exclusion Criteria
Exclusion criteria:
Age <18 years or < the country's legal age of majority if the legal age is more than 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status >1.
Concurrent treatment with any other anticancer therapy (including radiotherapy or investigational agents) or participation in another clinical study.
Washout period of less than 3 weeks to prior anticancer therapy.
Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy by using highly effective contraceptive.
Pregnant or breast-feeding women.
Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Significant and uncontrolled concomitant illness, including any psychiatric condition.
Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic therapy within 1 week prior to enrollment.
Any prior organ transplant including allogeneic bone marrow transplant.
History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
History of known human immunodeficiency virus (HIV), HIV serology at screening will be conducted only for patients in German study sites.
Known uncontrolled hepatitis B virus (HBV) infection.
Known untreated current hepatitis C virus (HCV) infection.
Any major surgery within the last 28 days.
Patients with primary central nervous system (CNS) tumors and/or CNS metastases of non-CNS primary tumors.
History of congestive heart failure, myocardial infarction with reduced ejection fraction, symptomatic coronary artery disease, documented uncontrolled hypertension, major clinically significant Electrocardiography (ECG) and echocardiogram abnormalities, significant ventricular arrhythmias, significant valvular heart disease (including valve replacement), vascular malformation, aneurysm, significant pulmonary conditions such as idiopathic pulmonary hypertension, uncontrolled chronic lung disease.
History of severe, acute or chronic renal diseases.
Any of the following within 6 months prior to study enrollment: pulmonary embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage.
Inadequate hematological, renal or liver function.
Non-resolution of any prior treatment related toxicity to Grade <2.
Prior treatment with any anti-transforming growth factor β (anti-TGFβ) inhibitors.
Known allergies to any component of SAR439459 and/or cemiplimab.
Patients with uveal melanoma and patients with prior or ongoing uveitis.
Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy.
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of SAR439459 and/or cemiplimab (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).
History of interstitial lung disease or active non-infectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
Patients with underlying cancer predisposition syndromes.
Receipt of a live vaccine within 30 days of planned start of study medication.
Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the first dose of SAR439459.
Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of normal (ULN).
Patients accommodated in an institution because of regulatory or legal order; prisoners or patients who are legally institutionalized.
Age <18 years or < the country's legal age of majority if the legal age is more than 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status >1.
Concurrent treatment with any other anticancer therapy (including radiotherapy or investigational agents) or participation in another clinical study.
Washout period of less than 3 weeks to prior anticancer therapy.
Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy by using highly effective contraceptive.
Pregnant or breast-feeding women.
Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Significant and uncontrolled concomitant illness, including any psychiatric condition.
Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic therapy within 1 week prior to enrollment.
Any prior organ transplant including allogeneic bone marrow transplant.
History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
History of known human immunodeficiency virus (HIV), HIV serology at screening will be conducted only for patients in German study sites.
Known uncontrolled hepatitis B virus (HBV) infection.
Known untreated current hepatitis C virus (HCV) infection.
Any major surgery within the last 28 days.
Patients with primary central nervous system (CNS) tumors and/or CNS metastases of non-CNS primary tumors.
History of congestive heart failure, myocardial infarction with reduced ejection fraction, symptomatic coronary artery disease, documented uncontrolled hypertension, major clinically significant Electrocardiography (ECG) and echocardiogram abnormalities, significant ventricular arrhythmias, significant valvular heart disease (including valve replacement), vascular malformation, aneurysm, significant pulmonary conditions such as idiopathic pulmonary hypertension, uncontrolled chronic lung disease.
History of severe, acute or chronic renal diseases.
Any of the following within 6 months prior to study enrollment: pulmonary embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage.
Inadequate hematological, renal or liver function.
Non-resolution of any prior treatment related toxicity to Grade <2.
Prior treatment with any anti-transforming growth factor β (anti-TGFβ) inhibitors.
Known allergies to any component of SAR439459 and/or cemiplimab.
Patients with uveal melanoma and patients with prior or ongoing uveitis.
Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy.
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of SAR439459 and/or cemiplimab (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).
History of interstitial lung disease or active non-infectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
Patients with underlying cancer predisposition syndromes.
Receipt of a live vaccine within 30 days of planned start of study medication.
Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the first dose of SAR439459.
Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of normal (ULN).
Patients accommodated in an institution because of regulatory or legal order; prisoners or patients who are legally institutionalized.
The Estimated Number of Participants
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Taiwan
18 participants
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Global
264 participants
