Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03192345
Other study ID # TCD14678
Secondary ID 2018-001113-32
Status Terminated
Phase Phase 1
First received
Last updated
Start date June 9, 2017
Est. completion date January 17, 2022

Study information

Verified date February 4, 2022
Source Sanofi
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 4 weeks (28 days), a treatment period of at least 1 or 2 cycles (21 or 14 days per cycle, respectively), an end-of-treatment visit at least 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier. For the urothelial cancer cohort in Part 2B, follow-up visits will occur every 3 months until death, study cut-off date, or upon cancellation of Survival follow-up at the discretion of the Sponsor at any prior timepoint. For the overall survival analysis (approximately 12 months after last patient first dose), whichever comes first. Patients who have no disease progression, and continue to benefit from the study drug(s), will be allowed to continue treatment beyond the common study end-date at their assigned dose unless the study is terminated by the Sponsor. The expected enrollment period is approximately 42 months.


Recruitment information / eligibility

Status Terminated
Enrollment 161
Est. completion date January 17, 2022
Est. primary completion date December 21, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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. 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 ß (anti-TGFß) 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 above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
SAR439459
Pharmaceutical form: powder for solution for infusion Route of administration: intravenous infusion
Drug:
Cemiplimab REGN2810
Pharmaceutical form: solution for infusion Route of administration: intravenous infusion

Locations

Country Name City State
Australia Investigational Site Number :0360002 Heidelberg West Victoria
Australia Investigational Site Number :0360001 Melbourne Victoria
Belgium Investigational Site Number :0560002 Bruxelles
Belgium Investigational Site Number :0560001 Leuven
Canada Investigational Site Number :1240003 Calgary Alberta
Canada Investigational Site Number :1240002 Montreal Quebec
Canada Investigational Site Number :1240001 Toronto Ontario
Estonia Investigational Site Number :2330001 Tallinn
France Investigational Site Number :2500006 Lille
France Investigational Site Number :2500002 Marseille
France Investigational Site Number :2500003 Nantes
France Investigational Site Number :2500005 Nantes
France Investigational Site Number :2500004 Paris
France Investigational Site Number :2500001 Villejuif
Germany Investigational Site Number :2760001 Essen
Germany Investigational Site Number :2760003 Hannover
Italy Investigational Site Number :3800001 Milano
Italy Investigational Site Number :3800002 Milano
Italy Investigational Site Number :3800003 Rozzano Milano
Korea, Republic of Investigational Site Number :4100001 Seoul Seoul-teukbyeolsi
Korea, Republic of Investigational Site Number :4100002 Seoul Seoul-teukbyeolsi
Netherlands Investigational Site Number :5280005 Nijmegen
Netherlands Investigational Site Number :5280001 Rotterdam
Netherlands Investigational Site Number :5280002 Utrecht
Spain Investigational Site Number :7240001 Barcelona Barcelona [Barcelona]
Spain Investigational Site Number :7240002 Barcelona Barcelona [Barcelona]
Spain Investigational Site Number :7240006 Barcelona Barcelona [Barcelona]
Spain Investigational Site Number :7240003 Madrid / Madrid Madrid, Comunidad De
Spain Investigational Site Number :7240004 Madrid / Madrid Madrid, Comunidad De
Spain Investigational Site Number :7240005 Pamplona Navarra
Taiwan Investigational Site Number :1580003 Kaohsiung
Taiwan Investigational Site Number :1580002 Tainan
Taiwan Investigational Site Number :1580001 Taipei 100
United Kingdom Investigational Site Number :8260002 Cardiff Vale Of Glamorgan, The
United Kingdom Investigational Site Number :8260001 Glasgow Central Bedfordshire
United States Investigational Site Number :8400001 Boston Massachusetts
United States Investigational Site Number :8400101 Boston Massachusetts
United States Investigational Site Number :8400003 Dallas Texas
United States Investigational Site Number :8400007 Duarte California
United States Investigational Site Number :8400008 Durham North Carolina
United States Investigational Site Number :8400004 Fairway Kansas
United States Investigational Site Number :8400006 Nashville Tennessee

Sponsors (1)

Lead Sponsor Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Estonia,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Dose Limiting Toxicities (DLTs) Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B. 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)
Primary Objective Response Rate (ORR) for Part 2B Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2B). Continuous throughout study assessment (up to approximately 1 year)
Secondary Overall safety profile The overall safety profile of SAR439459 administered in monotherapy (Part 1A and Part 2A) or in combination with cemiplimab (Part 1B and Part 2B). Continuous throughout study assessment (up to approximately 1 year)
Secondary Progression free survival (PFS) The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B). Continuous throughout study assessment (up to approximately 1 year)
Secondary Time to progression (TTP) The time from first IMP administration until objective tumor progression (Part 2A and 2B). Continuous throughout study assessment (up to approximately 1 year)
Secondary Objective Response Rate (ORR) Part 2A Efficacy as documented by ORR will be assessed by evaluation of antitumor response information according to RECIST 1.1 (Part 2A). Continuous throughout study assessment (up to approximately 1 year)
Secondary Duration of response Part 2B Time from initial response to the first documented tumor progression. Continuous throughout study assessment (up to approximately 1 year)
Secondary Disease Control Rate Part 2B Sum of complete response, partial response and stable disease rates Continuous throughout study assessment (up to approximately 1 year)
Secondary Immunogenicity evaluation Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B). Up to approximately 1 year
Secondary Cmax for SAR439459 and for cemiplimab Maximum plasma concentration observed. Cycle 1, Day 1 to Day 15 or to Day 22
Secondary AUC for SAR439459 Area under the serum concentration versus time curve extrapolated to infinity. Cycle 1, Day 1 to Day 15 or to Day 22
Secondary AUC0-tau for SAR439459 and for cemiplimab Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to 14 or 21 days post-dose. Cycle 1, Day 1 to Day 15 or to Day 22
Secondary t1/2z for SAR439459 Terminal half-life associated with the terminal slope (?z). Cycle 1, Day 1 to Day 15 or to Day 22
Secondary CL for SAR439459 Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1. Cycle 1, Day 1 to Day 15 or to Day 22
Secondary Vss for SAR439459 Estimate of Volume of distribution at the steady state after single intravenous dose. Cycle 1, Day 1 to Day 15 or to Day 22
See also
  Status Clinical Trial Phase
Terminated NCT01846429 - Oral Bicarbonate as Adjuvant for Pain Reduction in Patients With Tumor Related Pain Phase 1
Completed NCT01359982 - Safety and Pharmacokinetic Study of RRx-001 in Cancer Subjects Phase 1
Completed NCT00725634 - A Phase 1 Dose-Escalation Study in Advanced Solid Tumors, Lymphomas or Multiple Myeloma Phase 1
Completed NCT01648764 - A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread Phase 1
Recruiting NCT04083599 - GEN1042 Safety Trial and Anti-tumor Activity in Subjects With Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT05141474 - Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors Early Phase 1
Active, not recruiting NCT02999750 - EXtendedAnalysis for Cancer Treatment N/A
Completed NCT01457118 - An Extension Study of NKTR-102 in Cancer Patients Previously Enrolled in NKTR-102 Studies Phase 2
Active, not recruiting NCT05539157 - Study to Evaluate JCXH-211 as Monotherapy in Patients With Malignant Solid Tumors Phase 1
Recruiting NCT04571892 - A Clinical Study to Observe the Safety and Efficacy of ScTIL210 in the Treatment of Malignant Solid Tumors Phase 1/Phase 2
Recruiting NCT05468359 - Safety and Efficacy of Cyclophosphamide, Sorafenib, Bevacizumab, and Atezolizumab in Pediatric Solid Tumor Patients Phase 1/Phase 2
Recruiting NCT04168528 - Phase I/IIa Study of 68GaNOTA-Anti-MMR-VHH2 for PET/CT Phase 1/Phase 2
Recruiting NCT04145622 - Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors Phase 1/Phase 2
Recruiting NCT06057038 - A Safety Trial of GEN1042 in Japanese Subjects With Malignant Solid Tumors Phase 1
Completed NCT02844400 - Cancer Patients' Performance Status Assessed Using Cardiopulmonary Exercise Testing and Wearable Data Generation
Completed NCT00452413 - A Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer Phase 1/Phase 2
Completed NCT03553108 - A Study Using Olaparib Tablets for Subjects With Advanced Solid Tumours. Phase 1
Recruiting NCT06391775 - Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy Phase 1/Phase 2
Recruiting NCT04076137 - Targeted T-cell Therapy in Solid Tumors Early Phase 1
Completed NCT02754141 - An Investigational Immuno-therapy Study of Experimental Medication BMS-986179 Given Alone and in Combination With Nivolumab Phase 1/Phase 2