A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and Cemiplimab in Patients With Advanced Solid Tumors
- Conditions
- Malignant Solid Tumor
- Interventions
- Biological: SAR439459
- Registration Number
- NCT03192345
- Lead Sponsor
- Sanofi
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 161
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation SAR439459 monotherapy SAR439459 SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses Dose Expansion SAR439459 + cemiplimab combination SAR439459 SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab Dose Expansion SAR439459 monotherapy SAR439459 SAR439459 administered intravenously every 3 weeks in a 21-day cycle with the previously determined recommended doses as the patients will be randomized to 2 different doses Dose Escalation SAR439459 + cemiplimab combination SAR439459 SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab Dose Escalation SAR439459 + cemiplimab combination Cemiplimab REGN2810 SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab Dose Expansion SAR439459 + cemiplimab combination Cemiplimab REGN2810 SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLTs) 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 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
Name Time Method Immunogenicity evaluation 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).
Vss for SAR439459 Cycle 1, Day 1 to Day 15 or to Day 22 Estimate of Volume of distribution at the steady state after single intravenous dose.
Overall safety profile 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) 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) 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 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 Continuous throughout study assessment (up to approximately 1 year) Time from initial response to the first documented tumor progression.
Disease Control Rate Part 2B Continuous throughout study assessment (up to approximately 1 year) Sum of complete response, partial response and stable disease rates
CL for SAR439459 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.
Cmax for SAR439459 and for cemiplimab Cycle 1, Day 1 to Day 15 or to Day 22 Maximum plasma concentration observed.
AUC0-tau for SAR439459 and for cemiplimab 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.
AUC for SAR439459 Cycle 1, Day 1 to Day 15 or to Day 22 Area under the serum concentration versus time curve extrapolated to infinity.
t1/2z for SAR439459 Cycle 1, Day 1 to Day 15 or to Day 22 Terminal half-life associated with the terminal slope (λz).
Trial Locations
- Locations (34)
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
Tennessee Oncology, PLLC Site Number : 8400006
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research Center Site Number : 8400003
🇺🇸Dallas, Texas, United States
Investigational Site Number : 5280001
🇳🇱Rotterdam, Netherlands
Investigational Site Number : 3800003
🇮🇹Rozzano, Milano, Italy
Investigational Site Number : 3800002
🇮🇹Milano, Italy
Investigational Site Number : 2500005
🇫🇷Nantes, France
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 2760001
🇩🇪Essen, Germany
Investigational Site Number : 7240001
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 8260002
🇬🇧Cardiff, Vale Of Glamorgan, The, United Kingdom
Investigational Site Number : 2500001
🇫🇷Villejuif, France
Investigational Site Number : 7240002
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 1240002
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 2760003
🇩🇪Hannover, Germany
Investigational Site Number : 1580002
🇨🇳Tainan, Taiwan
Investigational Site Number : 5280002
🇳🇱Utrecht, Netherlands
Investigational Site Number : 3800001
🇮🇹Milano, Italy
Investigational Site Number : 2500002
🇫🇷Marseille, France
The University of Kansas Clinical Research Center Site Number : 8400004
🇺🇸Fairway, Kansas, United States
Massachusetts General Hospital Site Number : 8400001
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute Site Number : 8400101
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center Site Number : 8400008
🇺🇸Durham, North Carolina, United States
Investigational Site Number : 0360002
🇦🇺Heidelberg West, Victoria, Australia
Investigational Site Number : 0360001
🇦🇺Melbourne, Victoria, Australia
Investigational Site Number : 1240001
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 2330001
🇪🇪Tallinn, Estonia
Investigational Site Number : 2500003
🇫🇷Nantes, France
Investigational Site Number : 4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
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, Spain
Investigational Site Number : 8260001
🇬🇧Glasgow, Central Bedfordshire, United Kingdom
Investigational Site Number : 1240003
🇨🇦Calgary, Alberta, Canada