Source: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=18587&isClinicalTrial=True
Timestamp: 2020-07-04 18:41:43
Document Index: 17902534

Matched Legal Cases: ['arts 1', 'art 1', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2', 'art 1', 'art 2', 'art 2', 'art 2', 'art 2', 'art 2', 'art 2', 'art 2', 'arts 1']

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03192345
2018-001113-32
Other interventions - SAR439459
Experimental: Dose Escalation SAR439459 monotherapy - SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses
Experimental: Dose Expansion SAR439459 monotherapy - 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
Experimental: Dose Escalation SAR439459 + cemiplimab combination - 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 at a standard dose
Experimental: Dose Expansion SAR439459 + cemiplimab combination - SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab at a standard dose
Other interventions: SAR439459
Incidence of Dose Limiting Toxicities (DLTs) - Incidence of DLTs at Cycle 1 and 2 in Parts 1A and 1B.
Through the end of two 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)
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)
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).
Progression free survival (PFS) - The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).
Time to progression (TTP) - The time from first IMP administration until objective tumor progression (Part 2A and 2B).
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).
Duration of response Part 2B (urothelial cancer cohort only) - Time from initial response to the first documented tumor progression.
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
Cmax for SAR439459 and for cemiplimab - Maximum plasma concentration observed.
Cycle 1, Day 1 to Day 15 or to Day 22
AUC for SAR439459 - Area under the serum concentration versus time curve extrapolated to infinity.
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.
t1/2z for SAR439459 - Terminal half-life associated with the terminal slope (?z).
CL for SAR439459 - Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.
Vss for SAR439459 - Estimate of Volume of distribution at the steady state after single intravenous dose.
- Patients with histologically confirmed, advanced unresectable or metastatic solid
- Patients with histologically confirmed, advanced unresectable or metastatic melanoma
- Patients must have failed a prior therapy based on anti-PD-1 or anti-PD-L1 as defined
- Patients must have a site of disease amenable to biopsy and be a candidate for tumor
- Patients with histologically confirmed advanced unresectable or metastatic melanoma or
- 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
lines of therapy for advanced disease. Patients must not have received prior treatment
with anti-PD-1 or anti-PD-L1.
- Patients with histologically confirmed, advanced unresectable or metastatic melanoma,
or colorectal cancer whom in the opinion of the Investigator do not have a suitable
- At least 1 measurable lesion by RECIST v1.1.
- Patient understands and has signed Informed Consent form and is willing and able to
- Concurrent treatment with any other anticancer therapy (including radiotherapy or
- 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
- Unwillingness and inability to comply with scheduled visits, drug administration plan,
- Significant and uncontrolled concomitant illness, including any psychiatric condition.
- Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic
- Any prior organ transplant including allogeneic bone marrow transplant.
- History within the last 5 years of an invasive malignancy other than the one treated
- History of known human immunodeficiency virus (HIV), unresolved viral hepatitis, HIV
serology at screening will be conducted only for patients in German study sites.
- Patients with primary central nervous system (CNS) tumors and/or CNS metastases of
- History of severe, congestive heart failure, myocardial infarction with reduced
- History of severe, acute or chronic renal diseases.
- Any of the following within 6 months prior to study enrollment: pulmonary embolism,
- 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
- History of interstitial lung disease or active non-infectious pneumonitis that
- 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
- Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of
- Patients accommodated in an institution because of regulatory or legal order;
prisoners or patients who are legally institutionalized.
Investigational Site Number 0360002 - Heidelberg West
Investigational Site Number 0360001 - Melbourne
- 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
- To determine the MTD and/or MAD of SAR439459 administered intravenously in combination
with cemiplimab administered intravenously in adult patients with advanced solid tumors.
- 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.
- 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
- Pharmacokinetic (PK) profile SAR439459 monotherapy and combined with cemiplimab, PK
profile of cemiplimab combined with SAR439459.
- Immunogenicity of SAR439459 monotherapy and combined with cemiplimab.
- Overall safety/tolerability profile of SAR439459 monotherapy and combined with
- Preliminary recommended phase 2 dose (pRP2D) of SAR439459 as monotherapy or combined
with cemiplimab.
- Progression free survival (PFS), time to progression (TTP), ORR, and safety of SAR439459
as monotherapy and PFS, TTP and safety in combination with cemiplimab in adult patients
with advanced melanoma who have failed a prior therapy based on anti-PD-1 or anti-PD-L1
and patients with mesenchymal Colorectal cancer.
- PFS, duration of response (DOR) and safety in adult patients with metastatic urothelial
- To confirm the optimal dose of SAR439459 administered in combination with cemiplimab.
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03192345