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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03192345




Registration number
NCT03192345
Ethics application status
Date submitted
16/06/2017
Date registered
20/06/2017
Date last updated
30/06/2020

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
2018-001113-32
Secondary ID [2] 0 0
TCD14678
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - SAR439459
Treatment: Drugs - Cemiplimab REGN2810

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
Pharmaceutical form: powder for solution for infusion
Route of administration: intravenous infusion

Treatment: Drugs: Cemiplimab REGN2810
Pharmaceutical form: solution
Route of administration: intravenous infusion

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicities (DLTs) - Incidence of DLTs at Cycle 1 and 2 in Parts 1A and 1B.
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
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).
Timepoint [2] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [2] 0 0
Progression free survival (PFS) - The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).
Timepoint [2] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [3] 0 0
Time to progression (TTP) - The time from first IMP administration until objective tumor progression (Part 2A and 2B).
Timepoint [3] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [5] 0 0
Duration of response Part 2B (urothelial cancer cohort only) - Time from initial response to the first documented tumor progression.
Timepoint [5] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [6] 0 0
Immunogenicity evaluation - Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B).
Timepoint [6] 0 0
Up to approximately 1 year
Secondary outcome [7] 0 0
Cmax for SAR439459 and for cemiplimab - Maximum plasma concentration observed.
Timepoint [7] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [8] 0 0
AUC for SAR439459 - Area under the serum concentration versus time curve extrapolated to infinity.
Timepoint [8] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [10] 0 0
t1/2z for SAR439459 - Terminal half-life associated with the terminal slope (?z).
Timepoint [10] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [11] 0 0
CL for SAR439459 - Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.
Timepoint [11] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [12] 0 0
Vss for SAR439459 - Estimate of Volume of distribution at the steady state after single intravenous dose.
Timepoint [12] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22

Eligibility
Key inclusion 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 a prior therapy based on anti-PD-1 or anti-PD-L1 as defined
by disease progression confirmed radiologically within 12 weeks of commencing
treatment without any evidence of a response.

- Patients must have a site of disease amenable to biopsy and be a candidate for tumor
biopsy. Patients must be able to provide mandatory tumor biopsies prior to and during
study treatment.

Dose expansion (Part 2B)

- Patients with histologically confirmed advanced unresectable or metastatic melanoma or
colorectal adenocarcinoma or patients with urothelial cancer.

- 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 histologically confirmed, advanced unresectable or metastatic melanoma,
or colorectal cancer 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Age <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), unresolved viral hepatitis, HIV
serology at screening will be conducted only for patients in German study sites.

- 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 that are untreated.

- History of severe, 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360002 - Heidelberg West
Recruitment hospital [2] 0 0
Investigational Site Number 0360001 - Melbourne
Recruitment postcode(s) [1] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Canada
State/province [8] 0 0
Calgary
Country [9] 0 0
Canada
State/province [9] 0 0
Montreal
Country [10] 0 0
Canada
State/province [10] 0 0
Toronto
Country [11] 0 0
Estonia
State/province [11] 0 0
Tallinn
Country [12] 0 0
France
State/province [12] 0 0
Marseille Cedex 5
Country [13] 0 0
France
State/province [13] 0 0
Nantes
Country [14] 0 0
France
State/province [14] 0 0
Paris Cedex 10
Country [15] 0 0
France
State/province [15] 0 0
Villejuif Cedex
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Netherlands
State/province [17] 0 0
Rotterdam
Country [18] 0 0
Netherlands
State/province [18] 0 0
Utrecht
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid / Madrid
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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 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
cancer.

- To confirm the optimal dose of SAR439459 administered in combination with cemiplimab.
Trial website
https://clinicaltrials.gov/show/NCT03192345
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-Us@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03192345