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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03192345
Ethics application status
Date submitted
16/06/2017
Date registered
20/06/2017

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
TCD14678
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
Treatment: Other - 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

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


Treatment: Other: SAR439459
Pharmaceutical form: powder for solution for infusion

Route of administration: intravenous infusion

Treatment: Drugs: Cemiplimab REGN2810
Pharmaceutical form: solution for infusion

Route of administration: intravenous infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
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 outcome [2] 0 0
Objective Response Rate (ORR) for Part 2B
Timepoint [2] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [1] 0 0
Overall safety profile
Timepoint [1] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [2] 0 0
Progression free survival (PFS)
Timepoint [2] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [3] 0 0
Time to progression (TTP)
Timepoint [3] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [4] 0 0
Objective Response Rate (ORR) 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
Timepoint [5] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [6] 0 0
Disease Control Rate Part 2B
Timepoint [6] 0 0
Continuous throughout study assessment (up to approximately 1 year)
Secondary outcome [7] 0 0
Immunogenicity evaluation
Timepoint [7] 0 0
Up to approximately 1 year
Secondary outcome [8] 0 0
Cmax for SAR439459 and for cemiplimab
Timepoint [8] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [9] 0 0
AUC for SAR439459
Timepoint [9] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [10] 0 0
AUC0-tau for SAR439459 and for cemiplimab
Timepoint [10] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [11] 0 0
t1/2z for SAR439459
Timepoint [11] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [12] 0 0
CL for SAR439459
Timepoint [12] 0 0
Cycle 1, Day 1 to Day 15 or to Day 22
Secondary outcome [13] 0 0
Vss for SAR439459
Timepoint [13] 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 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/01/2022
Sample size
Target
Accrual to date
Final
161
Recruitment in Australia
Recruitment state(s)
VIC
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
Kansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Alberta
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Estonia
State/province [10] 0 0
Tallinn
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Nantes
Country [13] 0 0
France
State/province [13] 0 0
Villejuif
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Germany
State/province [15] 0 0
Hannover
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul-teukbyeolsi
Country [18] 0 0
Netherlands
State/province [18] 0 0
Rotterdam
Country [19] 0 0
Netherlands
State/province [19] 0 0
Utrecht
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona [Barcelona]
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid, Comunidad De
Country [22] 0 0
Spain
State/province [22] 0 0
Navarra
Country [23] 0 0
Taiwan
State/province [23] 0 0
Tainan
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Central Bedfordshire
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Vale Of Glamorgan, The

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Baranda JC, Robbrecht D, Sullivan R, Doger B, Sant... [More Details]


Results not provided in https://clinicaltrials.gov/study/NCT03192345