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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03192345




Registration number
NCT03192345
Ethics application status
Date submitted
16/06/2017
Date registered
20/06/2017
Date last updated
12/05/2022

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

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


Other interventions: 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
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)
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
Terminated
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
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
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Estonia
State/province [12] 0 0
Tallinn
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Nantes
Country [16] 0 0
France
State/province [16] 0 0
Paris
Country [17] 0 0
France
State/province [17] 0 0
Villejuif
Country [18] 0 0
Germany
State/province [18] 0 0
Essen
Country [19] 0 0
Germany
State/province [19] 0 0
Hannover
Country [20] 0 0
Italy
State/province [20] 0 0
Milano
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul-teukbyeolsi
Country [22] 0 0
Netherlands
State/province [22] 0 0
Nijmegen
Country [23] 0 0
Netherlands
State/province [23] 0 0
Rotterdam
Country [24] 0 0
Netherlands
State/province [24] 0 0
Utrecht
Country [25] 0 0
Spain
State/province [25] 0 0
Barcelona [Barcelona]
Country [26] 0 0
Spain
State/province [26] 0 0
Madrid, Comunidad De
Country [27] 0 0
Spain
State/province [27] 0 0
Navarra
Country [28] 0 0
Taiwan
State/province [28] 0 0
Kaohsiung
Country [29] 0 0
Taiwan
State/province [29] 0 0
Tainan
Country [30] 0 0
Taiwan
State/province [30] 0 0
Taipei 100
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Central Bedfordshire
Country [32] 0 0
United Kingdom
State/province [32] 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
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.
Trial website
https://clinicaltrials.gov/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03192345