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Malignant Solid TumorPhase 1NCT03192345

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

A Phase 1 study testing SAR439459 and Cemiplimab REGN2810 in people with Malignant Solid Tumor, run by Sanofi at 34 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Solid Tumor
What is being tested?
SAR439459 and Cemiplimab REGN2810
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
161 participants
Where
34 sitesin 13 countries
Study dates
9 Jun 2017to 17 Jan 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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.

Who cannot join

  • 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.
Show all 34Show fewer
  • 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 β (anti-TGFβ) 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.

Trial locations and contacts

34 sites in 13 countries.

34 sites in 13 countries

United States6 sites

  • Massachusetts General Hospital Site Number : 8400001

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute Site Number : 8400101

    Boston, Massachusetts, 02115

  • Mary Crowley Cancer Research Center Site Number : 8400003

    Dallas, Texas, 75230

  • Duke University Medical Center Site Number : 8400008

    Durham, North Carolina, 27710

  • The University of Kansas Clinical Research Center Site Number : 8400004

    Fairway, Kansas, 66205

  • Tennessee Oncology, PLLC Site Number : 8400006

    Nashville, Tennessee, 37203

Other trials in United States

Spain5 sites

  • Investigational Site Number : 7240002

    Barcelona, Barcelona [Barcelona], 08003

  • Investigational Site Number : 7240001

    Barcelona, Barcelona [Barcelona], 08035

  • Investigational Site Number : 7240003

    Madrid / Madrid, Madrid, Comunidad de, 28040

  • Investigational Site Number : 7240004

    Madrid / Madrid, Madrid, Comunidad de, 28050

  • Investigational Site Number : 7240005

    Pamplona, Navarre, 31008

Other trials in Spain

France4 sites

  • Investigational Site Number : 2500002

    Marseille, 13385

  • Investigational Site Number : 2500003

    Nantes, 44093

  • Investigational Site Number : 2500005

    Nantes, 44093

  • Investigational Site Number : 2500001

    Villejuif, 94800

Other trials in France

Canada3 sites

  • Investigational Site Number : 1240003

    Calgary, Alberta, T2N 4N2

  • Investigational Site Number : 1240002

    Montreal, Quebec, H3T 1E2

  • Investigational Site Number : 1240001

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Italy3 sites

  • Investigational Site Number : 3800001

    Milan, 20133

  • Investigational Site Number : 3800002

    Milan, 20141

  • Investigational Site Number : 3800003

    Rozzano, Milano, 20089

Other trials in Italy

Australia2 sites

  • Investigational Site Number : 0360002

    Heidelberg West, Victoria, 3081

  • Investigational Site Number : 0360001

    Melbourne, Victoria, 3000

Other trials in Australia

Germany2 sites

  • Investigational Site Number : 2760001

    Essen, 45122

  • Investigational Site Number : 2760003

    Hanover, 30625

Other trials in Germany

Netherlands2 sites

  • Investigational Site Number : 5280001

    Rotterdam, 3015 GD

  • Investigational Site Number : 5280002

    Utrecht, 3584 CX

Other trials in Netherlands

South Korea2 sites

  • Investigational Site Number : 4100001

    Seoul, Seoul-teukbyeolsi, 03080

  • Investigational Site Number : 4100002

    Seoul, Seoul-teukbyeolsi, 138-736

Other trials in South Korea

United Kingdom2 sites

  • Investigational Site Number : 8260002

    Cardiff, Vale of Glamorgan, the, CF14 2TL

  • Investigational Site Number : 8260001

    Glasgow, Central Bedfordshire, G12 0YN

Other trials in United Kingdom

Belgium1 site

  • Investigational Site Number : 0560001

    Leuven, 3000

Other trials in Belgium

Estonia1 site

  • Investigational Site Number : 2330001

    Tallinn, 13419

Other trials in Estonia

Taiwan1 site

  • Investigational Site Number : 1580002

    Tainan, 704

Other trials in Taiwan

About this study

Official 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

Primary Objectives:

Dose escalation (Part 1)

Read more

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.
Read the 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.

Being tested
SAR439459, Cemiplimab REGN2810

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SAR439459Biological

    Pharmaceutical form: powder for solution for infusion

    Route of administration: intravenous infusion

  • Cemiplimab REGN2810Drug

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous infusion

Study groups in NCT03192345
Study groupRoleWhat they receive
Dose Escalation SAR439459 monotherapyExperimentalSAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses
Receives: Biological: SAR439459
Dose Expansion SAR439459 monotherapyExperimentalSAR439459 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
Receives: Biological: SAR439459
Dose Escalation SAR439459 + cemiplimab combinationExperimentalSAR439459 + 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
Receives: Biological: SAR439459; Drug: Cemiplimab REGN2810
Dose Expansion SAR439459 + cemiplimab combinationExperimentalSAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with previously determined SAR439459 doses and cemiplimab
Receives: Biological: SAR439459; Drug: Cemiplimab REGN2810

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose Limiting Toxicities (DLTs)

    Incidence of DLTs at Cycle 1 and/or 2 in Parts 1A and 1B.

    Measured: 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)

  2. 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).

    Measured: Continuous throughout study assessment (up to approximately 1 year)

Secondary outcomes (13)

  1. 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).

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  2. Progression free survival (PFS)

    The time from first investigational medicinal product (IMP) administration until objective tumor progression or death (Part 2A and Part 2B).

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  3. Time to progression (TTP)

    The time from first IMP administration until objective tumor progression (Part 2A and 2B).

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  4. 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).

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  5. Duration of response Part 2B

    Time from initial response to the first documented tumor progression.

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  6. Disease Control Rate Part 2B

    Sum of complete response, partial response and stable disease rates

    Measured: Continuous throughout study assessment (up to approximately 1 year)

  7. Immunogenicity evaluation

    Blood samples will be assessed for human anti-SAR439459 antibodies (all cohorts) and for human anti-cemiplimab antibodies (Parts 1B and 2B).

    Measured: Up to approximately 1 year

  8. Cmax for SAR439459 and for cemiplimab

    Maximum plasma concentration observed.

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

  9. AUC for SAR439459

    Area under the serum concentration versus time curve extrapolated to infinity.

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

  10. 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.

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

  11. t1/2z for SAR439459

    Terminal half-life associated with the terminal slope (λz).

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

  12. CL for SAR439459

    Total body clearance of a drug from plasma calculated using the following equation from AUC: CL= Dose/AUC on cycle 1.

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

  13. Vss for SAR439459

    Estimate of Volume of distribution at the steady state after single intravenous dose.

    Measured: Cycle 1, Day 1 to Day 15 or to Day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2017
  2. Study start9 Jun 2017
  3. Primary completion21 Dec 2021
  4. Study completion17 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Escalation monotherapy and escalation combination followed by expansion monotherapy and expansion combination. Escalation phases will not be randomized while expansion phases will be randomized.
Masking
None (open label)
Enrolment
161 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03192345
Sponsor's protocol ID
TCD14678
Other IDs
TCD14678, U1111-1187-5425, 2018-001113-32, 2018
Status last verified
Aug 2024
First submitted
16 Jun 2017
Last updated
7 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Baranda JC, Robbrecht D, Sullivan R, Doger B, Santoro A, Barve M, Grob JJ, Bechter O, Vieito M, de Miguel MJ, Schadendorf D, Johnson M, Pouzin C, Cantalloube C, Wang R, Lee J, Chen X, Demers B, Amrate A, Abbadessa G, Hodi FS. Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of SAR439459, a TGFbeta inhibitor, as monotherapy and in combination with cemiplimab in patients with advanced solid tumors: Findings from a phase 1/1b study. Clin Transl Sci. 2024 Jun;17(6):e13854. doi: 10.1111/cts.13854.

    PubMed 38898592

  • Greco R, Qu H, Qu H, Theilhaber J, Shapiro G, Gregory R, Winter C, Malkova N, Sun F, Jaworski J, Best A, Pao L, Hebert A, Levit M, Protopopov A, Pollard J, Bahjat K, Wiederschain D, Sharma S. Pan-TGFbeta inhibition by SAR439459 relieves immunosuppression and improves antitumor efficacy of PD-1 blockade. Oncoimmunology. 2020 Sep 13;9(1):1811605. doi: 10.1080/2162402X.2020.1811605.

    PubMed 33224628

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SAR439459 and Cemiplimab REGN2810 in people with Malignant Solid Tumor, run by Sanofi at 34 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Spain, France, Canada, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose Limiting Toxicities (DLTs) (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03192345, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.

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