A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

NCT ID: NCT03871348

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-03
• Study Completion Date: 2024-02-21

Brief Summary

Primary Objectives:

• Dose Escalation: To determine maximum tolerated dose (MTD) or maximum administered dose (MAD) and overall safety and tolerability profile of SAR441000 when administered intratumorally as monotherapy and in combination with cemiplimab in patients who have no alternative standard treatment options.
• Dose Expansion (Combination): To determine the objective response rate of SAR441000 administered intratumorally in combination with cemiplimab in patients with melanoma, cutaneous squamous cell carcinoma or head and neck squamous cell carcinoma.

Secondary Objectives:

• To characterize the pharmacokinetic (PK) profile of SAR441000 administered as monotherapy and in combination with cemiplimab.
• To assess the immunogenicity of SAR441000.
• To characterize the safety of SAR441000 when administered intratumorally in combination with cemiplimab.
• To determine the disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) of SAR441000.
• To determine the recommended dose of SAR441000 for the expansion phase.

Detailed Description

The expected duration of treatment for patients who benefit from study intervention may vary, based on progression date. Median expected duration of study per patient is estimated as 9 months in monotherapy and 12 months in combination therapy.

The maximum treatment duration for non-progressive patients is up to 2 years.

Conditions

Metastatic Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR441000 Dose Escalation Phase

SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

SAR441000 + cemiplimab - Dose Escalation Phase

SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for injection

Route of administration: intravenous

SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced melanoma who have failed anti-PD-1/PD-L1 therapy. Treatment is administered over a 21-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for injection

Route of administration: intravenous

SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve melanoma over a 21-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for injection

Route of administration: intravenous

SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Cutaneous Squamous Cell Carcinoma (CSCC) over a 21-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for injection

Route of administration: intravenous

SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Head and Neck Squamous Cell Cancer (HNSCC) over a 21-day cycle

Group Type: EXPERIMENTAL

SAR441000

Intervention Type: DRUG

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for injection

Route of administration: intravenous

Interventions

SAR441000

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

Intervention Type: DRUG

Cemiplimab REGN2810

Pharmaceutical form: solution for injection

Route of administration: intravenous

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• At least 18 years of age
• Advanced solid tumors including lymphomas for which no standard alternative therapy is available (escalation phase).
• Advanced melanoma (Stage IIIB-C or Stage IV, anti-PD-1/PD-L1 treated or not) or anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer or anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer where no other alternative treatment option exists (expansion phases).
• Minimum 3 lesions enrollment.
• Injectable disease (i.e., suitable for direct intratumoral injection based on the dose level volume of each cohort and cumulative lesion size; according to the investigator's judgement).
• A lesion amenable for additional tumor biopsy.
• Patients with measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Life expectancy more than 3 months.
• Willingness to provide mandatory tumor biopsy.
• Male and female patients who agree to use effective contraceptive methods.
• Signed informed consent.

Exclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance score >1.
• Significant and uncontrolled concomitant illness that would adversely affect the patient's participation in the study.
• Any prior organ transplantation.
• History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected basal or squamous-cell skin cancer or carcinoma, in situ of cervix or other local tumors considered cured by local treatment.
• History of unresolved viral hepatitis; systemic immune suppression including acquired immunodeficiency syndrome (AIDS) related illnesses or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.
• Prior splenectomy.
• New and progressive brain lesions.
• Poor bone marrow reserve resulting in low blood cell count.
• Poor liver and kidney functions, abnormal coagulation tests.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
• Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent during the study.
• Non-resolution of any prior treatment related toxicity to Grade <2, except alopecia, vitiligo, fatigue and hypothyroidism controlled with replacement therapies.
• Moderate to severe immune related adverse event to prior immune-modulating agents within 90 days prior to the first study treatment.
• Central nervous system lymphoma.
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with lymphoma.
• Autologous HSCT less than 90 days prior to initiation of study intervention.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioNTech RNA Pharmaceuticals GmbH

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Dana-Farber Cancer Institute- Site Number : 8400003

Boston, Massachusetts, United States

Cleveland Clinic - Cleveland- Site Number : 8400007

Cleveland, Ohio, United States

The University of Texas MD Anderson Cancer Center- Site Number : 8400002

Houston, Texas, United States

Investigational Site Number : 0560001

Brussels, , Belgium

Investigational Site Number : 0560003

Ghent, , Belgium

Investigational Site Number : 0560002

Leuven, , Belgium

Investigational Site Number : 2500004

Marseille, , France

Investigational Site Number : 2500002

Paris, , France

Investigational Site Number : 2500001

Villejuif, , France

Investigational Site Number : 2760005

Hamburg, , Germany

Investigational Site Number : 2760004

Heidelberg, , Germany

Investigational Site Number : 2760001

Mainz, , Germany

Investigational Site Number : 2760003

Mannheim, , Germany

Investigational Site Number : 2760006

Tübingen, , Germany

Investigational Site Number : 5280002

Nijmegen, , Netherlands

Investigational Site Number : 5280001

Rotterdam, , Netherlands

Investigational Site Number : 7240004

Barcelona, Catalunya [Cataluña], Spain

Investigational Site Number : 7240001

Pamplona, Navarre, Spain

Investigational Site Number : 7240002

Valencia, , Spain

Countries

United States; Belgium; France; Germany; Netherlands; Spain

References

Bechter O, Loquai C, Champiat S, Baurain JF, Grob JJ, Utikal J, Rottey S, Berrocal A, Hassel JC, Arance A, Sanmamed MF, Boers-Sonderen M, Gastman B, Gebhardt C, Delafontaine B, Sahin U, Tureci O, Brueck P, Abbadessa G, Marpadga R, Lee H, Yang Y, Buday B, Di Genova G, Wang H, Xia B, Lee JS, Lebbe C. A Phase I, First-in-Human, Dose-Escalation, Expansion Trial of Cytokine-Encoding Synthetic mRNA Mixture Alone or with Cemiplimab in Advanced Solid Tumors. Clin Cancer Res. 2025 Jun 13;31(12):2358-2369. doi: 10.1158/1078-0432.CCR-24-1983.

Reference Type: RESULT

PMID: 40152791 (View on PubMed)

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25356&tenant=MT_SNY_9011

TED15297 Plain Language Results Summary

Other Identifiers

U1111-1205-1176

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-004766-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TED15297

Identifier Type: -

Identifier Source: org_study_id