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

NCT03871348 | Terminated Phase 1 FDA Drug

• 3 other identifiers: TED15297U1111-1205-11762017-004766-94
• Study Type: interventional
• Target: 77
• Locations: 6 countries
• Sites: 19

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.

Conditions

Metastatic Neoplasm

Outcome Measures

Primary Outcomes (6)

• For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Monotherapy)

  Incidence of DLTs at Cycle 1 (SAR441000 monotherapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression

  Cycle 1; Cycle = 28 days for monotherapy

• For dose escalation: Incidence of Dose Limiting Toxicities (DLTs) (Combination therapy)

  Incidence of DLTs during period from Cycle 1 Day 1 to Cycle 2 Day 8 (SAR441000 + cemiplimab combination therapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using NCI-CTCAE version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression

  Cycle 1 Day 1 to Cycle 2 Day 8; Cycle = 21 days for combination therapy; overall assessment = 28 days

• For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Monotherapy)

  MTD of SAR441000 as monotherapy, determined during Cycle 1 of dose escalation phase

  End of Dose Escalation phase (ie, End of Cycle 1 for last patient); Cycle = 28 days for monotherapy

• For dose escalation: Maximum tolerated dose (MTD) of SAR441000 (Combination therapy)

  MTD of SAR441000, in combination with cemiplimab, determined during period from Cycle 1 Day 1 to Cycle 2 Day 8 in dose escalation phase

  End of Dose Escalation Phase (ie, End of Cycle 1 Day 1 to Cycle 2 Day 8 for last patient); Cycle = 21 days for combination; overall assesment = 28 days

• Adverse Events

  Incidence of Treatment Emergent Adverse Events (TEAE) during dose escalation phase

  Up to end of treatment (Estimated median duration=12 months)

• For Expansion: Objective Response Rate (ORR)

  Assessment of overall response rate using standard imaging and RECIST 1.1 criteria

  Estimated median duration = 12 months

Secondary Outcomes (15)

• Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Monotherapy)

  Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy

• Assessment of Pharmacokinetic (PK) parameter for SAR441000 (Cmax) (Combination therapy)

  Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy

• Assessment of PK parameter for SAR441000 (AUC) (Monotherapy)

  Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 28 days for monotherapy

• Assessment of PK parameter for SAR441000 (AUC) (Combination therapy)

  Cycle 1 Week 1 and Cycle 3 Week 1 (in all patients); Cycle duration is 21 days for combination therapy

• Assessment of PK parameter (Ctrough) for SAR441000

  Baseline to End of Treatment (Estimated median duration of 12 months)

Study Arms (6)

SAR441000 Dose Escalation Phase

EXPERIMENTAL

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

Drug: SAR441000

SAR441000 + cemiplimab - Dose Escalation Phase

EXPERIMENTAL

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

Drug: SAR441000; Drug: Cemiplimab REGN2810

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

EXPERIMENTAL

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

Drug: SAR441000; Drug: Cemiplimab REGN2810

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

EXPERIMENTAL

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

Drug: SAR441000; Drug: Cemiplimab REGN2810

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

EXPERIMENTAL

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

Drug: SAR441000; Drug: Cemiplimab REGN2810

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

EXPERIMENTAL

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

Drug: SAR441000; Drug: Cemiplimab REGN2810

Interventions

SAR441000 DRUG

Pharmaceutical form: concentrate for solution for injection Route of administration: intratumoral

SAR441000 + cemiplimab - Dose Escalation Phase; SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive; SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive; SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure; SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive; SAR441000 Dose Escalation Phase

Cemiplimab REGN2810 DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous

SAR441000 + cemiplimab - Dose Escalation Phase; SAR441000 + cemiplimab Expansion CSCC, anti-PD-1 naive; SAR441000 + cemiplimab Expansion HNSCC, anti-PD-1 naive; SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 failure; SAR441000 + cemiplimab Expansion Melanoma, anti-PD-1 naive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• BioNTech RNA Pharmaceuticals GmbH: collaborator

Study Sites (19)

Dana-Farber Cancer Institute- Site Number : 8400003

Boston, Massachusetts, 02215, United States

Location

Cleveland Clinic - Cleveland- Site Number : 8400007

Cleveland, Ohio, 44195, United States

Location

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

Houston, Texas, 77030, United States

Location

Investigational Site Number : 0560001

Brussels, 1200, Belgium

Location

Investigational Site Number : 0560003

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560002

Leuven, 3000, Belgium

Location

Investigational Site Number : 2500004

Marseille, 13885, France

Location

Investigational Site Number : 2500002

Paris, 75010, France

Location

Investigational Site Number : 2500001

Villejuif, 94805, France

Location

Investigational Site Number : 2760005

Hamburg, 20246, Germany

Location

Investigational Site Number : 2760004

Heidelberg, 69120, Germany

Location

Investigational Site Number : 2760001

Mainz, 55131, Germany

Location

Investigational Site Number : 2760003

Mannheim, 68167, Germany

Location

Investigational Site Number : 2760006

Tübingen, 72076, Germany

Location

Investigational Site Number : 5280002

Nijmegen, 6525 GA, Netherlands

Location

Investigational Site Number : 5280001

Rotterdam, 3015 CE, Netherlands

Location

Investigational Site Number : 7240004

Barcelona, Catalunya [Cataluña], 08036, Spain

Location

Investigational Site Number : 7240001

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 7240002

Valencia, 46014, Spain

Location

Related Publications (1)

• 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.

  PMID: 40152791 RESULT

Related Links

• TED15297 Plain Language Results Summary

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: March 12, 2019
• Study Start: January 3, 2019
• Primary Completion: July 25, 2022
• Study Completion: February 21, 2024
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); NL (2); ES (3); US (3); BE (3); FR (3)