Advanced solid tumors
Conditions
Interventions
SAR441000 is to be administered intratumorally once per week in a 4-week cycle
(ie, four doses every 28 days). After each cycle of treatment, the frequency of
intratumoral injection will continue we
Sponsors
Genzyme Europe BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For dose escalation phase (monotherapy and combination therapy): Subjects must have a diagnosis of Advanced solid tumors including lymphomas for which no standard alternative therapy is available For dose expansion phase (combination therapy): -Subjects must have a diagnosis of 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. Subjects must have a minimum of 3 lesions at enrollment and 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. Additional patients to be included at the end of escalation phase (monotherapy and combination therapy): Participants with histologically confirmed, advanced unresectable or metastatic solid tumors expected to be highly immunogenic (such as melanoma, HNSCC, SCC, or TNBC), who have previously progressed during treatment with anti-PD1/anti-PD-L1 therapies, and who either have already exhausted or declined all available SOCs or for whom there is a contraindication to available SOCs in the opinion of the Investigator.
Exclusion criteria
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. - 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. - Central nervous system lymphoma - Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with lymphoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Escalation monotherapy and combination therapy: Incidence of DLTs during first 28 days of treatment. - Expansion monotherapy and combination therapy: Objective response rate (ORR): efficacy as documented by ORR will be assessed by evaluation of anti-tumor response information according to RECIST 1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| -The overall safety profile of SAR441000 administered as monotherapy or in combination with cemiplimab. -To characterize the pharmacokinetic profile of the cytokines encoded by SAR441000 administered as monotherapy and in combination with cemiplimab. - PK profile of cemiplimab in combination with SAR441000. - Assess the immunogenicity of cytokines encoded by SAR441000 when administered as monotherapy and in combination with cemiplimab. * Disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) of SAR441000 in monotherapy and in combination with cemiplimab according to RECIST 1.1 and iRECIST criteria. To determine the recommended dose of SAR441000 as monotherapy and in combination with cemiplimab for the expansion phases. | — |
Countries
Netherlands
Outcome results
None listed