A Phase 1 first- in-human dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of SAR441000 administered intratumorally as monotherapy and in combination with cemiplimab in patients with advanced solid tumors

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 11

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

- 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Escalation monotherapy and combination therapy: Incidence of DLTs during<br /><br>first 28 days of treatment. - Expansion monotherapy and<br /><br>combination therapy: Objective response rate (ORR): efficacy as documented by<br /><br>ORR will be assessed by evaluation of anti-tumor response information according<br /><br>to RECIST 1.1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>-The overall safety profile of SAR441000 administered as monotherapy or in<br /><br>combination with cemiplimab. -To characterize the pharmacokinetic profile of<br /><br>the cytokines encoded by SAR441000 administered as monotherapy and in<br /><br>combination with cemiplimab. - PK profile of cemiplimab in combination with<br /><br>SAR441000. - Assess the immunogenicity of cytokines encoded by SAR441000 when<br /><br>administered as monotherapy and in combination with cemiplimab. * Disease<br /><br>control rate (DCR), duration of response (DoR) and progression free survival<br /><br>(PFS) of SAR441000 in monotherapy and in combination with cemiplimab according<br /><br>to RECIST 1.1 and iRECIST criteria. To determine the recommended dose of<br /><br>SAR441000 as monotherapy and in combination with cemiplimab for the expansion<br /><br>phases. </p><br>