Primary Objectives: Dose Escalation (SAR441000 Monotherapy): -To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the overall safety and tolerability profile of SAR441000 when administered intratumorally as…
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Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- 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 outcome
-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.
Background summary
Despite the multitude of immune therapeutics currently available for the
treatment of advanced melanoma, the overall response rates evaluated so far in
large clinical trials are moderate. As more patients are being treated with
checkpoint blocking agents* multiple cases of acquired resistance have been
reported, indicating a clear need to further develop highly specific,
well-tolerated, and efficient treatments for melanoma cancer patients. Melanoma
was chosen as an initial indication for SAR441000 since this cancer has been
previously shown to be responsive to recombinant cytokine therapy. Individual
cytokines (such as IFN*, GM-CSF, IL-12, or IL-15) are also being evaluated in
cancer patients as non-viral gene therapy or recombinant proteins which are
administered through different routes (intratumorally, intravenous [IV],
subcutaneous [SQ], local electroporation) and are being investigated alone and
in combination with checkpoint inhibitors. In pre-clinical in vivo studies,
SAR441000 encoded cytokines were observed not only in the tumor
microenvironment but also in the circulatory system; this may result in
stimulation of anti-tumor immune responses.
This study is a Phase I first-in-human, dose escalation, and dose expansion
study for the evaluation of safety, PK, PD, and anti-tumor activity of
SAR441000 administered intratumorally as monotherapy and in combination with
cemiplimab in adult patients with advanced solid tumors.
Study objective
Primary Objectives: Dose Escalation (SAR441000 Monotherapy): -To determine the
maximum tolerated dose (MTD) or maximum administered dose (MAD) and the overall
safety and tolerability profile of SAR441000 when administered intratumorally
as monotherapy in patients with advanced solid tumors who have failed prior
anti-PD-1 or anti-PD-L1 based therapy. Dose Escalation (Combination therapy):
To determine the maximum tolerated dose (MTD) or maximum administered dose
(MAD) and the overall safety and tolerability profile of SAR441000 when
administered weekly intratumorally in combination with a fixed dose of
cemiplimab 350 mg administered intravenously in patients with advanced solid
tumors. Dose Expansion (Combination therapy): -To determine the objective
response rate of SAR441000 administered intratumorally in combination with a
fixed dose of cemiplimab 350 mg administered intravenously in patients with
melanoma, cutaneous squamous cell carcinoma (CSCC), or head and neck squamous
cell carcinoma (HNSCC).
Secondary Objectives: Dose Escalation (Monotherapy and Combination therapy) and
expansion (combinationtherapy): -To characterize the PK profile of the
cytokines encoded by SAR441000 administered as monotherapy and in combination
with cemiplimab. -To characterize the PK profile of cemiplimab in combination
with SAR441000. -To assess the immunogenicity of cytokines encoded by SAR441000
when administered as monotherapy and in combination with cemiplimab. -To assess
immunogenicity of cemiplimab in combination therapy. -To characterize the
safety of SAR441000 when administered intratumorally as monotherapy in patients
with advanced melanoma and as a combination treatment with cemiplimab in HNSCC,
CSCC, and melanoma. - To determine the disease control rate (DCR), duration of
response (DoR) and progression free survival (PFS) of SAR441000 in monotherapy
and in combination with cemiplimab. -To determine the recommended dose of
SAR441000 as monotherapy and in combination with cemiplimab for the expansion
phases.
Study design
-Phase 1, open-label, parallel study. -Escalation monotherapy and combination
therapy followed by expansion combination therapy. Randomization is not
applicable in this study.
Intervention
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 weekly. However, during the conduct of the
study, the Study Committee may decide to reduce the dose administration
frequency to twice or once a month based on tumor burden decrease, which may
interfere with administration of the intended dose. Cemiplimab is to be
administered intravenously over 30 minutes every three weeks.
Study burden and risks
The risks are related to possible side effects by and/ or the administration of
study medication and the blood samples collection. The burden on the patient
will be the frequency of visits to the research center.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201700476694-NL |
| CCMO | NL71496.000.19 |
| Other | U1111-1205-1176 |