An open-label, first-in-human, single agent, dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics and antitumor activity of SAR442085 in patients with relapsed or refractory multiple myeloma (RRMM)
Trial Description
Primary Objectives:
- Dose Escalation Part A: To determine the maximum tolerated dose (MTD) of SAR442085
administered as a single agent in patients with relapsed or refractory multiple
myeloma (RRMM), and determine the recommended Phase 2 dose (RP2D) for the subsequent
Expansion Part B
- Dose Expansion Part B: To assess the antitumor activity of single agent of SAR442085
at the RP2D in patients with RRMM
Secondary Objectives:
- To characterize the safety profile of SAR442085
- To characterize the pharmacokinetics (PK) profile of SAR442085 when administered as
a single agent
- To evaluate the potential immunogenicity of SAR442085
- To assess preliminary evidence of antitumor activity in the Dose Escalation Part A
Eligibility Requirements
Inclusion criteria :
- Participant must be at least 18 years of age or of the country's legal age of
majority if the legal age is >18 years old, at the time of signing the informed
consent.
- Participant has given voluntary written informed consent.
- Participant has been previousy diagnosed with multiple myeloma based on standard
criteria.
- Part A: (1) participant has received at least 3 prior lines of therapy for multiple
myeloma, or at least 2 prior lines of therapy if at least 1 of those lines consisted
of 2 or more multi-agent regimens (eg, multi-agent induction regimen with autologous
stem cell transplantation, followed by maintenance regimen). (2) Prior therapy for
multiple myeloma has included at least 1 proteasome inhibitor (bortezomib,
carfilzomib, ixazomib), at least 1 immunomodulatory agent (lenalidomide,
thalidomide, pomalidomide), at least 1 anti-CD38 monoclonal antibody and at least 1
steroid. Applicable countries in EU and Asia can enroll anti-CD38 naive RRMM
patients from DL4 and onwards. (3) Participant had at least a minimal response (MR)
to the anti-CD38 antibody containing regimen and had last dose of anti-CD38
monoclonal antibody at least 9 months prior to study entry. Applicable countries in
EU and Asia can enroll anti-CD38 naive RRMM patients from DL4 and onwards.
- Part B and the last cohort(s) of Part A: (1) participant has received at least 3
prior lines of therapy for multiple myeloma, or at least 2 prior line of therapy if
at least 1 of those lines consisted of 2 or more multi-agent regimens (eg,
multi-agent induction regimen with autologous stem cell transplantation, followed by
maintenance regimen). (2) Prior therapy for multiple myeloma has included at least 1
proteasome inhibitor (bortezomib, carfilzomib, ixazomib), at least 1
immunomodulatory agent (lenalidomide, thalidomide, pomalidomide) and at least 1
steroid. (3) Prior therapy has not included an anti-CD38 monoclonal antibody.
- Participant has myeloma disease progression on or after last therapy.
- Participant must have measurable disease as defined as at least one of the
following:
- Serum M protein ≥0.5 g/dL (≥5 g/L)
- Urine M protein ≥200 mg/24 hours
- Serum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum
- FLC ratio (<0.26 or >1.65).
- A male participant must agree to use contraception during the intervention period
and for at least 150 days after the last dose of study drug and refrain from
donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- A WOCBP who agrees to follow the contraceptive guidance during the intervention
period and for at least 150 days after the last dose of study intervention.
Exclusion criteria:
- Participant is diagnosed or treated for another malignancy within 3 years prior to
enrollment, with the exception of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, superficial bladder carcinoma or low risk prostate
cancer.
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status
score >2.
- Participant has a history of Chronic obstructive pulmonary disease (COPD) or asthma.
- Participant has not recovered from adverse reactions to prior myeloma treatment or
procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE Grade ≤1 or
baseline (exception: alopecia).
- Participant has congestive heart failure (New York Heart Association) Grade ≥II;
cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such
as angina pectoris, clinically significant arrhythmia requiring therapy including
anticoagulants, or clinically significant uncontrolled hypertension, QT interval
corrected by the Fridericia method >480 msec (Grade ≥2).
- Participant has had acute myocardial infarction within 6 months before first dose of
study medication.
- Participant has ongoing sensory or motor neuropathy of National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥3.
- Participant has active autoimmune disease including autoimmune hemolytic anemia,
idiopathic thrombocytopenic purpura, inflammatory bowel syndrome, pneumonitis or any
chronic condition requiring a higher corticosteroid systemic equivalent than
prednisone 10 mg daily.
- Known acquired immunodeficiency syndrome (AIDS) or related illnesses or human
immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or to have
active hepatitis A, B (defined as a known positive hepatitis B surface antigen
(HBsAg) result or positive HepB DNA), or C (defined as a known quantitative
hepatitis C [HCV] ribonucleic acid RNA results greater than the lower limits of
detection of the assay or positive HCV antigen) infection.
- Participant has positive Coombs test at baseline.
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.