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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05839626




Registration number
NCT05839626
Ethics application status
Date submitted
31/03/2023
Date registered
3/05/2023
Date last updated
8/05/2024

Titles & IDs
Public title
A Study to Investigate Safety and Efficacy With SAR445514 in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and Relapsed/Refractory Light-chain Amyloidosis (RRLCA)
Scientific title
First-in-human, Open-label Phase 1/2 Study to Investigate Safety and Efficacy of SAR445514, an NKcell Engager (NKCE) Targeting B-cell Maturation Antigen (BCMA) in Monotherapy in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and in Relapsed/Refractory Light-chain Amyloidosis (RRLCA)
Secondary ID [1] 0 0
U1111-1279-2985
Secondary ID [2] 0 0
TCD17710
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple Myeloma 0 0
Amyloid Light-chain Amyloidosis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR445514

Experimental: SAR445514 RRMM Dose escalation phase (Part 1a) - SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

Experimental: SAR445514 RRLCA Dose escalation phase (part 1b) - SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA)) using subcutaneous route (SC)

Experimental: SAR445514 Dose level A (part 2) - SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

Experimental: SAR445514 Dose level B (part 2) - SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

Experimental: SAR445514 RRMM Dose expansion (part 3a) - SAR445514 will be administered to participants with relapsed/refractory multiple myeloma (RRMM) using subcutaneous route (SC)

Experimental: SAR445514 RRLCA Dose expansion (part 3b) - SAR445514 will be administered to participants with relapsed/refractory light chain amyloidosis (RRLCA) using subcutaneous route (SC)


Treatment: Drugs: SAR445514
Powder for solution for injection. Sub Cutaneous administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose escalation (part 1a - RRMM) Presence of dose limiting toxicities (DLT)
Timepoint [1] 0 0
Cycle 1 - 4 weeks per cycle
Primary outcome [2] 0 0
Dose escalation (part 1a - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Timepoint [2] 0 0
From Baseline to end of follow-up (approx. 15 months)
Primary outcome [3] 0 0
Dose optimization (part 2 - RRMM) Overall response rate (ORR)
Timepoint [3] 0 0
Cycles 1 to 4 - 4 weeks per cycle
Primary outcome [4] 0 0
Dose escalation (part 1b - RRLCA) Presence of dose limiting toxicities (DLT) at cycle 1
Timepoint [4] 0 0
Cycle 1 - 4 weeks per cycle
Primary outcome [5] 0 0
Dose escalation (part 1b - RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Timepoint [5] 0 0
From baseline to end of follow-up (approx. 15 months)
Primary outcome [6] 0 0
Dose expansion (part 3 - RRMM) Overall response rate (ORR)
Timepoint [6] 0 0
Cycles 1 to 4 - 4 weeks per cycle
Primary outcome [7] 0 0
Dose expansion (part 3-RRLCA) Hematological response (HR)
Timepoint [7] 0 0
Cycles 1 to 4 - 4 weeks per cycle
Secondary outcome [1] 0 0
Dose escalation (part 1 - RRMM) Overall response rate (ORR)
Timepoint [1] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [2] 0 0
Dose optimization (part 2 - RRMM) Presence of dose limiting toxicities (DLT)
Timepoint [2] 0 0
Cycles 1 to 4 - 4 weeks per cycle
Secondary outcome [3] 0 0
Dose optimization (part 2 - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Timepoint [3] 0 0
From first dose of study treatment up to 30 days after last dose of study treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [4] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Very Good Partial Response (VGPR) or Better Rate
Timepoint [4] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [5] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Duration of response (DOR)
Timepoint [5] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [6] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Time to first response (TT1R)
Timepoint [6] 0 0
Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days)
Secondary outcome [7] 0 0
Dose optimization & expansion (Part 2 & Part 3a -RRMM) Time to best response (TTBR)
Timepoint [7] 0 0
Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days)
Secondary outcome [8] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Progression free survival (PFS)
Timepoint [8] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [9] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Overall survival (OS)
Timepoint [9] 0 0
Cycle 1 to end of follow-up or death (approx. 15 months with cycle of 28 days)
Secondary outcome [10] 0 0
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Clinical benefit rate (CBR)
Timepoint [10] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [11] 0 0
Dose escalation (part 1b - RRLCA) Overall Hematological Response (OHR)
Timepoint [11] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [12] 0 0
Dose extension (part 3b - RRLCA) Hematological complete response rate (HCR).
Timepoint [12] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [13] 0 0
Dose extension (part 3b - RRLCA) Hematological very good partial response rate or better (HVGPR)
Timepoint [13] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [14] 0 0
Dose expansion (part 3b - RRLCA) Overall survival (OS)
Timepoint [14] 0 0
Cycle 1 to death or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [15] 0 0
Dose expansion (part 3b - RRLCA) Progression-Free Survival (PFS)
Timepoint [15] 0 0
Cycle 1 to first progressive disease (organ or hematological) or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [16] 0 0
Dose expansion (part 3b - RRLCA) Time to first hematological response (TT1HR)
Timepoint [16] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [17] 0 0
Dose expansion (part 3b - RRLCA) Duration of hematological response (DOHR)
Timepoint [17] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)
Secondary outcome [18] 0 0
Dose expansion (Part 3 - RRMM & RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Timepoint [18] 0 0
From first dose of study treatment up to 30 days after last dose of study treatment (approx. 15 months with cycle of 28 days)
Secondary outcome [19] 0 0
Incidence rate of infusion associated reactions (IARs)
Timepoint [19] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [20] 0 0
Incidence rate of injection site reactions (ISR)
Timepoint [20] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [21] 0 0
Incidence of laboratory abnormalities
Timepoint [21] 0 0
From cycle 1 to end of follow-up (approx. 15 months with cycle of 28 days)
Secondary outcome [22] 0 0
Assessment of pharmacokinetics (PK) parameter of SAR445514: Ctrough
Timepoint [22] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [23] 0 0
Assessment of pharmacokinetics (PK) parameter of SAR445514: AUClast
Timepoint [23] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [24] 0 0
Assessment of pharmacokinetics (PK) parameter of SAR445514: Cmax
Timepoint [24] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [25] 0 0
Assessment of pharmacokinetics (PK) parameter of SAR445514: Tmax
Timepoint [25] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [26] 0 0
Incidence of anti-drug antibody (ADA) against SAR445514
Timepoint [26] 0 0
From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days)
Secondary outcome [27] 0 0
Dose extension (Part 3 - RRMM & RRLCA) Minimum Residual Disease (MRD) negativity rate
Timepoint [27] 0 0
Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days)

Eligibility
Key inclusion criteria
Participants must have a documented diagnosis of multiple myeloma (Part 1a, 2, and 3a) or
light chain amyloidosis (Part 1b and 3b).

Participants with RRMM (Part 1, 2, and 3a)

- Participants with measurable disease for RRMM

- Participants with MM must have received at least 2 prior lines of therapy which must
include at least 2 consecutive cycles of a second or third generation immunomodulator,
steroid, proteasome inhibitor and anti-CD38 monoclonal antibody (MoAb).

- Participants must have documented evidence of progressive disease (PD), as per IMWG
2016 criteria.

Participants with RR LCA (Part 1b and 3b) must have received at least 1 prior line of
treatment comprising at least 1 proteasome inhibitor.

- Participants with measurable disease according to ISA 2012.

- Participants must have documented evidence of progressive disease (PD), as per ISA
2012 criteria.

- One or more organ impacted by amyloidosis as per National comprehensive cancer network
(NCCN) guidelines.

For dose escalation, body weight within 40 to 120 kg

Capable of giving signed informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

Medical conditions

- Primary refractory MM defined as participants who never achieved at least a minimal
response with any treatment during the disease course

- Second primary malignancy

Participants with RRMM (Part 1a, 2, and 3a)

- For MM participants, primary systemic LCA and plasma cell leukemia

- For MM participants, congestive heart failure (New York Heart Association [NYHA])
Grade =II; cardiomyopathy, active ischemia, or any other uncontrolled cardiac
condition

Participants with RR LCA (Part 1b and 3b)

- For LCA participants, evidence of clinically significant cardiovascular condition,
defined as one or more of the following:

1. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >8500 ng/mL

2. New York Heart Association (NYHA) classification III or IV heart failure

3. Heart failure that, in the opinion of the Investigator, is not primarily related
to LCA cardiomyopathy (including, but not limited to, ischemic heart disease,
uncorrected valvular disease, infections)

4. Prior event (history) in the last 6 months of acute coronary syndrome, myocardial
infarction or unstable angina as well as participants who during the last 6
months experienced a percutaneous cardiac intervention with stent and/or a
coronary artery bypass

5. Hospitalization in the last 4 weeks prior to treatment related to a
cardiovascular event

6. Participants with prior history of arrhythmia and/or cardiac conduction disorders
for which a pacemaker or an implantable cardioverter defibrillator (ICD) is
required but has not been placed. This includes, but may not be limited to,
sustained ventricular tachycardia, association of an atrioventricular, or
sinoatrial nodal dysfunction

- For LCA participants, a systolic blood pressure <100 mmHg or a diastolic blood
pressure <55 mmHg.

- For LCA participants: previous or current diagnosis of symptomatic MM, including the
presence of lytic bone disease, plasmacytomas, =60% plasma cells in the BM, or
hypercalcemia.

All participants

- Uncontrolled infection within 14 days prior to study treatment.

- Known acquired immunodeficiency syndrome-related illness or known human
immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis
A (defined as positive hepatitis A antigen or positive IgM); HIV serology at screening
will be tested for participants in countries where it is required by local
regulations.

- Uncontrolled or active hepatitis B virus (HBV) infection: participants with positive B
surface antigen (HBsAg) and/or HBV deoxyribonucleic acid (DNA)

- Active hepatitis C virus (HCV) infection: positive HCV ribonucleic acid (RNA) and
negative anti-HCV.

Prior/concomitant therapy

- Any anti-MM drug treatment within 14 days before study treatment

- Prior allogenic hematopoietic stem cell (HSC) transplant with active graft-versus-host
disease (GvHD) (GvHD any grade and/or being under immunosuppressive treatment within
the last 2 months prior to first IMP).

- Any major procedure within 14 days before the initiation of the study treatment

- Administration of an anti-CD38 monoclonal antibody (isatuximab or daratumumab) less
than 90 days prior to the first administration of study treatment.

- Administration of an anti-BCMA agent (including, but not limited to, CAR T-cells,
TCEs, antibody drug conjugate) less than 21 days prior to the administration of study
treatment.

- Unresolved toxicities from prior anticancer therapy, defined as not having resolved to
CTCAE Version 5.0 Grade 1, at the exception of residual Grade 2 peripheral
neurotoxicity related to bortezomib and/or thalidomide and considered as stable.

- Participants with a contraindication to dexamethasone.

Prior/concurrent clinical study experience

- Received any other investigational drugs or prohibited therapy for this study within
28 days or 5 half-lives from study treatment, whichever is shorter

Diagnostic assessments

- Hemoglobin <8 g/dL (5.0 mmol/L)

- Platelets <50 × 10^9/L (not permissible to transfuse a participant within 1 week prior
to the screening platelet count to reach this level).

- Absolute neutrophil count (ANC) <1000 µL (1 × 10^9/L).

- Creatinine clearance <30 mL/min (Modification of Diet in Renal Disease Formula).

- Total bilirubin >1.5 × upper limit of normal (ULN) (unless the subject has documented
Gilbert syndrome in which case direct bilirubin should not be >2.5 × ULN).

- Aspartate aminotransferase (AST/SGOT) or Alanine aminotransferase (ALT/SGPT) >2.5 ×
ULN.

- Participants with Grade 3 or 4 hypercalcemia (corrected serum calcium of >12.5 mg/dL;
>3.1 mmol/L; ionized calcium >1.6 mmol/L; or requiring hospitalization) will not be
eligible unless participants recover to Grade 2 or less under anti-hypercalcemia
treatment.

Other exclusions

- Individuals accommodated in an institution because of regulatory or legal order;
prisoners or participants who are legally institutionalized

- Participant not suitable for participation, whatever the reason, as judged by the
Investigator

- Sensitivity to any of the study interventions, or components thereof, or drug or other
allergy that, in the opinion of the Investigator, contraindicates participation in the
study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
11/08/2027
Actual
Sample size
Target
101
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360001 - Wollongong
Recruitment hospital [2] 0 0
Investigational Site Number : 0360002 - Richmond
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Anderlecht
Country [2] 0 0
Belgium
State/province [2] 0 0
Antwerpen
Country [3] 0 0
Czechia
State/province [3] 0 0
Ostrava - Poruba
Country [4] 0 0
Hungary
State/province [4] 0 0
Budapest
Country [5] 0 0
Italy
State/province [5] 0 0
Lombardia
Country [6] 0 0
Spain
State/province [6] 0 0
Cantabria
Country [7] 0 0
Spain
State/province [7] 0 0
Cataluña
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Birmingham
Country [10] 0 0
United Kingdom
State/province [10] 0 0
London
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human (FIH) Phase 1/Phase 2 study for evaluating SAR445514 in monotherapy
in participants with relapsed/refractory multiple myeloma (RRMM) and relapsed/refractory
light chain amyloidosis (RRLCA).

The study will comprise 3 parts:

A dose escalation phase (Part 1) in RRMM participants (Part 1a) that will evaluate several
doses administered to determine 2 doses that will be tested in the dose optimization part.

A dose escalation will also be done in RRLCA participants (Part 1b) but started sequentially
after the end of the dose escalation in RRMM participants. This dose escalation will evaluate
the 2 doses planned to be used in dose optimization in RRMM, to ensure those doses are safe
also for RRLCA participants.

A dose optimization phase (Part 2) that will be evaluating 2 doses determined from Part 1 to
determine the preliminary recommended Phase 2 dose (pRP2D) and schedule for SAR445514 in
RRMM.

A dose expansion phase (Part 3) that will evaluate the preliminary efficacy of pRP2D and
schedule for SAR445514 in RRMM (Part 3a) and RRLCA (Part 3b).

Approximately 101 participants will be enrolled and treated by study intervention and
separated as such:

Part 1a: Approximately 18 to 30 participants Part 1b: Approximately 6 to 12 participants Part
2: Approximately 30 participants Part 3a: Approximately 15 participants Part 3b:
Approximately 14 participants
Trial website
https://clinicaltrials.gov/ct2/show/NCT05839626
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
contact-us@sanofi.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05839626