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A Study to Investigate Safety and Efficacy With SAR445514 in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) and Relapsed/Refractory Light-chain Amyloidosis (RRLCA)
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 111 participants will be enrolled and treated by study intervention and separated as such: Part 1a: Approximately 30 to 40 participants Part 1b: Approximately 6 to 12 participants Part 2: Approximately 30 participants Part 3a: Approximately 15 participants Part 3b: Approximately 14 participants.
Study details:
The duration of the study for a participant will include A screening period: up to 28 days prior day 1 of cycle 1 (C1D1) A treatment period: enrolled participants will receive administration of 4 weeks cycles of SAR445514 subcutaneously. The End of treatment visit will occur 30 days (+/- 7 days) from last investigational medicinal product (IMP) administration or prior initiation of further therapy, whichever comes first. The follow-up period will continue until death, participant's request to discontinue study, final Overall Survival analysis or upon cancellation of survival follow-up at the discretion of the Sponsor at any timepoint.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2023-05-15
Primary completion: 2027-03-21
Study completion finish: 2028-04-07
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT05839626
Intervention or treatment
DRUG: SAR445514
Conditions
- • Relapsed/Refractory Multiple Myeloma
- • Amyloid Light-chain Amyloidosis
Find a site
Closest Location:
Investigational Site Number : 0360001
Research sites nearby
Select from list below to view details:
Investigational Site Number : 0360001
Wollongong, New South Wales, Australia
Investigational Site Number : 0360002
Richmond, Victoria, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: SAR445514 RRMM Dose escalation phase (Part 1a)
| DRUG: SAR445514
|
EXPERIMENTAL: SAR445514 RRLCA Dose escalation phase (part 1b)
| DRUG: SAR445514
|
EXPERIMENTAL: SAR445514 Dose level A (part 2)
| DRUG: SAR445514
|
EXPERIMENTAL: SAR445514 Dose level B (part 2)
| DRUG: SAR445514
|
EXPERIMENTAL: SAR445514 RRMM Dose expansion (part 3a)
| DRUG: SAR445514
|
EXPERIMENTAL: SAR445514 RRLCA Dose expansion (part 3b)
| DRUG: SAR445514
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Dose escalation (part 1a - RRMM) Presence of dose limiting toxicities (DLT) | DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or ICANS. | Cycle 1 - 4 weeks per cycle |
Dose escalation (part 1a - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs) | Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading | From Baseline to end of follow-up (approx. 15 months) |
Dose optimization (part 2 - RRMM) Overall response rate (ORR) | ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria, after the last participant is treated for at least 4 cycles or prematurely discontinued. | Cycles 1 to 4 - 4 weeks per cycle |
Dose escalation (part 1b - RRLCA) Presence of dose limiting toxicities (DLT) at cycle 1 | Not Specified | Cycle 1 - 4 weeks per cycle |
Dose escalation (part 1b - RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs) | Not Specified | From baseline to end of follow-up (approx. 15 months) |
Dose expansion (part 3 - RRMM) Overall response rate (ORR) | ORR is defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria. | Cycles 1 to 4 - 4 weeks per cycle |
Dose expansion (part 3-RRLCA) Hematological response (HR) | HR is defined as the proportion of participants with sCR, CR, VGPR, and PR according to the European society of hematology/International society of hematology working group guidelines. | Cycles 1 to 4 - 4 weeks per cycle |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Dose escalation (part 1 - RRMM) Overall response rate (ORR) | ORR defined as the proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose optimization (part 2 - RRMM) Presence of dose limiting toxicities (DLT) | Not Specified | Cycles 1 to 4 - 4 weeks per cycle |
Dose optimization (part 2 - RRMM) Percentage of participants experiencing treatment-emergent adverse events (TEAEs) | Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment. | From first dose of study treatment up to 30 days after last dose of study treatment (approx. 1 year with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Very Good Partial Response (VGPR) or Better Rate | VGPR is defined as the proportion of participants with sCR, CR, and VGPR according to the 2016 IMWG criteria. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Duration of response (DOR) | DOR is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Time to first response (TT1R) | TT1R is defined as the time from the date of the first response to the date of the first occurrence of progressive disease (PD as determined by the investigator or death from any cause, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). | Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a -RRMM) Time to best response (TTBR) | TTBR is defined as the time from the first administration of the IMP to the date of first occurrence of best overall response (PR or better that is subsequently confirmed. | Cycle 1 to first progressive disease or end of treatment whichever comes first (approx. 1 year with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Progression free survival (PFS) | PFS is defined as the time from the date of the first administration of the IMP to the date of first documentation of progressive disease or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Overall survival (OS) | OS is defined as the time from the date of the first administration of the IMP to death from any cause | Cycle 1 to end of follow-up or death (approx. 15 months with cycle of 28 days) |
Dose optimization & expansion (Part 2 & Part 3a - RRMM) Clinical benefit rate (CBR) | CBR is the rate of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months from the first IMP administration determined by the Investigator per IMWG 2016 criteria. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose escalation (part 1b - RRLCA) Overall Hematological Response (OHR) | OHR is defined as the proportion of participants with CR, VGPR, and PR according to the International Society of Amyloidosis guidelines (ISA 2012). | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose extension (part 3b - RRLCA) Hematological complete response rate (HCR). | HCR is defined as the proportion of participants with complete response according to the ISA 2012. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose extension (part 3b - RRLCA) Hematological very good partial response rate or better (HVGPR) | HVGPR defined as proportion of participants with very good partial response and CR as per ISA 2012 criteria | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose expansion (part 3b - RRLCA) Overall survival (OS) | OS is defined as the time from the date of study entry to death from any cause. | Cycle 1 to death or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose expansion (part 3b - RRLCA) Progression-Free Survival (PFS) | PFS is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause. | 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) |
Dose expansion (part 3b - RRLCA) Time to first hematological response (TT1HR) | TT1HR is defined as the time from the first administration of the IMP to the date of first hematological response (PR or better) that is subsequently confirmed. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose expansion (part 3b - RRLCA) Duration of hematological response (DOHR) | DOHR is defined as time from the time from the first administration of the IMP to any of the following: hematological progression, major organ progression (cardiac, kidney or liver) according to ISA 2012 criteria or death by any cause. | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
Dose expansion (Part 3 - RRMM & RRLCA) Percentage of participants experiencing treatment-emergent adverse events (TEAEs) | Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen, or become serious during the treatment-emergent period. | From first dose of study treatment up to 30 days after last dose of study treatment (approx. 15 months with cycle of 28 days) |
Incidence rate of infusion associated reactions (IARs) | Not Specified | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Incidence rate of injection site reactions (ISR) | Not Specified | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Incidence of laboratory abnormalities | Not Specified | From cycle 1 to end of follow-up (approx. 15 months with cycle of 28 days) |
Assessment of pharmacokinetics (PK) parameter of SAR445514: Ctrough | Not Specified | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Assessment of pharmacokinetics (PK) parameter of SAR445514: AUClast | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Assessment of pharmacokinetics (PK) parameter of SAR445514: Cmax | Maximum observed concentration | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Assessment of pharmacokinetics (PK) parameter of SAR445514: Tmax | First time to reach Cmax | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Incidence of anti-drug antibody (ADA) against SAR445514 | Not Specified | From cycle 1 to end of treatment (approx. 1 year with cycle of 28 days) |
Dose extension (Part 3 - RRMM & RRLCA) Minimum Residual Disease (MRD) negativity rate | MRD status in participants with response of VGPR or better | Cycle 1 to first progressive disease or end of follow-up whichever comes first (approx. 15 months with cycle of 28 days) |
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