Isatuximab in combination with SAR445761 (belumosudil) and dexamethasone in relapsed or refractory multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Mar 2021 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-514992-16-00

EudraCT number

2020-003024-16

WHO UTN

U1111-1310-0675

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacodynamic, Pharmacokinetic

• Part 1 (dose finding, experimental substudies):
-To determine or confirm the recommended dose of novel agents when combined with isatuximab with or without dexamethasone in participants with RRMM.
• Part 2 (expansion, independent experimental substudies):
-To demonstrate the clinical benefit of novel agents combined with isatuximab with or without dexamethasone in terms of overall response rate (ORR).

Secondary objectives 12

1. To assess ORR in each treatment arm -ORR in Part 1 (dose finding, experimental substudies)
2. VGPR in Part 1 (dose finding, experimental substudies) and Part 2 (expansion, independent experimental substudies).
3. To assess the clinical benefit rate (CBR) in each treatment arm.
4. To assess the duration of response (DOR) in each treatment arm
5. To assess the time to first response (TT1R) in each treatment arm
6. To assess the time to best response (TTBR) in each treatment arm
7. To assess safety and tolerability in each treatment arm.
8. To assess progression free survival (PFS) in each treatment arm.
9. To assess overall survival (OS) in each treatment arm.
10. To evaluate the potential immunogenicity of isatuximab and novel agents when applicable.
11. To characterize the PK of isatuximab and novel agents
12. To assess disease and treatment related symptoms, cancer and disease specific health-related quality of life, global impact of side effects and confirm/establish clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores - Part 1 (dose optimization, independent experimental substudies) and Part 2 (expansion, independent experimental substudies).

Conditions and MedDRA coding

Cancer

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002205-PIP01-17

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be 18 years of age inclusive or older.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
3. Participants with relapsed or refractory MM who have received at least 2 prior lines of therapy for MM, including PIs and IMiDs (eg, Induction regimen with autologous stem cell transplant followed by maintenance is considered one line)
4. RRMM with measurable disease: Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
5. RRMM with measurable disease: Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
6. RRMM with measurable disease: Serum free light chain (sFLC) MM without measurable M protein in serum or urine per previous criteria (serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio <0.26 or >1.65)
7. Men or woman or childbearing potential should agree to use contraception
8. Substudy 05: Participants with RRMM with at least 1 cycle of prior exposure to anti- CD38 therapy. For participants to whom BCMA targeted therapy is available (ie, approved in their region and can be reimbursed), at least 2 cycles of prior exposure to a BCMA targeted agent is mandatory

Exclusion criteria 20

1. Primary systemic amyloid light chain amyloidosis, plasma cell leukemia, monoclonal gammopathy of undetermined significance, or smoldering myeloma.
2. Uncontrolled infection within 14 days prior to first study intervention administration.
3. Clinically significant cardiac (including valvular) or vascular disease within 3 months prior to first study intervention administration., eg, myocardial infarction, unstable angina, coronary (eg, coronary artery bypass graft, percutaneous coronary intervention) or peripheral artery revascularization, left ventricular ejection fraction <40%, heart failure New York Heart Association Classes III and IV, stroke, transient ischemic attack, pulmonary embolism, other thromboembolic event, or cardiac arrhythmia (Grade 3 or higher by NCI CTCAE Version 5.0).
4. Known acquired immunodeficiency syndrome-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A.
5. Uncontrolled or active hepatitis B virus (HBV) infection.
6. Active hepatitis C virus (HCV) infection.
7. Any of the following within 3 months prior to first study intervention administration: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease.
8. Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before first study intervention administration.
9. Any anti-MM drug treatment within 14 days before first study intervention administration, including dexamethasone.
10. Participants with a contraindication to treatment.
11. Vaccination with a live vaccine 4 weeks before the start of the study.
12. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
13. Hemoglobin <8 g/dL.
14. Platelets <50 × 10^9/L.
15. Absolute neutrophil count <1.0 × 10^9/L.
16. Creatinine clearance <30 mL/min/1.73m2.
17. Total bilirubin >1.5 × ULN, except for known Gilbert syndrome in which direct bilirubin should be ≤2.5 × ULN.
18. Aspartate aminotransferase and/or alanine aminotransferase >3 × ULN.
19. Patients with grade 3 or 4 hypercalcemia
20. Substudy 05:Unable to swallow tablets.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 (dose finding, experimental substudies): Determination of recommended dose of novel agents in combination with isatuximab
2. Part 2 (expansion, independent experimental substudies):Overall Response Rate (ORR) in independent experimental substudies

Secondary endpoints 19

1. Part 1 (dose finding, experimental substudies): ORR
2. Part 1 (dose finding, experimental substudies): VGPR or better
3. Part 2 (expansion, independent experimental substudies): VGPR or better
4. Clinical Benefit Rate (CBR) in each treatment arm
5. Duration of Response (DOR) in each treatment arm
6. Time to First Response (TT1R) in each treatment arm
7. Time to Best Response (TTBR) in each treatment arm
8. Number of participants with treatment emergent adverse events and serious adverse events in each treatment arm
9. Progression-free survival (PFS) in each treatment arm
10. Overall Survival (OS) in each treatment arm
11. Immunogenicity of isatuximab and novel agents
12. Concentration of novel agents (experimental arms) and isatuximab (Ctrough)
13. Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
14. Disease- and treatment-related quality of life will be assessed using the EORTC multiple myeloma module (QLQ-MY20) questionnaire
15. Global impact of side effects will be assessed using the Functional Assessment of Cancer Therapy (FACT-G) (GP5)
16. Estimate/Confirm established clinically meaningful change scores for clinical outcome assessments (COAs)/domain scores using the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) scales
17. Maximum concentration observed after the first infusion (Cmax) for Belumosudil - Substudy 05
18. Time to reach Cmax (tmax) for Belumosudil - Substudy 05
19. Area under the concentration versus time curve calculated using the trapezoidal method from 0 to 8h (AUC0-8h) for Belumosudil - Substudy 05

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 14

Locations

6 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications