A Phase 2 Study of Isatuximab in combination with Pomalidomide and Dexamethasone in MM Patients who received one prior line of therapy containing Lenalidomide and a Proteasome Inhibitor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hellenic Society Of Hematology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Oct 2022 → ongoing

Decision date (initial)

2024-11-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

SANOFI-AVENTIS AEBE

External identifiers

EU CT number

2024-516060-28-00

EudraCT number

2021-004917-38

ClinicalTrials.gov

NCT05298683

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the effect of isatuximab plus pomalidomide and low-dose dexamethasone on the 6-month overall response rate (ORR) in patients with multiple myeloma (MM) who are relapsing for the first time, having previously received one line of treatment that contained lenalidomide and a proteasome inhibitor

Secondary objectives 7

1. 1.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Progression-Free Survival (PFS)
2. 2.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Overall Survival (OS)
3. 3.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Minimal Residual Disease (MRD) negativity rate
4. 4.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Time to Response (TTR)
5. 5.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Duration of Response (DoR)
6. 6.To evaluate the effect of isatuximab in combination with pomalidomide and low-dose dexamethasone on Safety
7. 7.Exploratory: To explore the effect of once-monthly isatuximab plus pomalidomide/low-dose dexamethasone on the PFS of patients who attained ≥ very good partial response (VGPR) after six cycles of treatment with isatuximab Q2W plus pomalidomide/low-dose dexamethasone

Conditions and MedDRA coding

Multiple myeloma patients who received one prior line of therapy containing Lenalidomide and a Proteasome Inhibitor"

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1.Patient has signed an informed consent form (ICF) indicating that he or she understands the purpose of the procedures required for the study and is willing to participate in the study. Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF
2. 2.Male or female patients aged 18 years or older at the time of the ICF signature
3. 3.Patients who have received ONLY one prior line of anti-myeloma therapy, which included lenalidomide (at least 2 cycles, either alone or in combination) and a proteasome inhibitor (e.g. bortezomib, carfilzomib, ixazomib). Patients must have achieved at least a response of MR or better based on the investigator's determination of response as defined by the IMWG criteria. Note 1: An induction treatment followed by ASCT and consolidation/maintenance will be considered as one line of treatment. Note 2: The number of prior lines will be defined according to the guidelines for determination of the number of prior lines of therapy in multiple myeloma (Appendix F)
4. 4.Patients with a documented diagnosis of MM and with current evidence of measurable disease defined as: -Serum monoclonal protein (M-protein) level ≥0.5 g/dL, measured using serum protein electrophoresis (SPEP) and/or -Urine M-protein level ≥200 mg/24 hours, measured using urine protein electrophoresis (UPEP), or -Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
5. 5.Patients must have documented evidence of PD, based on the investigator's determination of response as defined by the IMWG criteria, on or after the last line of treatment
6. 6.Adequate bone marrow and hepatic function as defined by ALL the laboratory criteria : -Absolute Neutrophil Count (ANC) ≥1.0 x 109/L; GCSF administration is not allowed to reach this level -Hemoglobin level ≥7.5 g/dL (≥4.65 mmol/L); -Platelet count ≥75 x 109/L in patients in whom <50% of bone marrow nucleated cells are plasma cells OR Platelet count ≥50 x 109/L in patients in whom ≥50% of bone marrow nucleated cells are plasma cells; [transfusions are not permitted to reach this level] -Alanine aminotransferase (ALT) level ≤2.5 x ULN -Aspartate aminotransferase (AST) level ≤2.5 x ULN -Total bilirubin level ≤1.5 x ULN (except for Gilbert Syndrome: direct bilirubin ≤1.5 x ULN) -Creatinine clearance ≥30 mL/min; calculated using Cockcroft Gault -Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤1.6 mmol/L)
7. 7.Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 (see Appendix B)
8. 8.For patients experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤ Grade 1

Exclusion criteria 20

1. 1.Previous therapy with any anti-CD38 monoclonal antibody within 12 months before C1D1
2. 2.Previous exposure to pomalidomide
3. 3.Patient has received anti-myeloma treatment within two weeks or five pharmacokinetic half-lives of the treatment, whichever is longer, before Cycle 1, Day 1. The only exception is emergency use of a short course of corticosteroids (the equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before C1D1
4. 4.Previous allogeneic stem cell transplant or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1
5. 5.History of malignancy (other than MM) within three years before C1D1
6. 6.Clinical signs of meningeal involvement of MM
7. 7.Clinically significant cardiac disease, including: a) Myocardial infarction within six months before C1D1, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV). b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities. c) Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec
8. 8.Known: a) Active hepatitis A b) To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Patients with resolved infection must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Patients with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. c) To be seropositive for hepatitis C
9. 9.Known to be seropositive for human immunodeficiency virus (defined by positive testing for human immunodeficiency virus (HIV) antibodies)
10. 10.Gastrointestinal disease that may significantly alter the absorption of pomalidomide
11. 11.Patient has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis
12. 12.Any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study
13. 13.Ongoing ≥Grade 2 peripheral neuropathy
14. 14.Patient had ≥Grade 3 rash during prior therapy
15. 15.Patient has had major surgery within two weeks before C1D1, or has not fully recovered from an earlier surgery, or has a surgery planned during the time the patient is expected to participate in the study or within two weeks after the last dose of study drug administration. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery
16. 16.Patient has known allergies, hypersensitivity, or intolerance to any of the study drugs, monoclonal antibodies, human proteins, or their excipients (refer to isatuximab IB) or known sensitivity to mammalianderived products
17. 17.Patient was vaccinated with live vaccines within four weeks prior to C1D1
18. 18.Pregnant or nursing women
19. 19.a. Females of childbearing potential (FCBP) unwilling to prevent pregnancy with the use of two reliable methods of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to five months following the last dose of isatuximab or three months following the last dose of the rest of the study treatment, whichever is longer. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). b. FCBP who are unwilling or unable to be tested for pregnancy: a) before study treatment initiation, b) weekly during 1st month of treatment and then prior to each treatment cycle administration or c) every two weeks in case of irregular menstrual cycles, and d) up to five months following the last dose of isatuximab or three months following the last dose of the rest of the study treatment, whichever is longer
20. 20.Male participants who refuse to practice true abstinence or use a condom during sexual contact with a pregnant female or an FCBP while participating in the study, during dose interruptions and at least five months following the last dose of isatuximab or three months following the last dose of the rest of the study treatment, whichever is longer, even if he has undergone a successful vasectomy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the ORR at six months of treatment with isatuximab in combination with pomalidomide, and low-dose dexamethasone. ORR is defined as the proportion of patients with stringent complete response (sCR), CR, VGPR, and PR, as assessed by the Investigator using the IMWG response criteria (see Appendix A).

Secondary endpoints 6

1. Progression-free survival (PFS) is defined as the time from study treatment initiation (Cycle 1, Day 1) to the day of first documentation of PD, as assessed by the Investigator using the IMWG response criteria (see Appendix A), or the date of death from any cause, or initiation of further anti-myeloma treatment, or data cut-off, whichever occurs first.
2. Overall Survival (OS) is defined as the time from study treatment initiation (Cycle 1, Day 1) to the day of death from any cause. OS will be assessed throughout the treatment period and post EOT during long term follow-up visits until the end of the study.
3. Minimal Residual Disease (MRD) negativity is defined as the proportion of patients achieving MRD-negative status, assessed at suspected CR. Time to Response (TTR) is defined as the time from study treatment initiation (Cycle 1, Day 1) to the day of first objective response of PR or better.
4. Duration of Response (DoR) is defined as the time from the day of the first response, as determined by the Investigator, to the day of first PD (based on the IMWG response criteria, see Appendix A) or death, whichever occurs first. DoR will be determined only for patients who have achieved ≥PR
5. Safety: The incidence of AEs, TEAEs and serious adverse events (SAEs) recorded continuously from ICF until 30 days after last study treatment. AEs and laboratory parameters will be graded using the NCI-CTCAE version 5.0 (see Appendix C) and will be reported in the eCRF
6. Specific safety laboratory tests are planned in case of infusion reaction (see Study Flow Chart in Section 1.2 and Section 10.9.1). Full details of safety reporting and AE monitoring procedures are provided in Section 10.7.2 and Section 10.10.

Investigational products

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

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hellenic Society Of Hematology

Sponsor organisation

Hellenic Society Of Hematology

Address

Kifissias Leoforos 27

City

Athens

Postcode

115 23

Country

Greece

Scientific contact point

Organisation

Hellenic Society Of Hematology

Contact name

Prof. Evangelos Terpos

Public contact point

Organisation

Hellenic Society Of Hematology

Contact name

Prof. Georgios Vasilopoulos

Third parties 6

Locations

1 EU/EEA country · 9 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 11 files

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

Application history

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