SAR650984, Pomalidomide and Dexamethasone in Combination in RRMM Patients (PomdeSAR)

A Phase 1b Study of SAR650984 (Isatuximab) in Combination With Pomalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma

Primary Objectives:

Part A: To evaluate the safety and determine the recommended dose of SAR650984 in combination with pomalidomide (P) and dexamethasone (d), in patients with Relapsed/Refractory Multiple Myeloma (RRMM).

Part B: To evaluate the feasibility of isatuximab administered from a fixed infusion volume in combination with Pd as assessed by occurrence of grade ≥3 infusion associated reactions (IAR).

Secondary Objectives:

• To evaluate the infusion duration (Part B).
• To evaluate the safety profile of the combination with isatuximab administration from fixed volume (Part B).
• To evaluate immunogenicity of SAR650984 in combination with Pd (Part A and B).
• To evaluate the pharmacokinetics (PK) of SAR650984 and its effect on the PK of pomalidomide when administered in combination (Part A).
• To describe the efficacy of the combination of SAR650984 with Pd in terms of overall response rate and clinical benefit rate based on International Myeloma Working Group (IMWG) defined response criteria and the duration of response (Part A and B).
• To assess the relationship between clinical effects (adverse event [AE] and/or tumor response) and CD38 receptor density at baseline (Part A).

Study Overview

• Status: Completed
• Conditions: Plasma Cell Myeloma
• Intervention / Treatment: Drug: Dexamethasone; Drug: Isatuximab SAR650984; Drug: Pomalidomide

Detailed Description

The study duration for an individual patient will include a screening period for inclusion of up to 21 days. The treatment period may continue until disease progression, unacceptable adverse reaction, or other reason for discontinuation. After study treatment discontinuation an end of treatment (EOT) visit will be done at approximately 30 days after last study treatment component administration to assess safety. If the last ADA sample is positive or inconclusive, additional ADA will be sampled 3 months later. No further ADA will be sampled, even if this 3-month sample is positive. Patients who discontinue treatment for reasons other than progression of disease will be followed every month until progression or initiation of subsequent therapy, for a maximum of one year, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85054
      • Investigational Site Number 840001
  • California
    • Duarte, California, United States, 91010
      • Investigational Site Number 840006
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8017
      • Investigational Site Number 840018
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Investigational Site Number 840011
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 840004
    • Boston, Massachusetts, United States, 2114
      • Investigational Site Number 840104
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Investigational Site Number 840010
    • Charlotte, North Carolina, United States, 28204
      • Investigational Site Number 840003
  • Ohio
    • Canton, Ohio, United States, 44718
      • Investigational Site Number 840014
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Investigational Site Number 840016
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Investigational Site Number 840015
  • Washington
    • Seattle, Washington, United States, 98108
      • Investigational Site Number 840005
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Investigational Site Number 840017

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Patient has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
• Patient had received at least two previous therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on therapy or after completion of the last therapy.

• Patients with measurable disease 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 free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).

Exclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status >2.
• Poor bone marrow reserve.
• Poor organ function.
• Known intolerance/hypersensitivity to IMiDs, dexamethasone, boron or mannitol, sucrose, histidine or polysorbate 80.
• Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the Investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results.
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PomdeSAR; Part A: Isatuximab (escalating dose) on Day 1, 8, 15, and 22, then Day 1 and 15 + pomalidomide 4 mg on Day 1 to 21 + dexamethasone 40 mg (20 mg in patients of 75 years or older) on Day 1, 8, 15, 22 in 28-day cycles up to disease progression Part B: Isatuximab 10 mg/kg on Day 1, 8, 15, and 22, then Day 1 and 15 + pomalidomide 4 mg on Day 1 to 21 + dexamethasone 40 mg (20 mg in patients of 75 years or older) on Day 1, 8, 15, 22 in 28-day cycles up to disease progression

Drug: Dexamethasone; Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous; Drug: Isatuximab SAR650984; Pharmaceutical form:solution for infusion Route of administration: intravenous; Other Names: Sarclisa; Drug: Pomalidomide; Pharmaceutical form:capsules Route of administration: oral; Other Names: Pomalyst

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicities (DLTs)	Part A: Up to 4 weeks
Number of patients with adverse events and clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling	Part A: Up to 30 days for patients experiencing progressive disease and up to one year or the initiation of a new line of treatment for patients leaving the study for reasons other than progressive disease
Incidence of grade ≥3 IARs according to the NCI-CTC version 4.03 grade scaling	Part B: Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate	Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Pharmacokinetics: Partial area under the serum concentration time curve (AUC)	Part A: Up to approximately 10 months
Pharmacokinetics: maximum observed concentration (Cmax)	Part A: Up to approximately 10 months
Immune response: levels of human anti-human antibodies (ADA)	Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Duration of response - Time	Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Clinical Benefit rate	Part A: Up to approximately 8 months; Part B: Up to approximately 10 months
Infusion duration	Part B: Up to approximately 10 months
Safety of isatuximab administration from fixed volume	Part B: Up to 30 days for patients experiencing progressive disease and up to one year or the initiation of a new line of treatment for patients leaving the study for reasons other than progressive disease
Relationship between clinical effect and CD38 receptor density	Part A: Up to approximately 8 months

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Mikhael J, Belhadj-Merzoug K, Hulin C, Vincent L, Moreau P, Gasparetto C, Pour L, Spicka I, Vij R, Zonder J, Atanackovic D, Gabrail N, Martin TG, Perrot A, Bensfia S, Weng Q, Brillac C, Semiond D, Mace S, Corzo KP, Leleu X. A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab. Blood Cancer J. 2021 May 12;11(5):89. doi: 10.1038/s41408-021-00478-4. No abstract available.
• Usmani SZ, Karanes C, Bensinger WI, D'Souza A, Raje N, Tuchman SA, Sborov D, Laubach JP, Bianchi G, Kanagavel D, Saleem R, Dubin F, Campana F, Richardson PG. Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma. Leukemia. 2021 Dec;35(12):3526-3533. doi: 10.1038/s41375-021-01262-w. Epub 2021 May 28.
• Mikhael J, Richardson P, Usmani SZ, Raje N, Bensinger W, Karanes C, Campana F, Kanagavel D, Dubin F, Liu Q, Semiond D, Anderson K. A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Blood. 2019 Jul 11;134(2):123-133. doi: 10.1182/blood-2019-02-895193. Epub 2019 Mar 12.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2015
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: November 3, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Anti-CD38 monoclonal antibody
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide
• Other Study ID Numbers: TCD14079; U1111-1155-7484 (Other Identifier: UTN)