SAR442257 for Multiple Myeloma and Non-Hodgkin Lymphoma

Recruiting at 39 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sanofi

Must not be taking: Anticoagulants, Corticosteroids

Disqualifiers: Other malignancy, CNS disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 16 months

47 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests SAR442257, a new drug, in patients with hard-to-treat multiple myeloma and non-Hodgkin lymphoma. It aims to find the highest safe dose and see if the drug can shrink tumors.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor to get a clear answer based on your specific situation.

What data supports the effectiveness of the treatment SAR442257 for Multiple Myeloma?

Research suggests that targeting CD229, a molecule found on the surface of myeloma cells, could be effective in treating multiple myeloma. CD229 is highly expressed on chemotherapy-resistant cells, and therapies targeting it may help eliminate these cells, potentially leading to longer remissions or cures. ^{1 2 3 4 5}

What makes the drug SAR442257 unique for treating multiple myeloma and non-Hodgkin lymphoma?

SAR442257 is unique because it targets CD229, a molecule found on the surface of multiple myeloma cells, including those that are resistant to chemotherapy. This approach aims to eliminate both the bulk of tumor cells and the chemotherapy-resistant cells, potentially leading to longer remissions or even cures. ^{1 6 7 8 9}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

Adults with relapsed and refractory multiple myeloma (RRMM) or non-Hodgkin lymphoma (RR-NHL), who have tried at least three prior therapies including specific agents, are not responding to certain treatments, and have measurable disease. They should be in stable condition with a life expectancy of at least 12 weeks, an ECOG performance status ≤2, no severe heart issues, and willing to use contraception.

Inclusion Criteria

I have advanced cutaneous T cell lymphoma with no standard treatment options left.

My condition is a type of T cell lymphoma.

I have been diagnosed with diffuse large B-cell lymphoma.

Exclusion Criteria

I do not have an ongoing infection needing treatment now or in the last 14 days.

Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

SAR442257 is administered intravenously with lead-in doses in the first week, followed by once weekly until week 4 (Cycle 1) and once weekly for each subsequent cycle(s).

4 weeks for Cycle 1, 28 days for subsequent cycles

Treatment

Participants receive SAR442257 to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).

up to 16 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and pharmacokinetic parameters.

30 days after end of treatment

Treatment Details

Interventions

• SAR442257

Trial Overview The trial is testing SAR442257 as a single agent to find the highest dose patients can tolerate without severe side effects (MTD) for RRMM and RR-NHL. It will also determine the recommended Phase 2 dose (RP2D), study its safety profile, how it moves through the body (pharmacokinetics), potential immune response against it (immunogenicity), and initial signs of effectiveness against tumors.

Participant Groups

Group I: Dose escalation Experimental Treatment 1 Intervention

SAR442257 will be given intravenously with lead-in doses (LID) in the first-week, followed by once weekly until week 4 (Cycle 1) and once weekly for each subsequent cycle(s).

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

CD229 is highly overexpressed on various plasma cell subtypes, including those in patients with Multiple Myeloma (MM) and related conditions, indicating its potential as a therapeutic target.

Targeting CD229 could effectively address both the bulk tumor cells and the chemotherapy-resistant cells in the bone marrow, potentially leading to longer remissions or cures for MM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma. Yousef, S., Kovacsovics-Bankowski, M., Salama, ME., et al.[2018]

High-dose therapy with autologous hematopoietic stem cell transplant has shown to be superior to conventional therapy for multiple myeloma, achieving complete remission rates of 25-30% and median survival exceeding 5 years.

Conventional therapies have seen minimal improvement over the past 20-30 years, with only 5% of patients achieving complete response and a median survival of around 36 months, highlighting the need for newer treatment strategies currently in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple myeloma: an old disease with new hope for the future. Zaidi, AA., Vesole, DH.[2019]

Over 20 years of research and analysis of more than 1000 multiple myeloma genomes have led to a better understanding of the disease's development and potential treatment targets.

The review emphasizes the need to translate genetic and biological insights into clinical practice, suggesting a framework for using targeted therapies and risk stratification to enhance patient management in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Bench to Bedside: The Evolution of Genomics and Its Implications for the Current and Future Management of Multiple Myeloma. Morgan, GJ., Boyle, EM., Davies, FE.[2021]

CD229 CAR T cells have shown strong activity against multiple myeloma (MM) plasma cells and related cells in both laboratory and animal studies, suggesting they could be a promising treatment option for this challenging cancer.

Importantly, CD229 CAR T cells do not harm normal T cells during production, as they selectively target MM cells while sparing functional T cells that express low or no CD229, which may enhance safety in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Radhakrishnan, SV., Luetkens, T., Scherer, SD., et al.[2021]

In a study of 44 patients with multiple myeloma, the two-dose SARS-CoV-2 mRNA vaccination showed low rates of adverse reactions, similar to those seen in general vaccine trials.

A high percentage of patients (93% on therapy and 94% not on therapy) developed detectable antibodies after the second dose, indicating strong immunogenicity and providing reassurance for vaccine-hesitant patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma. Greenberg, RS., Ruddy, JA., Boyarsky, BJ., et al.[2023]

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Evolution of diagnostic workup and treatment for multiple myeloma 2013-2019. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Multiple myeloma: an old disease with new hope for the future. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

From Bench to Bedside: The Evolution of Genomics and Its Implications for the Current and Future Management of Multiple Myeloma. [2021]

5. Italy pubmed.ncbi.nlm.nih.gov

Outcome and survival of myeloma patients diagnosed 2008-2015. Real-world data on 4904 patients from the Swedish Myeloma Registry. [2019]

6. England pubmed.ncbi.nlm.nih.gov

CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with multiple myeloma. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. [2023]