SAR442257 for Multiple Myeloma and Non-Hodgkin Lymphoma

Not currently recruiting at 42 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called SAR442257 for individuals with specific blood cancers: relapsed and refractory multiple myeloma (a cancer of plasma cells) and non-Hodgkin lymphoma (a group of blood cancers in the lymphatic system). The main goal is to identify the highest dose patients can tolerate and determine a suitable dose for future trials. Researchers aim to assess its safety, how it moves through the body, and any signs of cancer-fighting activity. Individuals who have not responded to other treatments for these specific cancers and can identify their condition as relapsed or refractory may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that SAR442257 is likely to be safe for humans?

Research shows that SAR442257 is undergoing its first human trials. It aims to treat relapsed and refractory multiple myeloma and non-Hodgkin lymphoma. The primary goal is to determine the drug's safe dosage.

In earlier studies, some patients with these conditions experienced stable disease or improvement for over eight weeks, suggesting potential benefits of the drug.

However, detailed safety information is not fully available yet, as this is an early study. Early-phase studies like this primarily focus on safety and dosage determination, so researchers closely monitor the treatment for any side effects.

The aim is to ensure SAR442257 is safe and well-tolerated before progressing to larger studies. Participants can expect close monitoring to manage any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for multiple myeloma and non-Hodgkin lymphoma, which often involve chemotherapy or targeted therapies like monoclonal antibodies, SAR442257 is unique because it works by targeting CD38, a protein commonly found on the surface of cancer cells. This mechanism of action is different from many existing therapies and has the potential to offer a more targeted attack on cancer cells, potentially leading to fewer side effects. Researchers are excited about SAR442257 because its novel approach could improve outcomes for patients who have not responded well to current treatments.

What evidence suggests that SAR442257 might be an effective treatment for multiple myeloma and non-Hodgkin lymphoma?

Research has shown that SAR442257, the investigational treatment in this trial, holds promise for people with relapsed and refractory multiple myeloma (RRMM) and non-Hodgkin lymphoma (RR-NHL). In patients with RRMM, 60% experienced disease control, meaning their condition did not worsen for at least 8 weeks. Among those with RR-NHL, one patient showed improvement, and 28.6% had their disease under control. This treatment targets specific proteins on cancer cells to halt their growth. Early results suggest SAR442257 can help manage the disease in some patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1992/531792/First-in-Human-Phase-1-Study-of-SAR442257-in

First-in-Human Phase 1 Study of SAR442257 in Patients with ... In rrNHL cohort, the ORR was 14.3%, 1 pt achieved PR (DOR=7.1 months) at 2 µg/kg BIW TDL. The disease control rate (stable disease or better for > ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124047396

First-in-Human Phase 1 Study of SAR442257 in Patients ... The disease control rate (stable disease or better for >8 weeks) was 60% (n=24) and 28.6% (n=2) in the rrMM and rrNHL cohorts respectively.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10929583/

Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell ... SAR442257 was highly effective in patients relapsing after BCMA therapy. The CD38/CD28xCD3 trispecific format was substantially more effective ...

4. congress.sanofimedical.com congress.sanofimedical.com/s3fs-public/2024-12/First-in-Human%20Phase%201%20Study%20of%20SAR442257%20in%20Patients%20with%20RelapsedRefractory%20Multiple%20Myeloma%20and%20Non-Hodgkin%20Lymphoma.pdf?VersionId=ByFe42OlL.9yJIHe8T0TBTrryeLDb1vC

First-in-Human Phase 1 Study of SAR442257 in Patients with ... ... SAR442257 in Patients with Relapsed/Refractory Multiple Myeloma and ... multiple myeloma; rrNHL, relapsed/refractory non-Hodgkin lymphoma.

5. vjhemonc.com vjhemonc.com/video/uorcbvw5ns4-first-in-human-phase-i-study-of-sar442257-a-tri-specific-antibody-in-rr-multiple-myeloma-and-nhl/

ASH 2024 | First-in-human Phase I Study of SAR442257, a tri ... This study highlights the challenges of this novel therapeutic strategy for multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

6. sanofistudies.com sanofistudies.com/cwout/CW-V9DEXS//us/en/listing/286341/first-in-human-single-agent-study-2/

First-in-human Single Agent Study of SAR442257 in RRMM This study investigates the safety and appropriate dosage of an investigational medication in patients with relapsed and refractory multiple myeloma and non- ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11120574/

Pre-Clinical Assessment of SAR442257, a CD38/CD3xCD28 ... The trispecific antibody SAR442257 shows promise for relapsed/refractory multiple myeloma by enhancing TC activation against tumor cells. 2.