Forimtamig-Based Combinations for Multiple Myeloma

Recruiting at 19 trial locations

Overseen By Reference Study ID Number: BP43437 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Monoclonal antibodies

Disqualifiers: Pregnancy, Plasma cell leukemia, Amyloidosis, Myelodysplastic syndrome, others

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

Compensation: Varies

Number of Visits: Unknown

316 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or in combination with carfilzomib or daratumumab or other combination partners in participants with relapsed or refractory multiple myeloma (r/r MM). The study consists of two phases: a dose exploration phase and a dose-expansion phase.

Will I have to stop taking my current medications?

The trial requires that you stop any prior anti-cancer therapy at least 14 days before starting the study drug. If you have been treated with monoclonal antibodies or antibody-drug conjugates, you must wait 4 weeks or 5 half-lives of the drug, whichever is shorter, before participating.

What data supports the effectiveness of the drug combination Forimtamig-Based Combinations for Multiple Myeloma?

Research shows that combining proteasome inhibitors like carfilzomib with immunomodulatory drugs and monoclonal antibodies, such as daratumumab, has been effective in treating multiple myeloma, improving survival rates and response to treatment. ^{1 2 3 4 5}

What safety information is available for Forimtamig-based treatments for multiple myeloma?

Forimtamig-based treatments, including drugs like Carfilzomib and Daratumumab, have been associated with side effects such as anemia (low red blood cell count), peripheral neuropathy (nerve damage causing pain or numbness), and thromboembolic events (blood clots). These treatments require careful monitoring to manage these potential adverse effects. ^{1 2 6 7 8}

How does the drug Forimtamig differ from other treatments for multiple myeloma?

The research does not provide specific information about Forimtamig, but it highlights that novel treatments for multiple myeloma often involve combinations of immunomodulatory drugs and proteasome inhibitors, which have improved efficacy and manageable side effects. These treatments are designed to target the unique biology of myeloma cells and their environment, offering more personalized and effective options. ^{1 2 3 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for people with relapsed or refractory multiple myeloma who have a good performance status, expect to live at least 12 more weeks, and have recovered from previous cancer treatments. They must have measurable disease progression after their last treatment.

Inclusion Criteria

Life expectancy of at least 12 weeks

Measurable disease

My organs are functioning well.

Exclusion Criteria

I am infected with Hepatitis B.

I have or might have a long-term active Epstein-Barr virus infection.

I have been diagnosed with liver cirrhosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants receive varying doses of forimtamig in combination with daratumumab or carfilzomib to determine optimal dosing until disease progression

Until disease progression

Dose Expansion

Participants receive a fixed dose of forimtamig in combination with daratumumab or carfilzomib until disease progression or completion of 12 months of treatment

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carfilzomib
• Daratumumab
• Forimtamig

Trial Overview The study tests the safety and initial effectiveness of Forimtamig alone or combined with Carfilzomib or Daratumumab in treating multiple myeloma. It has two parts: finding the right dose and then seeing how well it works at that dose.

Participant Groups

Group I: Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab Experimental Treatment 2 Interventions

Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Group II: Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib Experimental Treatment 2 Interventions

Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Group III: Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab Experimental Treatment 2 Interventions

Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Group IV: Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib Experimental Treatment 2 Interventions

Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Group V: Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab Experimental Treatment 2 Interventions

Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Group VI: Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib Experimental Treatment 2 Interventions

Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.

Group VII: Dose Expansion Phase: Forimtamig + Daratumumab Experimental Treatment 2 Interventions

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.

Group VIII: Dose Expansion Phase: Forimtamig + Carfilzomib Experimental Treatment 2 Interventions

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.

Group IX: Dose Expansion Phase: Forimtamig Experimental Treatment 1 Intervention

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase until disease progression or completion of 12 months of treatment, whichever occurs first.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Novel agents like immunomodulatory drugs (IMiDs) and proteasome inhibitors (such as bortezomib) have significantly improved treatment outcomes for myeloma, showing better responses when used in combination with steroids and chemotherapy.

These therapies, initially used for relapsed or refractory myeloma, are now being tested in newly diagnosed patients, leading to higher response rates and longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for multiple myeloma. Dingli, D., Rajkumar, SV.[2009]

Recent advancements in multiple myeloma treatment have introduced several new agents, including pomalidomide, carfilzomib, ixazomib, panobinostat, elotuzumab, and daratumumab, which have transformed treatment strategies over the past five years.

These new agents can be used in various combinations, such as doublets or triplets, and are also integrated into intensive treatment plans involving autologous stem cell transplantation, enhancing the overall management of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat myeloma with new agents. Moreau, P.[2021]

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]

Recent advancements in multiple myeloma treatment have introduced several new drugs that significantly improve patient outcomes, each with unique mechanisms of action and side effect profiles.

The review emphasizes the importance of monitoring and managing specific adverse events associated with these new treatments, providing practical guidance for healthcare providers to enhance patient safety and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Ludwig, H., Delforge, M., Facon, T., et al.[2023]

In a study of 2587 elderly patients with advanced multiple myeloma, those treated with novel agents (proteasome inhibitors and immunomodulatory drugs) had a significantly increased risk of adverse events, including anemia, peripheral neuropathy, and thromboembolic events.

Combination therapies using both proteasome inhibitors and immunomodulatory drugs also showed a higher risk for anemia, neutropenia, and thromboembolic events compared to single-agent therapies, indicating that while these treatments are effective, they come with notable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma. Chen, Y., Lairson, DR., Chan, W., et al.[2018]

The introduction of four novel agents (carfilzomib, elotuzumab, daratumumab, and panobinostat) for treating Multiple Myeloma has significantly improved patient outcomes but also introduced new adverse events that require careful management.

This review emphasizes the importance of recognizing and managing the toxicities associated with these new treatments, based on a comprehensive analysis of clinical trials and recent findings presented at major hematology conferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues and management of toxicities associated with new treatments for multiple myeloma. Brioli, A., Mügge, LO., Hochhaus, A., et al.[2022]

Multiple myeloma is a promising target for immune therapies due to its unique plasma cell biology and bone marrow environment, allowing for treatments that can selectively kill cancer cells with minimal side effects.

Recent advancements in immune therapies, including immune modulatory drugs, targeted antibodies, CAR-T cell therapies, and vaccines, have led to improved treatment options with enhanced effectiveness and specificity against multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. Ackley, J., Ochoa, MA., Ghoshal, D., et al.[2023]

References

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

Emerging therapies for multiple myeloma. [2009]

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

Clinical treatment of newly diagnosed multiple myeloma. [2015]

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

Optimizing Immunomodulatory Drug With Proteasome Inhibitor Combinations in Newly Diagnosed Multiple Myeloma. [2020]

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

How I treat myeloma with new agents. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Risk of adverse events associated with front-line anti-myeloma treatment in Medicare patients with multiple myeloma. [2018]

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

Safety issues and management of toxicities associated with new treatments for multiple myeloma. [2022]

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

Novel therapeutic avenues in myeloma: changing the treatment paradigm. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. [2023]