Forimtamig-Based Combinations for Multiple Myeloma

No longer recruiting at 20 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and early effects of a new treatment, forimtamig, for individuals with multiple myeloma, a cancer affecting the bone marrow. The trial tests forimtamig alone and with other drugs like carfilzomib (Kyprolis) and daratumumab (Darzalex). It consists of two phases: one to explore different doses and another to assess their expansion and performance. This trial suits those with multiple myeloma whose disease has returned or worsened after previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that forimtamig, a new treatment targeting GPRC5D, is under study to assess its safety and tolerability. Previous patients have demonstrated that it can be used alone or with other drugs like carfilzomib and daratumumab for multiple myeloma, a type of blood cancer. In these studies, researchers tested forimtamig in patients whose cancer returned or didn't respond to earlier treatments.

While detailed safety data is still being collected, early findings suggest that forimtamig is generally well-tolerated, with most people not experiencing severe side effects. However, some side effects can occur, as with any treatment. Researchers are closely monitoring participants to gather more safety information.

Forimtamig is currently in the early stages of testing, focusing on understanding its safety and determining the best dosage. This phase is crucial to ensure the treatment can be administered safely before progressing to larger studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about forimtamig-based treatments for multiple myeloma because they offer new combinations and dosing strategies that could enhance treatment effectiveness. Unlike standard treatments such as lenalidomide, bortezomib, and dexamethasone, forimtamig is being tested in different doses and combined with daratumumab and carfilzomib, which are already known for their potent anti-myeloma effects. This approach could optimize the balance between efficacy and safety. Additionally, the subcutaneous administration of forimtamig may offer a more convenient alternative to intravenous therapies, potentially improving patient comfort and adherence.

What evidence suggests that this trial's treatments could be effective for relapsed or refractory multiple myeloma?

Research has shown that forimtamig alone is promising in treating multiple myeloma, with 66.7% of patients experiencing a reduction or halt in tumor growth. Many patients achieved a very good partial response, indicating significant improvement. In this trial, some participants will receive forimtamig combined with daratumumab, which boosts treatment success and survival, potentially leading to even better results. Other participants will receive forimtamig paired with carfilzomib, which helps patients live longer without disease progression, possibly enhancing outcomes further. These combinations work in different ways to fight cancer, aiming for more effective treatment results. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/2/202/525824/Forimtamig-a-novel-GPRC5D-targeting-T-cell

Forimtamig, a novel GPRC5D-targeting T-cell bispecific ... Despite using 10-fold lower concentration than SoC combinations, forimtamig as a single agent induced lysis of 40% tumor cells after 96 hours. We also observed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11738037/

Forimtamig, a novel GPRC5D-targeting T-cell bispecific ... Forimtamig exhibits superior potency compared with other GPRC5D- and BCMA-targeting TCBs. Forimtamig combination with TCBs and CELMoDs prevents tumor ...

3. targetedonc.com targetedonc.com/view/forimtamig-shows-deep-durable-responses-in-relapsed-refractory-multiple-myeloma

Forimtamig Shows Deep, Durable Responses in Relapsed/ ... At a median duration of response of 12.2 months, the objective response rates with forimtamig across all dose levels was 66.7% with a very good ...

4. nature.com nature.com/articles/s41408-023-00966-9

GPRC5D as a novel target for the treatment of multiple ... Most responders had a very good partial response (VGPR) or better (59% and 57%, respectively). In patients who received prior T-cell–redirection ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37328635/

Bispecific Monoclonal Antibodies in Multiple Myeloma The addition of these agents has significantly improved patient outcomes; however, MM remains largely incurable, with heavily pretreated ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06055075

NCT06055075 | A Study Evaluating Safety, Tolerability, ... The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124108300

Forimtamig, a novel GPRC5D-targeting T-cell bispecific ... Forimtamig is currently being evaluated in phase 1 clinical trials in patients with relapsed and refractory MM for monotherapy and in combination treatments.

8. myeloma.ca myeloma.ca/wp-content/themes/lb-wp-theme/trial/trial/detail.php?study=NCT06055075&lang=

A Study Evaluating Safety, Tolerability, and Clinical Activity ... Summary/Purpose: The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or ...

9. forpatients.roche.com forpatients.roche.com/en/trials/cancer/multiple-myeloma/a-study-evaluating-safety--tolerability--and-clinical-a-92792.html

Clinical trial for Relapsed or Refractory Multiple Myelom... This clinical trial aims to test the safety of forimtamig and forimtamig-based treatment combinations as well as how well they work, and to understand how the ...