A clinical trial to look at how safe forimtamig-based treatment combinations are and how well they work in people with relapsed or refractory multiple myeloma

1. Why is the BP43437 clinical trial needed?

Multiple myeloma (MM) is a cancer that forms in plasma cells – a type of white blood cell, that gather in the bone marrow. Although there are many treatment options for people diagnosed with multiple myeloma, patients often see their cancer return after their first treatment (relapsed MM), or the cancer does not respond to treatment (refractory MM). Two standard treatments for people with relapsed or refractory MM (RRMM) are carfilzomib and daratumumab. While these medicines work well, they may not work for all patients and additional treatment options are needed. Forimtamig is a type of drug called a T-cell bispecific antibody. It works by attaching to certain proteins on myeloma cells as well as cells in the immune system, which brings them closer together to help the immune system destroy the myeloma cells. Researchers hope that combining forimtamig with carfilzomib or daratumumab will improve health outcomes for people with RRMM.

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 body processes them.

2. How does the BP43437 clinical trial work?

This clinical trial is recruiting people with RRMM. People who take part in this clinical trial (participants) may be given the clinical trial treatment forimtamig alone for up to 1 year, or forimtamig with either carfilzomib or daratumumab for up to 1 year. Participants will have the option to continue treatment with carfilzomib or daratumumab only, after this time, for as long as it benefits them. The clinical trial doctor will see them regularly to check how they respond to the treatment and any side effects they may have. Participants will need to stay overnight in the hospital for monitoring after receiving the first three doses of forimtamig. The total time of participation in the clinical trial will be about 2 years. Participants can stop trial treatment and leave the clinical trial at any time.

3. What are the main endpoints of the BP43437 clinical trial?

The main clinical trial endpoints (the main results measured in the trial to see if the drug has worked) are:

• The number of participants with no or reduced cancer after treatment (objective response rate)
• The number of participants with no signs of cancer on scans or tests (complete response rate)
• The number of participants with at least a 90% improvement in their disease (very good partial response)
• The number and seriousness of any side effects

The other clinical trial endpoints include:

• The amount of time between the start of the trial and participants’ cancer getting worse (progression-free survival)
• The amount of time between participants’ cancer getting better from treatment and then getting worse (duration of response)
• How long participants live (overall survival), the amount of time between the start of the trial to cancer first getting better, and to the best response to treatment
• How the body processes forimtamig alone and in combination and how it affects the immune system

4. Who can take part in this clinical trial?

People can take part in this trial if they are at least 18 years old, diagnosed with RRMM and agree to have a small sample of bone marrow taken (biopsy). People may not be able to take part in this trial if they have previously received certain cancer treatments, are pregnant or breastfeeding, or have a history of autoimmune disease, severe allergies or certain other medical conditions.

5. What treatment will participants be given in this clinical trial?

Everyone who joins this clinical trial will be enrolled in either the exploration phase or the expansion phase. Participants will be placed at random (by chance) into 1 of 3 treatment groups they fit the criteria for that are open. Treatment will be given in 28-day cycles - a treatment cycle is the number of days it takes to administer the treatment, complete any follow-up that is required and provide a rest before the start of the next round of treatment – as follows:

• Group A – forimtamig alone
• Group B – forimtamig plus carfilzomib
• Group C – forimtamig plus daratumumab
• Forimtamig is given as an injection under the skin (also called a subcutaneous injection) using three step-up (increasing) doses during the first 2 weeks. From Cycle 2, participants will receive forimtamig every 2 weeks
• Carfilzomib is given as an infusion (into the vein) on Day 1, 8, and 15 from Cycle 2
• Daratumumab is given as a subcutaneous injection on Days 1, 8, 15 and 22 in Cycles 1 and 2, on Day 1 and 15 in Cycles 3–6 and on Day 1 from Cycle 7 onwards

After the exploration phase more participants may be included in the expansion phase. If a participant experiences a potential side effect called ‘cytokine release syndrome’ (when the immune system releases large amounts of inflammatory substances throughout the body), they may have to stay in the hospital for a longer period to be monitored and may be given tocilizumab as an infusion (into the vein).

6. Are there any risks or benefits in taking part in this clinical trial?

The safety or effectiveness of the study drug or its use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).

Risks associated with the clinical trial drugs

Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly. Participants will be told about the known side effects of forimtamig, carfilzomib, daratumumab, and tocilizumab and possible side effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known side effects of infusion and subcutaneous injections.

Potential benefits associated with the clinical trial

Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.