TTI-622 + Daratumumab for Multiple Myeloma

Not currently recruiting at 8 trial locations

Overseen By Alexander Lesokhin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Monoclonal antibodies

Disqualifiers: Other malignancies, Autoimmune disorders, Immunodeficiency, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with relapsed or refractory multiple myeloma, a type of blood cancer that has returned or resisted treatment. Researchers are testing the safety of TTI-622 (an experimental treatment) combined with daratumumab hyaluronidase-fihj, aiming to find the highest dose that causes mild or few side effects. Participants who have undergone at least three prior treatments and have not recently used daratumumab hyaluronidase-fihj might be suitable candidates. The trial seeks to determine if this combination can effectively treat the cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you must stop taking your current medications. However, it mentions that treatment with other anti-multiple myeloma therapies must be stopped 14 days before starting the study treatment.

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

Research shows that TTI-622 remains in the early stages of human safety testing. Researchers are primarily determining the safest dose that results in only mild or few side effects.

Daratumumab hyaluronidase-fihj, however, has already received approval as a standard treatment for multiple myeloma. Its safety profile is well-established, and it is generally considered safe for patients with this condition.

The ongoing tests will assess how well people tolerate TTI-622 when combined with daratumumab hyaluronidase-fihj. Although specific safety data for TTI-622 is not yet available, the approval of daratumumab hyaluronidase-fihj suggests some confidence in using these treatments together. However, since TTI-622 is new, researchers are exercising caution and closely monitoring for any serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of TTI-622 and Daratumumab Hyaluronidase-fihj for multiple myeloma because it offers a unique approach compared to existing treatments. TTI-622 is a novel checkpoint inhibitor that targets the CD47-SIRPα pathway, potentially enhancing the immune system's ability to attack cancer cells. Meanwhile, Daratumumab Hyaluronidase-fihj is an anti-CD38 monoclonal antibody that is administered subcutaneously, offering a more convenient delivery method than traditional infusions. This combination might improve the effectiveness of treatment by both directly targeting cancer cells and boosting the body's immune response.

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

Research shows that daratumumab hyaluronidase-fihj, a common treatment for multiple myeloma, targets and destroys cancer cells. In this trial, participants will receive a combination of TTI-622 and daratumumab hyaluronidase-fihj. Studies suggest that TTI-622 might enhance the effect of daratumumab by blocking a protein that usually helps cancer cells evade the immune system. Early evidence indicates that using TTI-622 with daratumumab hyaluronidase-fihj could be more effective against cancer cells than using daratumumab alone. Although research in humans is still ongoing, this combination aims to help the body better attack and reduce multiple myeloma. ^{1 2 3 4 5}

Who Is on the Research Team?

Alexander Lesokhin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory multiple myeloma who have tried at least three prior treatments and meet specific health criteria. They must not have had major surgery or radiation therapy recently, no other cancers, and can't be pregnant or unwilling to use contraception.

Inclusion Criteria

My side effects from previous treatments have mostly gone away.

Women who can have children must have a negative pregnancy test when they are screened for the study.

My liver is working well.

Exclusion Criteria

I have not had a heart attack or stroke in the last 6 months.

I do not have any severe medical or mental health issues currently.

I have not had radiation therapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

TTI-622 and daratumumab hyaluronidase-fihj are administered to determine the highest safe dose and evaluate effectiveness

8 weeks

Weekly administration

Dose Escalation

Participants receive TTI-622 and daratumumab hyaluronidase-fihj with dose adjustments based on safety and tolerability

4 weeks

Weekly administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab Hyaluronidase-fihj
• TTI-622

Trial Overview The study tests the safety of TTI-622 combined with daratumumab hyaluronidase-fihj to find the highest dose that's safe with few side effects. After determining this dose, its effectiveness in treating multiple myeloma will be evaluated.

How Is the Trial Designed?

Group I: TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj Experimental Treatment 2 Interventions

TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter.

Group II: TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj Experimental Treatment 2 Interventions

TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Trillium Therapeutics Inc.

Industry Sponsor

Trials

7

Recruited

620+

Published Research Related to This Trial

Daratumumab received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

Daratumumab, now available in a subcutaneous form, significantly reduces administration time from 7 hours to just 3-5 minutes compared to the intravenous version, making it more convenient for patients.

The subcutaneous formulation also has lower rates of infusion-related reactions (less than 10% compared to 50% for intravenous), while maintaining similar efficacy and safety profiles, which enhances its overall usability in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. Sanchez, L., Richter, J., Cho, HJ., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05139225

NCT05139225 | A Study of TTI-622 in Combination With ... This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma.

2. cancer.gov cancer.gov/clinicaltrials/NCI-2021-13407

A Study of TTI-622 in Combination with Daratumumab ... This phase Ib trial test the safety and best dose of TTI-622 in combination with daratumumab hyaluronidase-fihj in treating patients with multiple myeloma.

3. sparkcures.com sparkcures.com/trial/1231/nct05139225

Multiple Myeloma Support + Trials This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma.

4. withpower.com withpower.com/trial/phase-1-multiple-myeloma-9-2021-52fbe

TTI-622 + Daratumumab for Multiple Myeloma · Info for Participants This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05139225/a-study-of-tti-622-in-combination-with-daratumumab-hyaluronidase-fihj-in-people-with-multiple-myeloma?activelyRecruiting=false&page=86&id=841&slug=bone-neoplasm

A Study of TTI-622 in Combination With Daratumumab ... This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple ...