TTI-622 + Daratumumab for Multiple Myeloma

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

7 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma. The researchers look for the highest dose TTI-622 that causes few or mild side effects in participants when given in combination with daratumumab hyaluronidase-fihj. Once the researchers find the highest safe dose of each study drug, they will further test the combination TTI-622 + daratumumab hyaluronidase-fihj) in new participants to find out if the combinations are effective in treating relapsed/refractory multiple myeloma. Researchers think that combining TTI-621 or TTI-622 with daratumumab hyaluronidase-fihj, a standard treatment for multiple myeloma, may be an effective treatment approach.

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.

What data supports the effectiveness of the drug TTI-622 + Daratumumab for Multiple Myeloma?

Research shows that subcutaneous daratumumab, when combined with hyaluronidase, is effective for multiple myeloma, achieving response rates similar to its intravenous form but with fewer side effects and quicker administration. This suggests that the combination with TTI-622 could also be effective, as daratumumab is already proven to work well in multiple myeloma treatments. ^{1 2 3 4 5}

Is the combination of TTI-622 and Daratumumab safe for humans?

Daratumumab, when given subcutaneously (under the skin), has been shown to be generally safe in patients with multiple myeloma, with common mild side effects like injection-site reactions and some infusion-related reactions. Serious side effects were rare, and the treatment was well tolerated in various studies. ^{1 2 3 4 6}

What makes the drug TTI-622 + Daratumumab unique for treating multiple myeloma?

The combination of TTI-622 with Daratumumab is unique because it involves a subcutaneous formulation of Daratumumab, which allows for a much shorter administration time and lower rates of infusion-related reactions compared to the traditional intravenous method, while maintaining similar efficacy and safety. ^{1 3 4 7 8}

Research Team

Alexander Lesokhin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Subcutaneous delivery of daratumumab in Japanese patients with relapsed/refractory multiple myeloma. [2022]

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

Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of Daratumumab. [2023]

5. England pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]

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

Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma. [2020]

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

Practical Considerations for Antibodies in Myeloma. [2019]

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

Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab. [2020]